TREA

Condensed heterocylic compounds and herbicides containing them

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Information

  • Patent Grant
  • 6586368
  • Patent Number
    6,586,368
  • Date Filed
    Wednesday, February 7, 2001
    23 years ago
  • Date Issued
    Tuesday, July 1, 2003
    21 years ago
Information
Abstract
Condensed heterocyclic compounds of general formula (I) wherein T is carbon or nitrogen; when T is carbon, then the bond between T and A is a double bond, the bond between A and Y is a single bond, and Y is oxygen, sulfur, or optionally substituted NH; or when T is nitrogen, then the bond between T and A is a single bond, the bond between A and Y is a double bond, and Y is nitrogen or optionally substituted CH; A is nitrogen or optionally substituted CH; R1 is hydrogen, halogen, alkyl, haloalkyl, hydroxymethyl, nitro, or cyano; R2 is hydrogen, halogen, alkyl, haloalkyl, hydroxymethyl, nitro, cyano, or the like; R3 is hydrogen, halogen, alkyl, haloalkyl, hydroxymethyl, nitro, cyano, or the like; R4 is hydrogen, halogen, alkyl, halo-alkyl, hydroxymethyl, nitro, or cyano; and Q is a saturated or unsaturated 5- or 6- membered heterocyclic ring containing one to four nitrogen atoms, or a saturated or unsaturated cyclopentylideneamino group containing one or two nitrogen heteroatoms and one oxygen or sulfur heteroatom.
Description




TECHNICAL FIELD




The present invention relates to condensed heterocyclic compounds and their use.




DISCLOSURE OF THE INVENTION




The present inventors have extensively studied to find compounds having excellent herbicidal activity. As a result, they have found that the condensed heterocyclic compounds of general formula I as depicted below have excellent herbicidal activity, thereby completing the present invention.




The present invention provides condensed heterocyclic compounds of general formula I:











(hereinafter referred to as the present compounds)




wherein T is carbon or nitrogen; when T is carbon, then the bond between T and A is a double bond, the bond between A and Y is a single bond, and Y is oxygen, sulfur, or N—R


142


; or when T is nitrogen, then the bond between T and A is a single bond, the bond between A and Y is a double bond, and Y is nitrogen or C—R


152


;




wherein R


142


is hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


6


alkenyl, C


3


-C


6


alkynyl, cyano, —COR


143


, —N(R


145


)R


146


, or —N═C(R


147


)R


148


; R


152


is hydrogen, halogen, C


1


-C


3


alkyl, nitro, amino, cyano, or —COR


153


;




 wherein R


143


is hydrogen, C


1


-C


3


alkyl, C


1


-C


3


haloalkyl, hydroxyl, C


1


-C


5


alkoxy, or —N(R


156


)N


157


; R


145


and R


146


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, formyl, (C


1


-C


5


alkyl)carbonyl, (C


1


-C


5


haloalkyl)carbonyl, or (C


1


-C


6


alkoxy)carbonyl; R


147


and R


148


are independently hydrogen or C


1


-C


5


alkyl; R


153


is hydrogen, C


1


-C


3


alkyl, C


1


-C


3


haloalkyl, hydroxyl, C


1


-C


5


alkoxy, or —N(R


154


)R


155


;




wherein R


156


and R


157


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, formyl, (C


1


-C


5


alkyl)carbonyl, (C


1


-C


5


haloalkyl)carbonyl, or (C


1


-C


5


alkoxy)carbonyl; R


154


and R


155


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, (C


1


-C


5


alkoxy)carbonyl, formyl, (C


1


-C


5


alkyl)carbonyl, or (C


1


-C


5


haloalkyl)carbonyl;




A is nitrogen or C—R


141


wherein R


141


is hydrogen, halogen, or C


1


-C


3


alkyl;




R


1


is hydrogen, halogen, C


1


-C


3


alkyl, C


1


-C


3


haloalkyl, hydroxymethyl, nitro, or cyano;




R


2


is hydrogen, halogen, C


1


-C


11


alkyl, C


1


-C


11


haloalkyl, hydroxymethyl, nitro, cyano, —N(R


9


)R


10


, —OR


11


, —SR


12


, —SO


2


R


13


, —COX, —COOR


14


, —CON(R


15


)R


16


, —COR


17


, —C(R


26


)═NOR


19


, —C(R


27


)═C(R


21


)R


22


, or —CH(R


23


)—CH(R


24


)R


25


;




R


3


is hydrogen, halogen, C


1


-C


11


alkyl, C


1


-C


11


haloalkyl, hydroxymethyl, nitro, cyano, —N(R


59


)R


60


, —OR


61


, —SR


62


, —SO


2


R


63


, —COX, —COOR


64


, —CON(R


65


)R


66


, —COR


67


, —C(R


76


)═NOR


69


, —C(R


77


)═C(R


71


)R


72


, or —CH(R


73


)—CH(R


74


)R


75


;




R


4


is hydrogen, halogen, C


1


-C


3


alkyl, C


1


-C


3


haloalkyl, hydroxymethyl, nitro, or cyano;




 wherein X is chlorine or bromine;




R


9


and R


59


are independently hydrogen, C


1


-C


5


alkyl, (C


1


-C


5


alkyl)carbonyl, or (C


1


-C


5


alkoxy)carbonyl;




R


10


, R


11


, and R


12


are independently hydrogen, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, C


3


-C


10


cycloalkyl, C


3


-C


10


halocycloalkyl, C


3


-C


10


cycloalkyl C


1


-C


3


alkyl, C


3


-C


10


alkenyl, C


3


-C


10


haloalkenyl, C


3


-C


10


alkynyl, C


3


-C


10


haloalkynyl, cyano C


1


-C


6


alkyl, (C


1


-C


5


alkyl)carbonyl, (C


1


-C


5


haloalkyl)carbonyl, (C


3


-C


10


cycloalkyl)carbonyl, (C


1


-C


5


alkyl)carbonyl, C


1


-C


5


alkyl, (C


1


-C


5


haloalkyl)carbonyl C


1


-C


5


alkyl, hydroxy C


1


-C


5


alkyl, C


1


-C


5


alkoxy C


1


-C


5


alkyl, C


1


-C


5


alkylthio C


1


-C


5


alkyl, (C


1


-C


5


alkoxy)carbonyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl, —C(R


43


)(R


44


)—C(═O)ON(R


45


)R


46


, —C(R


47


)(R


48


) —CON(R


49


)R


50


, —CH


2


—C(R


56


)═NOR


55


, —CHMe—C(R


58


)═NOR


57


, (C


3


-C


10


alkenoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkynoxy)carbonyl C


1


-C


5


alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy (C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkenoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkynoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, carboxy(C


1


-C


5


alkyl)carbonyl, (C


1


-C


10


alkoxy)carbonyl(C


1


-C


5


alkyl)carbonyl, (C


1


-C


10


haloalkoxy)carbonyl(C


1


-C


5


alkyl)carbonyl, C


1


-C


5


alkylsulfonyl, C


1


-C


5


haloalkylsulfonyl, —SO


2


N(R


51


)R


52


, —CON(R


53


)R


54


, optionally substituted benzyl, or optionally substituted phenyl;




R


60


, R


61


, and R


62


are independently hydrogen, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, C


3


-C


10


cycloalkyl, C


3


-C


10


halocycloalkyl, C


3


-C


10


cycloalkyl C


1


-C


3


alkyl, C


3


-C


10


alkenyl, C


3


-C


10


haloalkenyl, C


3


-C


10


alkynyl, C


3


-C


10


haloalkynyl, cyano C


1


-C


6


alkyl, (C


1


-C


5


alkyl)carbonyl, (C


1


-C


5


haloalkyl)carbonyl, (C


3


-C


10


cycloalkyl)carbonyl, (C


1


-C


5


alkyl)carbonyl C


1


-C


5


alkyl, (C


1


-C


5


haloalkyl)carbonyl C


1


-C


5


alkyl, hydroxy C


1


-C


5


alkyl, C


1


-C


5


alkoxy C


1


-C


5


alkyl, C


1


-C


5


alkylthio C


1


-C


5


alkyl, (C


1


-C


5


alkoxy)carbonyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


10


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl, —C(R


163


)(R


164


)—C(═O)ON(R


165


)R


166


, —C(R


167


)R


168


)—CON(R


169


)R


170


, —CH


2


—C(═NOR


175


)R


176


, —CHMe—C(═NOR


177


)R


178


, (C


3


-C


10


alkenoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkynoxy)carbonyl C


1


-C


5


alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkenoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkynoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl, carboxy(C


1


-C


5


alkyl)carbonyl, (C


1


-C


110


alkoxy)carbonyl(C


1


-C


5


alkyl)carbonyl, (C


1


-C


10


haloalkoxy)carbonyl(C


1


-C


5


alkyl)carbonyl, C


1


-C


5


alkylsulfonyl, C


1


-C


5


haloalkylsulfonyl, —SO


2


N(R


171


)R


172


, —CON(R


173


)R


174


, optionally substituted benzyl, or optionally substituted phenyl;




 wherein R


43


, R


44


, R


163


, and R


164


are independently hydrogen, halogen, C


1


-C


5


alkyl, or C


1


-C


5


haloalkyl;




R


45


, R


46


, R


165


, and R


166


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; or R


45


and R


46


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring, or R


165


and R


166


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring;




R


47


, R


48


, R


167


, and R


168


are independently hydrogen, halogen, C


1


-C


5


alkyl, or C


1


-C


5


haloalkyl;




R


49


, R


50


, R


169


, and R


170


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; or R


49


and R


50


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R


169


and R


170


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;




R


51


, R


52


, R


171


, and R


172


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; or R


51


and R


52


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R


171


and R


172


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;




R


53


, R


54


, R


173


, and R


174


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; or R


53


and R


54


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R


173


and R


174


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated, ring containing zero to one oxygen atom or NH group in the ring;




R


55


, R


57


, R


175


, and R


177


are independently hydrogen or C


1


-C


3


alkyl;




R


56


, R


58


, R


176


, and R


178


are independently hydrogen, C


1


-C


5


alkyl, (C


1


-C


5


alkoxy)carbonyl, (C


1


-C


5


haloalkoxy)carbonyl, (C


3


-C


5


cycloalkoxy)carbonyl, (C


3


-C


5


alkenoxy)carbonyl, or (C


3


-C


5


alkynoxy)carbonyl;




R


13


is hydroxy, chlorine, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl, —N(R


79


)R


80


, or —OR


81


;




R


63


hydroxy, chlorine, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl, —N(R


179


)R


180


, or —OR


181


;




 wherein R


79


and R


179


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, C


3


-C


6


alkynyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, or (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl; R


80


and R


180


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; or R


79


and R


80


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R


179


and R


180


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; and R


81


and R


181


are independently C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, C


3


-C


6


alkynyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, or (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl;




R


14


is hydrogen, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, C


3


-C


10


cycloalkyl, C


3


-C


10


halocycloalkyl, C


3


-C


10


cycloalkyl C


1


-C


3


alkyl, C


3


-C


10


alkenyl, C


3


-C


10


haloalkenyl, C


3


-C


10


alkynyl, C


3


-C


10


haloalkynyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkenoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkynoxy)carbonyl C


1


-C


5


alkyl, —N(R


82


)R


83


, optionally substituted benzyl, or optionally substituted phenyl;




R


64


is hydrogen, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, C


3


-C


10


cycloalkyl, C


3


-C


10


halocycloalkyl, C


3


-C


10


cycloalkyl C


1


-C


3


alkyl, C


3


-C


10


alkenyl, C


3


-C


10


haloalkenyl, C


3


-C


10


alkynyl, C


3


-C


10


haloalkynyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkenoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


alkynoxy)carbonyl C


1


-C


5


alkyl, —N(R


182


)R


183


, optionally substituted benzyl, or optionally substituted phenyl;




 wherein R


82


and R


182


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, C


3


-C


6


alkynyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, or (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl; R


83


and R


183


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; or R


82


and R


83


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R


182


and R


183


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;




R


15


and R


65


are independently hydrogen, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, C


3


-C


10


cycloalkyl, C


3


-C


10


cycloalkyl C


1


-C


3


alkyl, C


3


-C


10


alkenyl, C


3


-C


10


alkynyl, cyano C


1


-C


6


alkyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, optionally substituted benzyl, or optionally substituted phenyl; R


16


and R


66


are independently hydrogen, C


1


-C


10


alkyl, or C


1


-C


10


haloalkyl; or R


15


and R


16


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R


65


and R


66


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;




R


17


, R


26


, R


27


, R


67


, R


76


, and R


77


are independently hydrogen, cyano, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, C


3


-C


10


cycloalkyl, C


3


-C


10


cycloalkyl C


1


-C


3


alkyl, (C


1


-C


6


alkoxy)carbonyl, or (C


1


-C


6


alkoxy)carbonylmethyl;




R


19


and R


69


are independently hydrogen, C


1


-C


10


alkyl, C


1


-C


10


haloalkyl, C


3


-C


10


cycloalkyl, C


3


-C


10


halocycloalkyl, C


3


-C


10


cycloalkyl C


1


-C


3


alkyl, C


3


-C


10


alkenyl, C


3


-C


10


haloalkenyl, C


3


-C


10


alkynyl, C


3


-C


10


haloalkynyl, cyano C


1


-C


6


alkyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, or (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl;




R


21


and R


71


are independently hydrogen, halogen, C


1


-C


3


alkyl, or C


1


-C


3


haloalkyl;




R


22


and R


25


are independently carboxy, (C


1


-C


10


alkoxy)carbonyl, (C


1


-C


10


haloalkoxy)carbonyl, (C


3


-C


10


cycloalkoxy)carbonyl, (C


3


-C


10


halocycloalkoxy)carbonyl, carboxy(C


1


-C


5


alkoxy)carbonyl, (C


1


-C


10


alkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, (C


1


-C


10


haloalkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, (C


3


-C


10


cycloalkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, (C


3


-C


10


alkenoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, (C


3


-C


10


alkynoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, —CON(R


84


)R


85


, or —C(═O)ON(R


86


)R


87


;




R


72


and R


75


are independently carboxy, (C


1


-C


10


alkoxy)carbonyl, (C


1


-C


10


haloalkoxy)carbonyl, (C


3


-C


10


cycloalkoxy)carbonyl, (C


3


-C


10


halocycloalkoxy)carbonyl, carboxy(C


1


-C


5


alkoxy)carbonyl, (C


1


-C


10


alkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, (C


1


-C


10


haloalkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, (C


3


-C


10


cycloalkoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, (C


3


-C


10


alkenoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, (C


3


-C


10


alkynoxy)carbonyl (C


1


-C


5


alkoxy)carbonyl, —CON(R


184


R


185


, or —C(═O)ON(R


186


)R


187


;




 wherein R


84


and R


184


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, C


3


-C


6


alkynyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl, (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, or (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl; R


85


and R


185


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; or R


84


and R


85


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R


184


and R


185


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;




R


86


and R


186


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, C


3


-C


6


alkynyl, carboxy C


1


-C


5


alkyl, (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl, (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl, or (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl; R


87


and R


187


are independently hydrogen, C


1


-C


5


alkyl, C


1


-C


5


haloalkyl, C


3


-C


8


cycloalkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; or R


86


and R


87


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; or R


186


and R


187


may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring;




R


23


, R


24


, R


73


, and R


74


are independently hydrogen, halogen, C


1


-C


3


alkyl, or C


1


-C


3


haloalkyl; and




Q is any one group of Q1 to Q23 of the general formula:



























 wherein:




in Q1, E


1


and E


2


are independently C


1


-C


6


alkyl optionally substituted with halogen, or C


3


-C


6


cycloalkyl optionally substituted with halogen; or E


1


and E


2


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen;




in Q2, E


3


and E


4


are independently C


1


-C


6


alkyl optionally substituted with halogen, or C


3


-C


6


cycloalkyl optionally substituted with halogen; or E


3


and E


4


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; D


1


and D


2


are independently oxygen or sulfur; and Z


1


is nitrogen or CH;




in Q3, E


5


is hydrogen or C


1


-C


6


alkyl optionally substituted with halogen; and D


3


is oxygen or sulfur;




in Q4, E


6


and E


7


are independently hydrogen, C


1


-C


6


alkyl optionally substituted with halogen, or C


3


-C


6


cycloalkyl optionally substituted with halogen; or E


6


and E


7


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen;




in Q5, E


8


and E


9


are independently hydrogen, C


1


-C


6


alkyl optionally substituted with halogen, or C


3


-C


6


cycloalkyl optionally substituted with halogen; or E


8


and E


9


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen;




in Q6, E


10


is hydrogen, C


1


-C


6


alkyl optionally substituted with halogen, or C


1


-C


3


alkoxy optionally substituted with halogen; E


11


is hydrogen or C


1


-C


6


alkyl optionally substituted with halogen; or E


10


and E


11


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen; and E


44


is halogen or C


1


-C


3


alkyl;




in Q7, E


12


is C


1


-C


6


alkyl optionally substituted with halogen; and D


4


is oxygen or sulfur;




in Q8, E


13


is C


1


-C


6


alkyl optionally substituted with halogen; and E


14


is hydrogen or halogen;




in Q9, E


15


is hydrogen or C


1


-C


6


alkyl; E


16


is C


1


-C


6


alkyl optionally substituted with halogen; or E


15


and E


16


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen;




in Q10, E


17


, E


18


, and E


19


are independently hydrogen or C


1


-C


6


alkyl; and D


5


is oxygen or sulfur;




in Q11, E


20


and E


21


are independently hydrogen or C


1


-C


6


alkyl; and D


6


is oxygen or sulfur;




in Q12, E


22


and E


23


are independently hydrogen or C


1


-C


6


alkyl;




in Q13, E


24


is hydrogen or C


1


-C


3


alkyl;




in Q14, E


25


is hydrogen, C


1


-C


3


alkyl, or halogen; E


26


is C


1


-C


3


alkyl optionally substituted with halogen; E


27


is hydrogen, amino, C


1


-


6


alkyl, C


3


-C


6


alkenyl, C


3


-C


6


alkynyl, or optionally substituted benzyl; and D


7


is oxygen or sulfur;




in Q15, E


28


is C


1


-C


3


alkyl optionally substituted with halogen; E


29


is hydrogen, amino, C


1


-C


6


alkyl, C


1


-C


6


alkenyl, C


3


-C


6


alkynyl, or optionally substituted benzyl; and D


8


is oxygen or sulfur;




in Q16, E


30


is C


1


-C


3


alkyl optionally substituted with halogen, E


31


is hydrogen or C


1


-C


3


alkyl optionally substituted with halogen; or E


30


and E


31


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen; and E


42


is hydrogen or C


1


-C


3


alkyl optionally substituted with halogen;




in Q17, E


32


is C


1


-C


3


alkyl optionally substituted with halogen; E


33


is hydrogen, halogen, amino, C


1


-C


3


alkyl optionally substituted with halogen, C


1


-C


3


alkoxy optionally substituted with halogen, or C


1


-C


3


alkylthio optionally substituted with halogen; and E


43


is hydrogen or C


1


-C


3


alkyl optionally substituted with halogen;




in Q18, E


34


is C


1


-C


3


alkyl optionally substituted with halogen;




in Q19, D


9


is oxygen or sulfur; and V


1


is —CH


2


—, —CH


2


—CH


2


—, or —CH


2


—CH


2


—CH


2


—;




in Q20, E


35


is C


1


-C


3


alkyl optionally substituted with halogen; Z


2


is nitrogen or CH; and V


2


is —CH


2


—CH


2


—, —CH═CH—, —N═CH—, —CH═N—, or —N═N—;




in Q21, E


36


and E


37


are independently C


1


-C


6


alkyl; or E


36


and E


37


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; D


10


and D


11


are independently oxygen or sulfur; and Z


3


is nitrogen or CH;




in Q22, E


38


is hydrogen or C


1


-C


6


alkyl; E


39


is C


1


-C


3


alkyl optionally substituted with halogen; or E


38


and E


39


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; and D


12


is oxygen or sulfur; and




in Q23, E


40


is hydrogen or C


1


-C


6


alkyl; E


41


is C


1


-C


3


alkyl, or C


3


-C


6


cycloalkyl; or E


40


and E


41


may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO


2


, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; and D


13


is oxygen or sulfur.




The present invention further provides herbicides containing them as active ingredients, and condensed heterocyclic compounds of general formula II:











wherein A


1


is C—R


31


and Y


11


is oxygen, sulfur, or N—R


32


; wherein R


31


is nitro, amino, cyano, carboxyl, or (C


1


-C


3


alkoxy)carbonyl, and R


32


is hydrogen, C


1


-C


5


alkyl, C


3


-C


6


alkenyl, or C


3


-C


6


alkynyl; and Q, R


1


, R


2


, R


3


, and R


4


are as defined above, which heterocyclic compounds are useful as intermediates for the production of the present compounds.




Mode for Carrying Out the Invention




For the groups represented by R


142


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




For the groups-represented by R


143


, C


1


-C


3


alkyl may include methyl, ethyl, propyl, and isopropyl; C


1


-C


3


haloalkyl may include trifluoromethyl and difluoromethyl; and C


1


-C


5


alkoxy may include methoxy, ethoxy, propoxy, and isopropoxy.




For the groups represented by R


145


or R


146


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C


1


-C


5


alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C


1


-C


5


haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C


1


-C


5


alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.




For the groups represented by R


147


or R


148


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.




For the elements or groups represented by R


152


, halogen may include fluorine, chlorine, bromine, and iodine; and C


1


-C


3


alkyl may include methyl, ethyl, propyl, and isopropyl.




For the groups represented by R


153


, C


1


-C


3


alkyl may include methyl, ethyl, propyl, and isopropyl; C


1


-C


3


haloalkyl may include trifluoromethyl and difluoromethyl; and C


1


-C


5


alkoxy may include methoxy, ethoxy, propoxy, and isopropoxy.




For the groups represented by R


156


or R


157


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C


1


-C


5


alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C


1


-C


5


haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C


1


-C


5


alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.




For the groups represented by R


154


or R


155


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C


1


-C


5


alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C


1


-C


5


haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C


1


-C


5


alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.




For the groups or elements represented by R


141


, C


1


-C


3


alkyl may include methyl, ethyl, and isopropyl; and halogen may include fluorine, chlorine, bromine, and iodine.




For groups represented by R


31


, (C


1


-C


3


alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, and isopropoxycarbonyl.




For the groups represented by R


32


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




For the elements or groups represented by R


1


, halogen may include fluorine, chlorine, bromine, and iodine; C


1


-C


3


alkyl may include methyl and ethyl; and C


1


-C


3


haloalkyl may include trifluoromethyl and difluoromethyl.




For the elements or groups represented by R


2


or R


3


, halogen may include fluorine, chlorine, bromine, and iodine; C


1


-C


11


alkyl may include methyl, ethyl, and isopropyl; and C


1


-C


11


haloalkyl may include trichloromethyl, trifluoromethyl, chlorodifluoromethyl, difluoromethyl, pentafluoroethyl, and 1,1-difluoroethyl.




For the elements or groups represented by R


4


, halogen may include fluorine, chlorine, bromine, and iodine; C


1


-C


3


alkyl may include methyl and ethyl; and C


1


-C


3


haloalkyl may include trifluoromethyl and difluoromethyl.




For the groups represented by R


9


or R


59


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl (wherein “t” means “tertiary”; this also holds below), and isoamyl; (C


1


-C


5


alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; and (C


1


-C


5


alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, and t-butoxycarbonyl.




For the groups represented by R


10


, R


11


, R


12


, R


60


, R


61


, or R


62


, C


1


-C


10


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C


1


-C


10


haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C


3


-C


10


cycloalkyl may include cyclopentyl and cyclohexyl; C


1


-C


10


halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C


3


-C


10


cycloalkyl C


1


-C


3


alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C


3


-C


10


alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C


3


-C


10


haloalkenyl may include 2-chloro-2-propenyl and 3,3-dichloro-2-propenyl; C


3


-C


10


alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C


3


-C


10


haloalkynyl may include 3-iodo-2-propynyl and 3-bromo-2-propynyl; cyano C


1


-C


6


alkyl may include cyanomethyl and cyanoethyl; (C


1


-C


5


alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C


1


-C


5


haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; (C


3


-C


10


cycloalkyl)carbonyl may include cyclopropylcarbonyl and cyclopentylcarbonyl; (C


1


-C


5


alkyl)carbonyl C


1


-C


5


alkyl may include 2-oxopropyl, 3-methyl-2-oxobutyl, and 3-oxopentyl; (C


1


-C


5


haloalkyl)carbonyl C


1


-C


5


alkyl may include 3,3,3-trifluoro-2-oxopropyl; hydroxy C


1


-C


5


alkyl may include 2-hydroxyethyl and 4-hydroxybutyl; C


1


-C


5


alkoxy C


1


-C


5


alkyl may include methoxymethyl, 1-methoxyethyl, and ethoxymethyl; C


1


-C


5


alkylthio C


1


-C


5


alkyl may include methylthiomethyl and methylthioethyl; (C


1


-C


5


alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, and t-butoxycarbonyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl may include 4-fluorocyclohexyloxycarbonylmethyl; (C


3


-C


10


alkenoxy)carbonyl C


1


-C


5


alkyl may include allyoxycarbonylmethyl, 1-methyl-2-propenyloxycarbonylmethyl, 1-allyloxycarbonylethyl, and 1-(1-methyl-2-propenyloxy)carbonylethyl; (C


3


-C


10


alkynoxy)carbonyl C


1


-C


5


alkyl may include propargyloxycarbonylmethyl, 1-methyl-2-propynyloxycarbonylmethyl, 1-propargyloxycarbonylethyl, 1-(1-methyl-2-propynyloxy)carbonylethyl; carboxy(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl may include carboxymethoxycarbonylmethyl, 1-carboxyethoxycarbonylmethyl, 1-carboxy-1-methylethoxycarbonylmethyl, 1-(carboxymethoxycarbonyl)ethyl, 1-(1-carboxyethoxycarbonyl)ethyl, and 1-(1-carboxy-1-methylethoxy-carbonyl)ethyl; (C


1


-C


10


alkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethoxycarbonylmethyl, 1-methoxycarbonylethoxycarbonylmethyl, 1-methoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(methoxycarbonylmethoxycarbonyl)ethyl, 1-(1-methoxycarbonylethoxycarbonyl)ethyl, 1-(1-methoxycarbonyl-1-methylethoxycarbonyl)ethyl, ethoxycarbonylmethoxycarbonylmethyl, 1-ethoxycarbonylethoxycarbonylmethyl, 1-ethoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(ethoxycarbonylmethoxycarbonyl)ethyl, 1-(1-ethoxycarbonylethoxycarbonyl)ethyl, 1-(1-ethoxycarbonyl-1-methylethoxycarbonyl)ethyl, isopropoxycarbonylmethoxy-carbonylmethyl, 1-isopropoxycarbonylethoxycarbonylmethyl, 1-isopropoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(isopropoxycarbonylmethoxycarbonyl)ethyl, 1-(1-isopropoxycarbonylethoxycarbonyl)ethyl, and 1-(1-isopropoxycarbonyl-1-methylethoxycarbonyl)ethyl; (C


1


-C


10


haloalkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethoxycarbonylmethyl, 1-(2-chloroethoxycarbonyl)ethoxycarbonylmethyl, 1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonylmethyl, 1-(2-chloroethoxycarbonylmethoxycarbonyl)ethyl, 1-{1-(2-chloroethoxycarbonyl)ethoxycarbonyl}ethyl, and 1-{1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonyl}-ethyl; (C


3


-C


10


cycloalkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethoxycarbonylmethyl, 1-cyclopentyloxycarbonylethoxycarbonylmethyl, 1-cyclopentyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(cyclopentyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-cyclopentyloxycarbonylethoxycarbonyl)ethyl, 1-(1-cyclopentyloxycarbonyl-1-methylethoxycarbonyl)ethyl, cyclohexyloxycarbonylmethoxycarbonylmethyl, 1-cyclohexyloxycarbonylethoxycarbonylmethyl, 1-cyclohexyloxycarbonyl-1-ethylethoxycarbonylmethyl, 1-(cyclohexyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-cyclohexyloxycarbonylethoxycarbonyl)ethyl, and 1-(1-cyclohexyloxycarbonyl-1-methylethoxycarbonyl)ethyl; (C


3


-C


10


alkenoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl may include allyloxycarbonylmethoxycarbonylmethyl, 1-allyloxycarbonylethoxycarbonylmethyl, 1-allyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(allyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-allyloxycarbonylethoxycarbonyl)ethyl, and 1-(1-allyloxycarbonyl-1-methylethoxycarbonyl)ethyl; (C


3


-C


10


alkynoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl C


1


-C


5


alkyl may include propargyloxycarbonylmethoxycarbonylmethyl, 1-propargyloxycarbonylethoxycarbonylmethyl, 1-propargyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(propargyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-propargyloxycarbonylethoxycarbonyl)ethyl, and 1-(1-propargyloxycarbonyl-1-methylethoxycarbonyl)ethyl; carboxy(C


1


-C


5


alkyl)carbonyl may include carboxymethylcarbonyl, carboxyethylcarbonyl, 1-carboxy-1-methylethylcarbonyl, 2-carboxyethylcarbonyl, 3-carboxypropylcarbonyl, and 3-carboxy-1-methylpropylcarbonyl; (C


1


-C


10


alkoxy)carbonyl(C


1


-C


5


alkyl)carbonyl may include methoxycarbonylmethylcarbonyl, 1-methoxycarbonylethylcarbonyl, 1-methoxycarbonyl-1-methylethylcarbonyl, 2-methoxycarbonylethylcarbonyl, 3-methoxycarbonylpropylcarbonyl, 3-methoxycarbonyl-1-methylpropylcarbonyl, ethoxycarbonylmethylcarbonyl, 1-ethoxycarbonylethylcarbonyl, 1-ethoxycarbonyl-1-methylethylcarbonyl, 2-ethoxycarbonylethylcarbonyl, 3-ethoxycarbonylpropylcarbonyl, and 3-ethoxycarbonyl-1-methylpropylcarbonyl; (C


1


-C


10


haloalkoxy)carbonyl(C


1


-C


5


alkyl)carbonyl may include 2-chloroethoxycarbonylmethylcarbonyl, 2,2,2-trifluoroethoxycarbonylmethylcarbonyl, 3-bromopropoxycarbonylmethylcarbonyl, 1-(2-chloroethoxy)carbonylethylcarbonyl, and 1-(2,2,2-trifluoroethoxy)carbonylethylcarbonyl; C


1


-C


5


alkylsulfonyl may include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, and butylsulfonyl; C


1


-C


5


haloalkylsulfonyl may include chloromethylsulfonyl, and trifluoromethylsulfonyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.




For the groups represented by R


13


or R


63


, C


1


-C


10


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, and isoamyl; C


1


-C


10


haloalkyl may include trifluoromethyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, carboxyethyl, 1-carboxyethyl, and 2-carboxypropyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxyvcarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl may include 4-fluorocyclo hexyloxycarbonylmethyl.




For the groups represented by R


14


or R


64


, C


1


-C


10


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C


1


-C


10


haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C


3


-C


10


cycloalkyl may include cyclopentyl and cyclohexyl; C


3


-C


10


halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C


3


-C


10


cycloalkyl C


1


-C


3


alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C


3


-C


10


alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C


3


-C


10


haloalkenyl may include 2-chloro-2-propenyl, and 3,3-dichloro-2-propenyl; C


3


-C


10


alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C


3


-C


10


haloalkynyl may include 3-iodo-2-propynyl, and 3-bromo-2-propynyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, 2-carboxyethyl, and 1-carboxy-1-methylethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonyl methyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-methoxycarbonyl-1-methylethyl, 1-ethoxycarbonyl-1-methylethyl, 1-propoxycarbonyl-1-methylethyl, 1-isopropoxycarbonyl-1-methylethyl, 1-butoxycarbonyl-1-methylethyl, 1-isobutoxycarbonyl-1-methylethyl, 1-t-butoxycarbonyl-1-methylethyl, 1-amyloxycarbonyl-1-methylethyl, 1-isoamyloxycarbonyl-1-methylethyl, and 1-t-butoxycarbonyl-1-methylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, 1-(2,2,2-trifluoroethoxy)carbonylethyl, 1-(2-chloroethoxy)carbonyl-1-methylethyl, and 1-(2,2,2-trifluoroethoxy)carbonyl-1-methylethyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, 1-cyclohexyloxycarbonylethyl, 1-cyclopentyloxycarbonyl-1-methylethyl, and 1-cyclohexyloxycarbonyl-1-methylethyl; (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl may include 4-fluorocyclohexyloxycarbonylmethyl, and 1-(4-fluorocyclohexyloxycarbonyl)-1-methylethyl; (C


3


-C


10


alkenoxy)carbonyl C


1


-C


5


alkyl may include allyloxycarbonylmethyl, 1-methyl-2-propenyloxycarbonylmethyl, 1-allyloxycarbonylethyl, 1-(1-methyl-2-propenyloxy)carbonylethyl, 1-allyloxycarbonyl-1-methylethyl, and 1-(1-methyl-2-propenyloxy)carbonyl-1-methylethyl; (C


3


-C


10


alkynoxy)carbonyl C


1


-C


5


alkyl may include propargyloxycarbonylmethyl, 1-methyl-2-propynyloxycarbonylmethyl, 1-propargyloxycarbonylethyl, 1-(1-methyl-2-propynyloxy)carbonylethyl, 1-propargyloxycarbonyl-1-methylethyl, and 1-(1-methyl-2-propynyloxy)carbonyl-1-methylethyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.




For the groups represented by R


15


or R


65


, C


1


-C


10


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C


1


-C


10


haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C


3


-C


10


cycloalkyl may include cyclopentyl, and cyclohexyl; C


3


-C


10


cycloalkyl C


1


-C


3


alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C


3


-C


10


alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C


3


-C


10


alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; cyano C


1


-C


6


alkyl may include cyanomethyl, and cyanoethyl; carboxyC


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.




For the groups represented by R


16


or R


66


, C


1


-C


10


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; and C


1


-C


10


haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl.




The 3- to 7-membered saturated ring, which is formed by combining R


15


and R


16


or R


65


and R


66


at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.




For the groups represented by R


17


, R


26


, R


27


, R


67


, R


76


, or R


77


, C


1


-C


10


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C


1


-C


10


haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifuoroethyl; C


3


-C


10


cycloalkyl may include cyclopentyl, and cyclohexyl; C


3


-C


10


cycloalkyl C


1


-C


3


alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; (C


1


-C


6


alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, and isopro-poxycarbonyl; and (C


1


-C


6


alkoxy)carbonylmethyl may include methoxy carbonylmethyl, ethoxycarbonylmethyl, and isopropoxycarbonylmethyl.




For the groups represented by R


19


or R


69


, C


1


-C


10


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C


1


-C


10


haloalkyl may include 2-fluoroethyl, 2-chloro-ethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C


3


-C


10


cycloalkyl may include cyclopentyl and cyclohexyl; C


3


-C


10


halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C


3


-C


10


cycloalkyl C


1


-C


3


alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C


3


-C


10


alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C


3


-C


10


haloalkenyl may include 2-chloro-2-propenyl, and 3,3-dichloro-2-propenyl; C


3


-C


10


alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C


3


-C


10


haloalkynyl may include 3-iodo-2-propynyl, and 3-bromo-2-propynyl; cyano C


1


-C


6


alkyl may include cyanomethyl and cyanoethyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.




For the elements or groups represented by R


21


or R


71


, halogen may include fluorine, chlorine, bromine, and iodine; C


1


-C


3


alkyl may include methyl and ethyl; and C


1


-C


3


haloalkyl may include trifluoromethyl.




For the groups represented by R


22


, R


25


, R


72


, or R


75


, (C


1


-C


10


alkoxy) carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, t-butoxycarbonyl, amyloxycarbonyl, and isoamyloxycarbonyl; (C


1


-C


10


haloalkoxy)carbonyl may include 2-chloroethoxycarbonyl, 2-fluoroethoxycarbonyl, 3-bromopropoxycarbonyl, 3-chlorobutoxycarbonyl, and 5,5-dichloroamyloxycarbonyl; (C


3


-C


10


cycloalkoxy)carbonyl may include cyclopentyloxycarbonyl and cyclohexylcarbonyl; (C


3


-C


10


halocycloalkoxy)carbonyl may include 4,4-difluorocyclohexyloxycarbonyl; carboxy(C


1


-C


5


alkoxy)carbonyl may include carboxymethoxycarbonyl, 1-carboxyethoxycarbonyl, and 1-carboxy-1-methylethoxycarbonyl; (C


1


-C


10


alkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl may include methoxycarbonylmethoxycarbonyl, 1-methoxycarbonylethoxycarbonyl, 1-methoxycarbonyl-1-methylethoxycarbonyl, ethoxycarbonylmethoxycarbonyl, 1-ethoxycarbonylethoxycarbonyl, 1-ethoxycarbonyl-1-methylethoxycarbonyl, isopropoxycarbonylmethoxycarbonyl, 1-isopropoxycarbonylethoxycarbonyl, and 1-isopropoxycarbonyl-1-methylethoxycarbonyl; (C


1


-C


10


haloalkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl may include 2-chloroethoxycarbonylmethoxycarbonyl, 1-(2-chloroethoxycarbonyl)ethoxycarbonyl, and 1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonyl; (C


3


-C


10


cycloalkoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl may include cyclopentyloxycarbonylmethoxycarbonyl, 1-cyclopentyloxycarbonylethoxycarbonyl, 1-cyclopentyloxycarbonyl-1-methylethoxycarbonyl, cyclohexyloxycarbonylmethoxycarbonyl, 1-cyclohexyloxycarbonylethoxycarbonyl, and 1-cyclohexyloxycarbonyl-1-methylethoxycarbonyl; (C


3


-C


10


alkenoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl may include allyloxycarbonylmethoxycarbonyl, 1-allyloxycarbonylethoxycarbonyl, and 1-allyloxycarbonyl-1-methylethoxycarbonyl; and (C


3


-C


10


alkynoxy)carbonyl(C


1


-C


5


alkoxy)carbonyl may include propargyloxycarbonylmethoxycarbonyl, 1-propargyloxycarbonylethoxycarbonyl, and 1-propargyloxycarbonyl-1-methylethoxycarbonyl




For the elements or groups represented by R


23


, R


24


, R


73


, or R


74


, halogen may include fluorine, chlorine, bromine, and iodine; C


1


-C


3


alkyl may include methyl, and ethyl; and C


1


-C


3


haloalkyl may include trifluoromethyl.




For the elements or groups represented by R


43


, R


44


, R


163


, or R


164


, halogen may include fluorine, chlorine, bromine, and iodine; C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; and C


1


-C


5


haloalkyl may include trifluoromethyl.




For the groups represented by R


45


, R


46


, R


165


, or R


166


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




The 3- to 7-membered saturated ring, which is formed by combining R


45


, and R


46


or R


165


and R


166


at their ends, together with the adjacent nitrogen atom, may include aziridine ring, azetidine ring, pyrrolidine ring, and piperidine ring.




For the elements and groups represented by R


47


, R


48


, R


167


, or R


168


, halogen may include fluorine, chlorine, bromine, and iodine; C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; and C


1


-C


5


haloalkyl may include trifluoromethyl.




For the groups represented by R


49


, R


50


, R


169


, or R


170


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl, and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




The 3- to 7-membered ring, which is formed by combining R


49


and R


50


or R


169


and R


170


at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.




For the groups represented by R


51


, R


52


, R


171


, or R


172


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




The 3- to 7-membered ring, which is formed by combining R


51


and R


52


or R


171


and R


172


at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.




For the groups represented by R


53


, R


54


, R


173


, or R


174


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




The 3- to 7-membered ring, which is formed by combining R


53


and R


54


or R


173


and R


174


at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.




For the groups represented by R


55


, R


57


, R


175


, or R


177


, C


1


-C


3


alkyl may include methyl, ethyl, and propyl.




For the groups represented by R


55


, R


57


, R


175


, or R


177


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; (C


1


-C


5


alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and propyloxycarbonyl; (C


1


-C


5


haloalkoxy)carbonyl may include trifluoromethoxycarbonyl and 2,2,2-trifluoroethoxycarbonyl; (C


3


-C


5


cycloalkoxy)carbonyl may include cyclopropyloxycarbonyl; (C


3


-C


5


alkenoxy)carbonyl may include allyloxycarbonyl; and (C


3


-C


5


alkynoxy)carbonyl may include propargyloxycarbonyl.




For the groups represented by R


79


or R


179


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C


3


-C


10


halocycloalkoxy) carbonyl C


1


-C


5


alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.




For the groups represented by R


80


or R


180


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




The 3- to 7-membered ring, which is formed by combining R


79


and R


80


or R


179


and R


180


at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.




For the groups represented by R


81


or R


181


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1(2,2,2-trifluoroethoxy)carbonylethyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.




For the groups represented by R


82


or R


182


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.




For the groups represented by R


83


or R


183


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include; allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1methylpropynyl.




The 3- to 7-membered ring, which is formed by combining R


82


and R


83


or R


182


and R


183


at their ends, together with the adjacent nitrogen, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.




For the groups represented by R


84


or R


184


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.




For the groups represented by R


85


or R


185


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




The 3- to 7-membered ring, which is formed by combining R


84


and R


85


or R


184


and R


185


at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.




For the groups represented by R


86


or R


186


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl; carboxy C


1


-C


5


alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C


1


-C


10


alkoxy)carbonyl C


1


-C


5


alkyl may include methoxycarbonylmethyl. ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C


1


-C


10


haloalkoxy)carbonyl C


1


-C


5


alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C


3


-C


10


cycloalkoxy)carbonyl C


1


-C


5


alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C


3


-C


10


halocycloalkoxy)carbonyl C


1


-C


5


alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.




For the groups represented by R


87


or R


187


, C


1


-C


5


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C


1


-C


5


haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C


3


-C


8


cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C


3


-C


6


alkenyl may include allyl and 1-methylpropenyl; and C


3


-C


6


alkynyl may include propargyl and 1-methylpropynyl.




The 3- to 7-membered ring, which is formed by combining R


86


and R


87


or R


186


and R


187


at their ends, together with the adjacent nitrogen atom, may include aziridine ring, azetidine ring, pyrrolidine ring, and piperidine ring.




For the groups represented by E


1


or E


2


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl; and C


3


-C


6


cycloalkyl optionally substituted with halogen may include cyclopropyl cyclobutyl, and cyclopentyl.




The 4- to 7-membered unsaturated rig, which is formed by combining E


1


and E


2


at their ends and which contains, together with the atoms attached thereto on Q1, zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


1


and E


2






For the groups represented by E


3


or E


4


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C


3


-C


6


cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.




The 4- or 7-membered saturated or unsaturated ring, which is formed by combining E


3


and E


4


at their ends and which contains, together with the atoms attached thereto on Q2, zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


3


and E


4


.




For the groups represented by E


5


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 3-fluoropropyl, and 4-fluorobutyl.




For the groups or elements represented by E


6


or E


7


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C


3


-C


6


cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.




The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E


6


and E


7


at their ends and which contains, together with the atoms attached thereto on Q4, zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


6


and E


7


.




For the groups represented by E


8


or E


9


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C


3


-C


6


cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.




The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E


8


and E


9


at their ends and which contains, together with the atoms attached thereto on Q5, zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


8


and E


9


.




For the groups represented by E


10


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C


1


-C


3


alkoxy optionally substituted with halogen may include methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, and difluoromethoxy.




For the groups represented by E


11


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, and 3-fluoropropyl.




The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E


10


and E


11


at their ends and which contains, together with the atoms attached thereto on Q6, zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


10


and E


11


.




For the elements or groups represented by E


44


, halogen may include fluorine, chlorine, bromine, or iodine; and C


1


-C


3


alkyl may include methyl, ethyl, propyl, and isopropyl




For the groups represented by E


12


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




For the groups represented by E


13


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




For the elements represented by E


14


, halogen may include chlorine, bromine, and iodine.




For the groups represented by E


15


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, and amyl.




For the groups represented by E


16


, C


1


-C


6


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E


15


and E


16


at their ends and which contains, together with the atoms attached thereto on Q9, zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


15


and E


16


.




For the groups represented by E


17


, E


18


, or E


19


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.




For the groups represented by E


20


or E


21


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.




For the groups represented by E


22


or E


23


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.




For the groups represented by E


24


, C


1


-C


3


alkyl may include methyl, ethyl, propyl, and isopropyl.




For the groups or elements represented by E


25


, C


1


-C


3


alkyl may include methyl, ethyl, propyl, and isopropyl; and halogen may include fluorine, chlorine, bromine, and iodine.




For the groups represented by E


26


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




For the groups represented by E


27


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl; C


3


-C


6


alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C


3


-C


6


alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; and optionally substituted benzyl may include benzyl.




For the groups represented by E


28


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl




For the groups represented by E


29


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl; C


3


-C


6


alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C


3


-C


6


alkynyl may include propargyl, 1-methyl-3-propynyl, 2-butynyl, 3-butynl, and 1,1-dimethyl-2-propynyl; and optionally substituted benzyl may include benzyl.




For the groups represented by E


30


or E


31


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




The 4- to 7-membered unsaturated ring, which is formed by combining E


30


and E


31


at their ends and which contains zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene or trimethylene is formed by E


30


and E


31


.




For the groups represented by E


42


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




For the groups represented by E


32


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




For the elements or groups represented by E


33


, halogen may include chlorine, bromine, and iodine; C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl and pentafluoroethyl; C


1


-C


3


alkoxy optionally substituted with halogen may include methoxy and ethoxy; and C


1


-C


3


alkylthio optionally substituted with halogen may include methylthio and ethylthio.




For the groups represented by E


43


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




For the groups represented by E


34


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




For the groups represented by E


35


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




For the groups represented by E


36


or E


37


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.




The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E


36


and E


37


at their ends and which contains, together with the atoms attached thereto on Q21, zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


36


and E


37


.




For the groups represented by E


38


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.




For the groups represented by E


39


, C


1


-C


3


alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.




The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E


38


and E


39


at their ends and which contains, together with the atoms attached thereto on Q22, zero to two O, S, SO, SO


2


or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


38


and E


39


.




For the groups represented by E


40


, C


1


-C


6


alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.




For the groups represented by E


41


, C


1


-C


3


alkyl may include methyl, ethyl, propyl, and isopropyl; and C


3


-C


6


cycloalkyl may include cyclopropyl, cyclopentyl, and cyclohexyl.




The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E


40


and E


41


at their ends and which contains, together with the atoms attached thereto on Q23 (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E


40


and E


41


.




For the present compounds, there may exist geometrical isomers based on the presence of a double bond, or optical isomers and diastereomers based on the presence of at least one asymmetric carbon atom, and all of these isomers and their mixtures are also included within the scope of the present invention.




The preferred substituents from the viewpoint of herbicidal activity may include CH, CCH


3


, CCl, CBr and N, more preferably CH and N, for A, and Q1, Q2, Q4, Q6, Q14, Q16, Q18, Q19 and Q20 for Q.




When Q is Q1, compounds in which E


1


and E


2


are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered unsaturated ring are preferred, and in particular; compounds in which the unsaturated ring is a 6-membered ring are more preferred.




When Q is Q2, compounds in which E


3


and E


4


are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring and D


1


and D


2


are oxygen are more preferred.




When Q is Q4, compounds in which E


6


is C


1


-C


6


alkyl optionally substituted with halogen and E


7


is C-C


6


alkyl optionally substituted with halogen are preferred, and in particular, compounds in which E


6


is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) and E


7


is methyl or ethyl are more preferred. In addition, compounds in which E


6


and E


7


are combined at their ends to form, together with the atoms attached thereto, a 5- or 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring are more preferred.




When Q is Q6, compounds in which E


10


is C


1


-C


6


alkyl optionally substituted with halogen, E


11


is C


1


-C


6


alkyl optionally substituted with halogen, and E


44


is chlorine or bromine are preferred, and in particular, compounds in which E


10


is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) and E


11


is methyl or ethyl are more preferred. In addition, compounds in which E


10


and E


11


are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring are more preferred.




When Q is Q14, compounds in which D


7


is oxygen, E


25


is hydrogen, E


26


is C


1


-C


3


alkyl optionally with halogen, and E


27


is C


1


-C


3


alkyl are preferred, and in particular, compounds in which E


26


is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) and E


27


is methyl or ethyl are more preferred.




When Q is Q16, compounds in which E


30


is C


1


-C


3


alkyl optionally substituted with halogen, E


31


is hydrogen or C


1


-C


3


alkyl, and E


42


is hydrogen or C


1


-C


3


alkyl are preferred, and in particular, compounds in which E


30


is methyl, methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl), or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl), E


31


is hydrogen or methyl, and E


42


is hydrogen or methyl are more preferred. In addition, compounds in which E


30


and E


31


are combined at their ends to form, together with the atoms attached thereto, a 5- or 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 5- or 6-membered ring are more preferred.




When Q is Q18, compounds in which E


34


is C


1


-C


3


alkyl optionally substituted with halogen are preferred, and in particular, compounds in which E


34


is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) are more preferred.




When Q is Q19, compounds in which V


1


is —CH


2


— or —CH


2


—CH


2


— are preferred.




When Q is Q20, compounds in which E


35


is C


1


-C


3


alkyl optionally substituted with halogen, Z


2


is nitrogen, and V


2


is —CH


2


—CH


2


— or —CH═CH— are preferred, and in particular, compounds in which E


35


is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) are more preferred.




Specific examples of the preferred compounds are recited below:




Methyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;




Ethyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;




Isopropyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetraydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;




Methyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2 3,6-tetrahydropyrimidin-1-yl]-6-nitrobenzo[b]furan-5-carboxylate;




Ethyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-6-nitrobenzo[b]furan-5-carboxylate;




Methyl 6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;




Ethyl 6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;




Methyl 7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;




Ethyl 7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;




3-(5-Methoxybenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-(5-Methoxy-6-nitrobenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-(6-Chloro-5-methoxybenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-(7-Chloro-5-methoxybenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-[5-(Allyloxy)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-[5-(Allyloxy)-6-nitrobenzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-[5-(Allyloxy)-6-chlorobenzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-[5-(Allyloxy)-7-chlorobenzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




1-Methyl-3-[5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-6-(trifluoroethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




1-Methyl-3-[6-nitro-5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-[6-Chloro-5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-[7-Chloro-5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




Ethyl 2-({3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;




Ethyl 2-({6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;




Ethyl 2-({7-chloro-3-[3-methyl-2,6-dioxo-4-(trifuoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;




1-Methyl-3-[5-(methylthio)benzo[b]furan-3-yl]-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




1-Methyl-3-[5-(methylthio)-6-nitrobenzo[b]furan-3-yl]-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-[6-Chloro-5-(methylthio)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-[7-Chloro-5-(methylthio)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




Ethyl 2-({3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-6-nitrobenzo[b]furan-5-yl}thio)propanoate;




Ethyl 2-({6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidim-1-yl]benzo[b]furan-5-yl}thio)propanoate;




Ethyl 2-({7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}thio)propanoate;




3-(5,7-Dichlorobenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;




3-(5-Bromo-7-chlorobenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione; and




3-(7-Chloro-5-methylbenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione.




The present compounds can be produced, for example, by Producing Processes 1 to 27 as described below.




PRODUCING PROCESS 1




In the process, compound a-1 of the general formula:











wherein T, A, Y, R


1


, R


2


, R


3


, and R


4


are as defined above, is reacted with acid anhydride a-5 of the general formula:











wherein E


1


and E


2


are as defined above.




The reaction is carried out without solvent or in a solvent. The reaction temperature is usually in the range of 50° C. to 200° C. The reaction time is usually in the range of 1 to 100 hours. The amounts of reagents to be used in the reaction are 1 mole of acid anhydride a-5 relative to 1 mole of compound a-1, which is the stoichiometric ratio but can be freely changed depending upon the reaction conditions.




The solvent which can be used may include aliphatic hydrocarbons such as hexane, heptane, octane, and ligroin; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, and mesitylene; halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, and trichlorobenzene; ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl t-butyl ether; nitro compounds such as nitromethane and nitrobenzene; organic acids such as acetic acid and propionic acid; acid amides such as N,N-dimethylformamide; sulfur compounds such as dimethylsulfoxide and sulforane; and mixtures thereof. In addition, acids such as p-toluenesulfonic acid can also be used as a reaction catalyst.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography. (see JP-A 55-139359.)




PRODUCING PROCESS 2




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, D


1


, D


2


, E


3


, E


4


, T, A, and Y are as defined above, R


200


is C


1


-C


5


alkyl (e.g., methyl, ethyl) or hydrogen.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-27985, or for example, by the following processes.




1). Process of Producing Compound a-2 from Compound a-1




Compound a-2 can be produced by converting compound a-1 into an isocyanate or isothiocyanate derivative in a solvent or without solvent.




Agent for conversion into isocyanate or isothiocyanate derivatives: phosgene, trichloromethyl chloroformate, oxalyl chloride, thiophosgene, etc.




Amount of agent for conversion into isocyanate or isothiocyanate derivatives: 1 equivalent to an excess amount relative to 1 mole of compound a-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.




Reaction temperature: room temperature to the reflux temperature of the agent for conversion into isocyanate or isothiocyanate derivatives




Reaction time: a moment to 48 hours.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound a-3 from Compound a-2




Compound a-3 can be produced by reacting compound a-2 with compound a-6 of the general formula:











wherein D


1


, E


3


, E


4


, and R


200


are as defined above, in a solvent in the presence of a base.




Amount of compound a-6: 1 to 5 moles relative to 1 mole of compound a-2




Kind of base: inorganic bases such as sodium hydride and potassium carbonate; organic bases such as triethylamine; metal alcoholates such as sodium methylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-2




Solvents: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol; and mixtures thereof; etc.




Reaction temperature: −15° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound a-4 may be directly obtained depending upon the reaction conditions of this process.




3) Process of Producing Compound a-4 from Compound a-3




Compound a-4 can be produced by reacting compound a-3 in a solvent in the presence of a base.




Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate; etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound a-3




Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as methanol and ethanol; and mixtures thereof; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 3




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, R


200


, D


1


, D


2


, E


3


, E


4


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-27985, or for example, by the following processes.




1) Process of Producing Compound b-3 from Compound a-2




Compound b-3 can be produced by reacting compound a-2 with compound b-5 of the general formula:











wherein D


1


, E


3


, E


4


, and R


200


are as defined above, in a solvent in the presence of a base.




Amount of compound b-5: 1 to 5 moles relative to 1 mole of compound a-2




Kind of base: inorganic bases such as sodium hydride and potassium carbonate; organic bases such as triethylamine; metal alcoholates such as sodium methylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-2




Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol; and mixtures thereof; etc.




Reaction temperature: −15° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound b-4 may be directly obtained depending upon the reaction conditions of this process.




2) Process of Producing Compound b-4 from Compound b-3




Compound b-4 can be produced by reacting compound b-3 in a solvent in the presence of a base.




Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate; etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound b-3




Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as methanol and ethanol; and mixtures thereof; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 4




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, D


3


, E


5


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in WO87/03873, or for example, by the following processes.




1) Process of Producing Compound c-1 from Compound a-1




Compound c-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).




2) Process of Producing Compound c-2 from Compound c-1




Compound c-2 can be produced by reacting compound c-1 and trimethylsilyl azide in a solvent or without solvent.




Amount of trimethylsilyl azide: 1 to 3 moles relative to 1 mole of compound c-1




Solvent: benzene, toluene, chlorobenzene, etc.




Reaction temperature: room temperature to the reflux temperature




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound c-3 from Compound c-2




Compound c-3 can be produced by reacting compound c-2 and compound c-4 of the general formula:






M


1


—E


5


  c-4






wherein E


5


is as defined above and M


1


is chlorine, bromine, iodine, or methanesulfonyloxy, in a solvent in the presence of a base.




Amount of compound c-4: 1 to 3 moles relative to 1 mole of compound c-2




Kind of base: sodium hydride, potassium carbonate, etc.




Amount of base: 1 to 10 moles relative to 1 mole of compound c-2




Solvent: N,N-dimethylformamide, tetrahydrofuran, etc.




Reaction temperature: room temperature to 150° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 5




This is the producing process according to the following scheme:











wherein R


201


is methoxy, ethoxy or dimethylamino; and R


1


, R


2


, R


3


, R


4


, E


6


, E


7


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-149571, or for example, by the following processes.




1) Process of Producing Compound d-1 from Compound a-1




Compound d-1 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with a reducing agent such as tin (II) chloride. (see Organic Synthesis Collective Volume 1, p. 442.)




(Diazonium Salt Formation)




Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1




Kind of acid: hydrochloric acid etc.




Amount of acid: 1 mole to an excess amount relative to 1 mole of compound a-1




Solvent: water, ethanol, hydrochloric acid, etc.




Reaction temperature: −15° C. to room temperature




Reaction time: a moment to 24 hours




(Reduction Reaction)




Kind of reducing agent: tin (II) chloride etc.




Amount of reducing agent: 3 to 10 moles relative to 1 mole of compound a-1




Solvent: hydrochloric acid etc.




Reaction temperature: −15° C. to room temperature




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound d-3 from Compound d-1




Compound d-3 can be produced by reacting compound d-1 and compound d-5 of the general formula:











wherein E


7


and R


201


are as defined above and R


202


is methyl or ethyl, in a solvent, if necessary, in the presence of a base, to give intermediate d-2 and then reacting the intermediate d-2 in the presence of a base.




Intermediate d-2 may be isolated.




(Reaction of Compound d-1 into Compound d-2)




Amount of compound d-5: 1 to 3 moles relative to 1 mole of compound d-1.




Kind of base: organic bases such as triethylamine and pyridine; metal alcoholates such as sodium methylate and sodium ethylate; inorganic bases such as sodium hydroxide and potassium carbonate; etc.




Solvent: aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol and isopropanol; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




(Reaction of Compound d-2 into Compound d-3)




Kind of base: organic bases such as triethylamine and pyridine; metal alcoholates such as sodium methylate and sodium ethylate; inorganic bases such as sodium hydroxide and potassium carbonate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-1




Solvent: aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol and isopropanol; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound d-4 from Compound d-3




Compound d-4 can be produced by reacting compound d-3 with compound d-6 of the general formula:






M


1


—E


6


  d-6






wherein E


6


and M


1


are as defined above, in a solvent in the presence of a base.




Amount of compound d-6: 1 to 3 moles relative to 1 mole of compound d-3




Kind of base: sodium hydride, potassium carbonate, etc.




Amount of base: 1 to 10 moles relative to 1 mole of compound d-3




Solvent: N,N-dimethylformamide, tetrahydrofuran, etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound d-3 can also be produced according to the following scheme. (see JP-A 7-503253.)











wherein R


1


, R


2


, R


3


, R


4


, E


7


, T, A, and Y are as defined above.




1) Process of Producing Compound e-1 from Compound d-1




Compound e-1 can be produced by reacting compound d-1 with compound e-3 of the general formula:











wherein E


7


is as defined above, in a solvent.




Amount of compound e-3: 1 to 10 moles relative to 1 mole of compound d-3




Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.




Reaction temperature: −15° C. to 70° C.




Reaction time: a moment to 24 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound e-1 can also be used as such for the reaction in the next step without isolation.




2) Process of Producing Compound e-2 from Compound e-1




Compound e-2 can be produced by reacting compound e-1 with an alkali metal cyanate, in a solvent, if necessary, in the presence of an acid.




Kind of alkali metal cyanate: NaOCN, KOCN, etc.




Amount of alkali metal cyanate: 1 to 3 moles relative to 1 mole of compound e-1




Kind of acid: organic acids such as acetic acid




Amount of acid: 0.01 to 1 mole relative to 1 mole of compound e-1




Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.




Reaction temperature: −15° C. to 80° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallzation or column chromatography.




Compound e-2 can also be used as such in the next step without isolation.




3) Process of Producing Compound d-3 from Compound e-2




Compound d-3 can be produced by oxidizing compound e-2 with an oxidizing agent such as halogen, hypohalous acid, or hypohalite in a solvent.




Kind of oxidizing agent: chlorine, hypochlorous acid, sodium hypochlorite, etc.




Amount of oxidizing agent: 1 to 3 moles relative to 1 mole of compound e-2




Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.




Reaction temperature: −15° C. to 60° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example; the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 6




This is the producing process according to the following scheme:











wherein R


1


, R


1


, R


3


, R


4


, E


10


, E


11


, T, A, and Y are as defined above; E


144


is halogen; and R


203


is methyl or ethyl.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-233061, or for example, by the following processes.




1) Process of Producing Compound f-2 from Compound d-1




Compound f-2 can be produced by reacting compound d-1 with compound f-4 of the general formula:











wherein E


10


, E


11


, and R


203


are as defined above, in a solvent, if necessary, in the presence of an acid.




Amount of compound f-4: 1 to 10 moles relative to 1 mole of compound d-1




Solvent: water; alcohols such as ethanol, isopropanol and butanol; aromatic hydrocarbons such as benzene and toluene; organic acids such as acetic acid and propionic acid; and mixtures thereof; etc.




Kind of acid: p-toluenesulfonic acid, hydrochloric acid, acetic acid, etc.




Amount of acid: 0.0001 mole to an excess amount relative to 1 mole of compound d-1




Reaction temperature: room temperature to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound f-3 from Compound f-2




Compound f-3 can be produced by reacting compound f-2 with a halogenating agent in a solvent or without solvent under normal pressure or increased pressure.




Kind of halogenating agent: phosphorous oxychloride, phosphorous pentachloride, oxalyl chloride, phosgene, trichloromethyl chloroformate, etc.




Amount of halogenating agent: 1 mole to an excess amount relative to 1 mole of compound f-2




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.




Reaction temperature: 50° C. to 250° C.




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




The compounds wherein E


10


is CF


2


H can also be produced according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


11


, E


144


, T, A, and Y are defined above.




1) Process of Producing Compound g-2 from Compound g-1




Compound g-2 can be produced by reacting compound g-1 with a Vilsmeier reagent (prepared from dimethylformamide and a halide such as phosphorus oxychloride, phosphorus pentachloride, oxalyl chloride, phosgene or trichloromethyl chloroformate; see Jikken Kagaku Koza, 4th Edition, 21, p. 110) in a solvent or without solvent.




Amount of Vilsmeier reagent: 1 to 20 moles relative to 1 mole of compound g-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: −10° C. to 150° C.




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaing the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound g-3 from Compound g-2




Compound g-3 can be produced by reacting compound g-2 with a fluorinating agent in a solvent.




Kind of fluorinating agent: dimethylaminosulfur trifluoride etc.




Amount of fluorinating agent: 1 to 10 moles relative to 1 mole of compound g-2




Solvent: halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: −10° C. to room temperature




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 7




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


12


, D


4


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-109578, or for example, by the following processes.




1) Process of Producing Compound h-1 from Compound d-1




Compound h-1 can be produced by reacting compound d-1 with an acylating agent selected from compound h-3 of the general formula:











wherein E


12


is as defined above and R


204


is hydrogen, methyl, or ethyl, compound h-4 of the general formula:











wherein E


12


is as defined above, and compound h-5 of the general formula:











wherein E


12


is as defined above, in a solvent or without solvent.




Amount of acylating agent: 1 to 5 moles relative to 1 mole of compound d-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound h-2 from Compound h-1




Compound h-2 can be produced by reacting compound h-1 with compound h-6 of the general formula:











wherein D


4


is as defined above, in a solvent in the presence of a base.




Amount of compound h-6: 1 to 5 moles of compound h-1




Kind of base: organic bases such as ti4triethylamine and pyridine; inorganic bases such as potassium carbonate; etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound h-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: −10° C. to room temperature




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 8




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


13


, T, A, and Y are as defined above; E


114


is halogen; and R


205


is methyl or ethyl.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-145011, or for example, by the following processes.




1) Process of Producing Compound i-1 from Compound a-1




Compound i-1 can be produced by reacting compound a-1 with a chloroformate i-5 of the general formula:






ClCOOR


205


  i-5






wherein R


205


is as defined above, in a solvent in the presence of a base.




Amount of chloroformate i-5: 1 to 10 moles relative to 1 mole of compound a-1




Kind of base: N,N-dimethylaniline, N,N-diethylaniline, etc.




Amount of base: 1 to 10 moles relative to 1 mole of compound a-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: room temperature to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound i-2 from Compound i-1




Compound i-2 can be produced by reacting compound i-1 with compound i-6 of the general formula:











wherein E


13


is as defined above and M


6


is chlorine or bromine, in a solvent in the presence of lithium bis(trimethylsilyl)amide.




Amount of compound i-6: 1 to 10 moles relative to 1 mole of compound i-1




Amount of lithium bis(trimethylsilyl)amide: 1 to 10 moles relative to 1 mole of compound i-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: room temperature to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound i-3 from Compound i-2




Compound i-3 can be produced by reacting compound i-2 with a halogenating agent in a solvent.




Kind of halogenating agent: chlorine, bromine, etc.




Amount of halogenating agent: 1 mole to large excess relative to 1 mole of compound i-2




Solvent: halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: 10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound i-4 from Compound i-3




Compound i-4 can be produced by reacting compound i-3 with a base in a solvent.




Kind of base: organic bases such as triethyl amine and 1,8-diazabicylo[5.4.0]undec-7-ene; etc.




Amount of base: 1 mole to large excess relative to 1 mole of compound i-3




Solvent: dimethylsulfoxide etc.




Reaction temperature: 10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 9




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


15


, E


16


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-104073, or for example, by the following processes.




1) Process of Producing Compound j-1 from Compound d-1




Compound j-1 can be produced by reacting compound d-1 with compound j-3 of the general formula:











wherein E


15


and E


16


are as defined above, in a solvent, if necessary, in the presence of an acid.




Amount of compound j-3: 1 to 5 moles relative to 1 mole of compound d-1




Solvent: toluene, ethanol, acetic acid, tetrahydrofuran, etc.




Acid: p-toluenesulfonic acid etc.




Reaction temperature: −10° C. to 100° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound j-2 from Compound j-1




Compound j-2 can be produced by reacting compound j-1 with an oxidizing agent in a solvent in the presence of a pyridine.




Amount of pyridine: 1 to 2 moles relative to 1 mole of compound j-1




Kind of oxidizing agent: copper (II) sulfate etc.




Amount of oxidizing agent: 1 to 5 moles relative to 1 mole of compound j-1




Solvent: toluene, ethanol, acetic acid, tetrahydrofuran, etc.




Reaction temperature: −10° C. to 100° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 10




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


17


, E


18


, E


19


, D


5


, T, A, and Y are as defined above and R


206


is methyl or ethyl.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-183567, or for example, by the following processes.




1) Process of Producing Compound k-1 from Compound a-1




Compound k-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).




2) Process of Producing Compound k-2 from Compound k-1




Compound k-2 can be produced by reacting compound k-1 with compound k-5 of the general formula:











wherein E


18


, E


19


, and R


206


are as defined above, in a solvent in the presence of a base.




Amount of compound k-5: 1 to 2 moles relative to 1 mole of compound k-1




Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound k-1




Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.




Reaction temperature: −10° C. to 100° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound k-3 may be obtained directly depending upon the reaction conditions of this process.




3) Process of Producing Compound k-3 from Compound k-2




Compound k-3 can be produced by reacting compound k-2 in a solvent in the presence of a base.




Kind of base: potassium carbonate, sodium hydride, sodium methylate, etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound k-2




Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.




Reaction temperature: −10° C. to 100° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound k-4 from Compound k-3




Compound k-4 can be produced by reacting compound k-3 with compound k-6 of the general formula:






M


7


—E


17


  k-6






wherein E


7


is as defined above and M


7


is iodine, bromine, or chlorine, in a solvent in the presence of a base.




Amount of compound k-6: 1 to 2 molesrelative to 1 mole of compound k-3




Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound k-3




Solvent: toluene, ethanol, tetrahydrofuran, N,N-diinethylformamide, etc.




Reaction temperature: −10° C. to 100° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to ost-treatments, for example, the reaction mixture is poured into water, and he deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaiing the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 11




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


20


, E


21


, D


6


, T, A, and Y are as defined above and R


207


is methyl or ethyl.




The reactions in the respective steps can be carried out, for example, according to the processes as described in WO87/62357, or for example, by the following processes.




1) Process of Producing Compound l-1 from Compound a-1




Compound l-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).




2) Process of Producing Compound l-2 from Compound l-1




Compound l-2 can be produced by reacting compound l-1 with compound l-4 of the general formula.











wherein E


20


, E


21


, and R


207


are as defined above, in a solvent in the presence of a base.




Amount of compound l-4: 1 to 2 moles relative to 1 mole of compound l-1




Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound l-1




Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.




Reaction temperature: −10° C. to 100° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound l-3 may be obtained directly depending upon the reaction conditions of this process.




3) Process of Producing Compound l-3 from Compound l-2




Compound l-3 can be produced by reacting compound l-2 in a solvent in the presence of a base.




Kind of base: potassium carbonate, sodium hydride, sodium methylate, etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound l-2




Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.




Reaction temperature: −10° C. to 100° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 12




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


22


, E


23


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-103801, or for example, by the following processes.




1) Process of Producing Compound m-1 from Compound a-1




Compound m-1 can be produced by reacting compound a-1 with acid anhydride m-2 of the general formula:











wherein E


22


and E


23


are as defined above, usually without solvent, or in a solvent, if necessary, in the presence of an acid.




The reaction temperature is usually in the range of 50° C. to 200° C. The reaction time is usually in the range of 1 to 100 hours. The amounts of agents to be used in the reaction are 1 mole of acid anhydride m-2 relative to 1 mole of compound a-1, which; is the stoichiometric ratio but can be freely changed depending upon the reaction conditions.




The solvent which can be used may include aliphatic hydrocarbons such as hexane, heptane, octane, and ligroin; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, and mesitylene; halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, and trichlorobenzene; ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl t-butyl ether; nitro compounds such as nitromethane and nitrobenzene; organic acids such as acetic acid and propionic acid; acid amides such as N,N-dimethylformamide; sulfur compounds such as dimethylsulfoxide and sulforane; and mixtures thereof As the acid, p-toluenesulfonic acid can be used.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 13




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


24


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in WO86/00072, or for example, by the following processes.




1) Process of Producing Compound n-1 from Compound a-1




Compound n-1 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in a solvent in the presence of an acid and then reacting the diazonium salt with compound n-5 of the formula:











in a solvent in the presence of a base.




(Diazonium salt formation)




Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1




Kind of acid: hydrochloric acid etc.




Amount of acid: 1 mole to an excess amount relative to 1 mole of compound a-1




Solvent: water, ethanol, hydrochloric acid, etc.




Reaction temperature: −15° C. to room temperature




Reaction time: a moment to 24 hours




(Reaction with compound n-5)




Amount of compound n-5: 1 to 5 moles relative to 1 mole of compound a-1




Kind of base: sodium acetate etc.




Amount of base: 0.8 to 3 moles relative to 1 mole of acid used in the forgoing step




Solvent: ethanol, water, etc.




Reaction temperature: 0°C. to 60° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound n-2 from Compound n-1




Compound n-2 can be produced by reacting compound n-1 in a solvent in the presence of a base.




Kind of base: sodium hydroxide, potassium hydroxide, etc.




Amount of base: 1 to 10 moles relative to 1 mole of compound n-1




Solvent: ethanol, N,N-dimethylformamide, water, and mixtures thereof; etc.




Reaction temperature: 0° C. to 110° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound n-3 from Compound n-2




Compound n-3 can be produced by reacting compound n-2 in a solvent in the presence of thioacetic acid.




Amount of thioacetic acid: 0.1 to 10 moles relative to 1 mole of compound n-2




Solvent: xylene etc.




Reaction temperature: reflux temperature




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound n-4 from Compound n-3




Compound n-4 can be produced by reacting compound n-3 with compound n-6 of the general formula:






M


8


—E


24


  n-6






wherein E


24


is as defined above and M


8


is iodine, bromine, or chlorine, in a solvent in the presence of a base.




Amount of compound n-6: 1 to 10 moles relative to 1 mole of compound n-3




Kind of base: potassium carbonate, sodium hydride, etc.




Amount of base: 1 to 10 moles relative to 1 mole of compound n-3




Solvent: acetone, tetrahydrofuran, N,N-dimethylformamide, etc.




Reaction temperature: 0° C. to 100° C.




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 14




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


25


, E


26


, E


27


, T, A, and Y are as defined above, and R


208


and R


209


are independently C


1


-C


5


alkyl (e.g., methyl, ethyl, propyl).




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 5-4959 and JP-A 63-41466, or for example, by the following processes.




1) Process of Producing Compound o-1 from Compound a-1




Compound o-1 can be produced from compound a-1 and chloroformate o-4 of the general formula:






ClCOOR


208


  o-4






wherein R


208


is as defined above, according to the process as described above in Producing Process 8, Step 1).




2) Process of Producing Compound o-11from Compound o-1




Compound o-11 can be produced by reacting compound o-1 with compound o-5 of the general formula:











wherein E


25


, E


26


, and R


209


are as defined above, in a solvent in the presence of a base.




Amount of compound o-5: 0.9 to 10 moles relative to 1 mole of compound o-1




Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound o-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.




Reaction temperature: room temperature to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound o-11can also be used as such for the reaction in the next step without isolation.




3) Process of Producing Compound o-2 from Compound o-11




Compound o-2 can be produced by reacting compound o-11 in a solvent in the presence of a base.




Kind of base: inorganic bases such as sodium hydride and potassium carbonate; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10moles relative to 1 mole of compound o-11




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; sulfur compound such as dimethylsulfoxide; and mixtures thereof




Reaction temperature: room temperature to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound o-2 can also be used as such for the reaction in the next step without isolation.




4) Process of Producing Compound o-3 from Compound o-2




Compound o-3 can be produced by reacting compound o-2 with compound o-6 of the general formula:






M


9


—E


27


  o-6






wherein E


27


is as defined above and M


9


is iodine, bromine, chlorine, methanesulfonyloxy, or 2,4-dinitrophenoxy, in a solvent in the presence of a base.




Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound o-2




Kind of base: inorganic bases such as sodium hydride, potassium carbonate, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound o-2




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 15




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, D


7


, E


25


, E


26


, E


27


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-41466, or for example, by the following processes.




1) Process of Producing Compound p-1 from Compound a-1




Compound p-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).




2) Process of Producing Compound p-2 from Compound p-1




Compound p-2 can be produced by reacting compound p-1 with compound p-7 of the general formula:











wherein E


25


, E


26


, and R


209


are as defined above, in a solvent in the presence of a base.




Amount of compound p7: 0.9 to 10 moles relative to 1 mole of compound p-1




Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.




Reaction temperature: −40° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound p-2 can also be used as such for the reaction in the next step without isolation.




3) Process of Producing Compound p-3 from Compound p-2




Compound p-3 can be produced by reacting compound p-2 with compound o-6 of the general formula:






M


9


—E


27


  o-6






wherein E


27


and M


9


are as defined above, in a solvent in the presence of a base.




Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound p-2




Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-2




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 16




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, D


7


, E


25


, E


26


, E


27


, T, A, and Y as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-41466, or for example, by the following processes.




1) Process of Producing Compound p-4 from Compound p-1




Compound p-4 can be produced by reacting compound p-1 with ammonia in a solvent.




Amount of ammonia: 1 mole to large excess relative to 1 mole of compound p-1




Solvent: water, methanol, ethanol, tetrahydrofuran, 1,4-dioxane, etc.




Reaction temperature: −20° C. to 100° C.




Reaction time: a moment to 24 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound p-2 from Compound p-4




Compound p-2 can be produced by reacting compound p-4 with compound p-9 of the general formula:











wherein E


25


, E


26


, and R


209


are as defined above and R


210


is methyl, in a solvent in the presence of a base.




Amount of compound p-9: 0.9 to 10 moles relative to 1 mole of compound p-4




Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-4




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: room temperature to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound p-2 can also be used as such for the reaction in the next step without isolation.




3) Process of Producing Compound p-3 from Compound p-2




Compound p-3 can be produced by reacting compound p-2 with compound o-6 of the general formula:






M


9


—E


27


  o-6






wherein E


27


and M


9


are as defined above, in a solvent in the presence of a base.




Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound p-2




Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-2




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 17




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, D


7


, E


28


, E


29


, A, T, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-92943, or for example, by the following processes.




1) Process of Producing Compound p-6 from Compound p-5




Compound p-6 can be produced by reducing compound p-5 in a solvent.




Kind of reducing agent: NaBH


4


etc.




Amount of reducing agent: 1 to 10 moles relative to 1 mole of compound p-5




Solvent: water, methanol, ethanol, acetic acid, etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 18




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


30


, E


31


, E


42


, T, A, and Y are as defined above, and R


211


is hydrogen, methyl, or ethyl.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 9-323977 and WO98/17632, or for example, by the following processes.




1) Process of Producing Compound w-1 from Compound a-1




Compound w-1 can be produced from compound a-1 according to the process as described above in Producing Process 5, Step 1).




2) Process of Producing Compound w-2 from Compound w-1




Compound w-2 can be produced by reacting compound w-8 of the general formula:











wherein E


30


and E


42


are as defined above and M


10


is iodine, bromine, or chlorine, with water in the presence of a base to form compound w-9 of the general formula:











wherein E


30


and E


42


are as defined above (reaction 1), and then reacting the carbonyl derivative with compound w-1 (reaction 2).




(Reaction 1)




Reaction 1 is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 100° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 2 moles of each of the water and base relative to 1 mole compound w-8, which is ideal but can be freely changed depending upon the reaction conditions.




As the base to be used, both organic bases and inorganic bases can be used, examples of which are sodium acetate and potassium acetate.




The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof




(Reaction 2)




Reaction 2 is usually carried out in a solvent. The reaction temperature is usually in the range of −20° C. to 200° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of compound w-1 relative to 1 mole of compound w-8, which is ideal but can be freely changed depending upon the reaction conditions. Depending upon the conditions, salts of compound w-1, such as hydrochloride salt and sulfate salt, can also be used.




The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound w-3 from Compound w-2 (Route 1)




Compound w-3 can be produced by reacting compound w-2 with phosphorane compound w-10 of the general formula:











wherein E


31


is as defined above; R


213


is methyl or ethyl; and Ar is optionally substituted phenyl (e.g., phenyl), in a solvent.




This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of −20° C. to 150° C, preferably 0° C. to 100° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of compound w-10 relative to 1 mole of compound w-2, which is ideal but can be freely changed depending upon the reaction conditions.




The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound w-4 from Compound w-2 (Route 2)




Compound w-4 can be produced by reacting compound w-2 with compound w-11 of the general formula:











wherein E


31


and R


211


are as defined above, in the presence of a base.




This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 200° C., preferably 40° C. to 150° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are usually 1 to 10 moles of compound w-11, preferably 1 to 2 moles of compound w-11, which is ideal, relative to 1 mole of compound w-2. The amount of base is usually 1 mole to large excess, preferably 1 to 10 moles, relative to 1 mole of compound w-11




The base which can be used may include organic bases such as triethylamine and tributylamine.




The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining he desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




5) Process of Producing Compound w-3 from Compound w-4




Compound w-3 can be produced by reacting compound w-4, if necessary, in the presence of a base or acid, or in an acid-base mixed system.




This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 200° C., preferably 40° C. to 150° C. The reaction time is usually in the range of a moment to 96 hours.




The kind of base used, if necessary, may include organic bases such as pyridine; and metal alcoholates such as sodium methylate. The amount of base is usually 1 mole to large excess, preferably 1 to 10 moles, which is ideal, relative to 1 mole of compound w-4.




The kind of add used, if necessary, may include organic acids such as acetic acid and benzoic acid; and p-toluenesulfonic acid. The amount of acid is usually 1 mole to large excess, preferably 1 to 10 moles, which is ideal, relative to 1 mole of compound w-4.




The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound w-7 (i.e., compound w-2 wherein E


42


is H) can also be produced according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


30


, T, A, and Y are as defined above, and R


214


is methyl or ethyl.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 9-323977, or for example, by the following processes.




6) Process of Producing Compound w-5 from Compound a-1 (see Tetrahedron, vol. 35, p. 2013 (1979))




Compound w-5 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in a solvent in the presence of an acid, and then reacting the diazonium salt with compound w-12 of the general formula:











wherein E


30


and R


214


are as defined above, in a solvent in the presence of a base.




(Diazonium salt formation)




Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1




Kind of acid: hydrochloric acid etc.




Amount of acid: 1 to 100 moles relative to 1 mole of compound a-1




Solvent: water, ethanol, hydrochloric acid, etc.




Reaction temperature: −15° C. to room temperature




Reaction time: a moment to 24 hours




(Reaction with compound w-12)




Amount of compound w-12: 1 to 5 moles relative to 1 mole of compound a-1




Kind of base: sodium acetate etc.




Amount of base: 0.8 to 3 moles relative to 1 mole of acid used in the forgoing step




Solvent: ethanol, water, etc.




Reaction temperature: 0° C. to 60° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




6) Process of Producing Compound w-6 from Compound w-5




Compound w-6 can be produced by reacting compound w-5 in a solvent in the presence of a base.




The reaction temperature is usually in the range of 0° C. to 150° C.




The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of base relative to 1 mole of compound w-5, which is ideal but can be freely changed, if necessary. The base may include inorganic bases such as sodium hydroxide, lithium hydroxide, lithium hydroxide monohydrate, barium hydroxide, and potassium hydroxide.




The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; nitrites such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




7) Process of Producing Compound w-7 from Compound w-6




Compound w-7 can be produced by heating compound w-6 in a solvent.




The reaction temperature is usually in the range of 50° C. to 200° C. The reaction time is usually in the range of a moment to 72 hours.




The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; nitrites such as acetonitrile; amides such as N,N-dimethylformamride; alcohols such as methanol, ethanol and isopropanol; nitrogen-containing aromatic compounds such as pyridine and picoline; sulfur compounds such as dimethylsulfoxide; tertiary amines such as N,N-dimethylailine; water; and mixtures thereof.




In this reaction, metals such as copper powder may be used as a catalyst, if necessary.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 19




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


32


, E


33


, E


43


, T, A, and Y are as described above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-25186, or for example, by the following processes.




1) Process of Producing Compound r-1 from Compound a-1




Compound r-1 can be produced by converting compound a-1 into an isothiocyanate derivative in a solvent or without solvent.




Agent for conversion into isothiocyanate derivatives: thiophosgene etc.




Amount of agent for conversion into isothiocyanate derivatives: 1 equivalent to an excess amount relative to 1 mole of compound a-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.




Reaction temperature: room temperature to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound r-2 from Compound r-1




Compound r-2 can be produced by reacting compound r-1 with compound r-6 of the general formula:











wherein E


32


and E


43


are as defined above and R


215


is methyl, ethyl, or propyl in a solvent in the presence of a base.




Amount of compound r-6: 0.9 to 10 moles relative to 1 mole of compound r-1




Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound r-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chrormatography.




3) Process of Producing Compound r-3 from Compound r-2




Compound r-3 can be produced by reacting compound r-2 with Raney nickel in a solvent in the presence of a base.




Amount of Raney nickel: 1 to 20 moles relative to 1 mole of compound r-2




Kind of base: nitrogen-containing compounds such as pyridine; organic bases such as triethylamine; ammonia; etc.




Amount of base: 0. 1 to 20 moles relative to compound r-2




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound r-4 from Compound r-3




Compound r-4 can be produced by reacting compound r-3 in a solvent in the presence of a base.




Kind of base: metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 1 to 20 moles relative to compound r-3




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.




Reaction temperature: 20° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




5) Process of Producing Compound r-5 from Compound r-4




Compound r-5 can be produced by reacting compound r-4 with an acylating agent selected from compound r-7 of the general formula:











wherein E


33


is as defined above, or compound r-8 of the general formula:











wherein E


33


is as defined above, in a solvent.




Amount of acylating agent: 1 to 5 moles relative to 1 mole of compound r-4




Solvent: organic acids such as acetic acid and propionic acid; etc.




Reaction temperature: the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 20




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, E


34


, T, A, and Y are as defined above.




The reaction can be carried out, for example, according to the process as described in JP-A 4-356463, or for example, by the following process.




1) Process of Producing Compound s-1 from Compound a-1




Compound s-1 can be produced by reacting compound a-1 with acid anhydride s-2 of the general formula:











wherein E


34


is as defined above, in a solvent, if necessary, in the presence of an acid.




Amount of acid anhydride s-2: 1 to 5 moles relative to 1 mole of compound a-1




Solvent: organic acids such as acetic acid and propionic acid; aromatic hydrocarbons such as benzene and toluene; etc.




Kind of acid: p-toluenesulfonic acid etc.




Reaction temperature: room temperature to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 21




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, D


9


, V


1


, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 5-25173, or for example, by the following processes.




1) Process of Producing Compound t-1 from Compound a-1




Compound t-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).




2) Process of Producing Compound t-2 from Compound t-1




Compound t-2 can be produced by reacting compound t-1 with compound t-3 of the general formula:











wherein V


1


is as defined above, in a solvent in the presence of a base.




Amount of compound t-3: 0.9 to 10 moles relative to 1 mole of compound t-1




Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound t-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.




Reaction temperature: −40° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 22




This is the producing process according to the following schemes:



















wherein R


1


, R


2


, R


3


, R


4


, E


35


, A, T, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, according to the processes as described in WO98/14452, or for example, by the following processes.




1) Process of Producing Compound u-1 from Compound a-1




Compound u-1 can be produced from compound a-1 according to the process as described above in Producing Process 19, Step 1).




2) Process of producing compound u-2 from Compound u-1




Compound u-2 can be produced by reacting compound u-1 with compound u-12 of the general formula:











wherein E


35


and R


215


are as defined above, in a solvent in the presence of a base.




Amount of compound u-12: 0.9 to 10 moles relative to 1 mole of compound u-1




Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 0.1 to 10 moles relative to 1 mole of compound u-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated,. thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound u-3 from Compound u-2




Compound u-3 can be produced by reacting compound u-2 with a methylating agent such as methyl iodide or dimethyl sulfate in a solvent in the presence of a base.




Kind of base: organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; inorganic bases such as sodium hydride, potassium carbonate, and potassium hydroxide; etc.




Amount of base: 1 to 20 moles relative to 1 mole of compound u-2




Amount of methylating agent: 1 to 20 moles relative to 1 mole of compound u-2




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; water; and mixtures thereof; etc.




Reaction temperature: −10° C. to room temperature




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound u-4 from Compound u-3




Compound u-4 can be produced by reacting compound u-3 with an oxidizing agent in a solvent.




Kind of oxidizing agent: m-chloroperbenzoic acid, aqueous hydrogen peroxide, etc.




Amount of oxidizing agent: 2 to 20 moles relative to 1 mole of compound u-3




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; water; and mixtures thereof; etc.




Reaction temperature: −20° C. to room temperature




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




5) Process of Producing Compound u-5 from Compound u-4




Compound u-5 can be produced by reacting compound u-4 with ammonia in a solvent.




Amount of ammonia: 1 mole to large excess relative to 1 mole of compound u-4




Solvent: t-butanol, isopropanol, etc.




Reaction temperature: −20° C. to 40° C.




Reaction time: a moment to 10 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




6) Process of Producing Compound u-6 from Compound u-4




Compound u-6 can be produced by reacting compound u-4 with an azidizing agent such as sodium azide or trimethylsilyl azide in a solvent such as methanol, ethanol, and water.




Amount of azidizing agent: 1 equivalent to an excess amount relative to 1 mole of compound u-4




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




7) Process of Producing Compound u-7 from Compound u-5




Compound u-7 can be produced by reacting compound u-5 with a haloacetaldehyde such as chloroacetaldehyde (40% aqueous solution) in a solvent.




The amount of haloacetaldehyde is 1 equivalent to an excess amount relative to 1 mole of compound u-5. The solvent may include ethers such as 1,4-dioxane and tetrahydrofuran; water; and mixtures thereof; etc. The reaction temperature is in the range of 40° C. to the reflux temperature of the solvent. The reaction time is in the range of a moment to 20 hours.




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining he desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




8) Process of Producing Compound u-8 from Compound u-4




Compound u-8 can be produced by reacting compound u-4 with hydrazine (hydrate) in a solvent or without solvent.




Amount of hydrazine: 1 mole to a large excess amount relative to 1 mole of compound u-4




Solvent: t-butanol, isopropanol, etc.




Reaction temperature: −20° C. to 40° C.




Reaction time: a moment to 10 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




9) Process of Producing Compound u-9 from Compound u-4




Compound u-9 can be produced by reacting compound u-4 with 2-ethanolamine in a solvent or without solvent.




Amount of 2-ethanolamine: 1 mole to a large excess amount relative to 1 mole of compound u-4




Solvent: t-butanol, isopropanol, etc.




Reaction temperature: −20° C. to 40° C.




Reaction time: a moment to 10 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




10) Process of Producing Compound u-10 from Compound-u-8




Compound u-10 can be produced by reacting compound u-8 with formic acid in a solvent or without solvent, if necessary, in the presence of another acid.




Kind of acid: p-toluenesulfonic acid, hydrochloric acid, etc.




Amount of acid: 0.001 mole to a large excess amount relative to 1 mole of compound u-8




Amount of formic acid: 1 mole to a large excess amount to 1 mole of compound u-8




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N-N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof, etc.




Reaction temperature: 40° C. to the reflux temperature of the solvent




Reaction time: a moment to 10 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




11) Process of Producing Compound u-11 from Compound u-9




Compound u-11 can be produced by reacting compound u-9 in a solvent or without solvent in the presence of an acid.




Kind of acid: p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, polyphosphoric acid, etc.




Amount of acid: 0.001 mole to a large excess amount relative to 1 mole of compound u-9




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N-N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.




Reaction temperature: 40° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 23




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, R


25


, E


32


, E


33


, E


43


, T, A, and Y are as defined above; and R


216


is C


1


-C


6


alkoxy (e.g., methoxy, ethoxy) or NR


217


(R


218


(e.g., dimethylamino, dimethylamino) wherein R


217


and R


218


are independently C


1


-C


5


alkyl.




The reactions in the respective steps can be carried out, for example, according to the processes as described in Bull. Soc. Chim. Fr. (134, pp. 47-57, 1997), or for example, by the following processes.




1) Process of Producing Compound r-9 from Compound r-6




Compound r-9 can be produced by reacting compound r-6 with compound r-10 of the general formula:











wherein E


33


and R


216


are as defined above; R


219


and R


220


are independently C


1


-C


6


alkyl (e.g., methyl, ethyl), in a solvent, if necessary, in the presence of an acid.




Amount of compound r-10: 1 mole to an excess amount relative to 1 mole of compound r-6




Kind of acid: organic acids such as acetic acid and p-toluenesulfonic acid




Amount of acid: a catalytic amount to large excess relative to 1 mole of compound r-6




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours,




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound r-5 from Compound r-9




Compound r-5 can be produced by reacting compound r-9 with compound a-1 in a solvent, if necessary, in the presence of an acid.




Amount of compound a-1: 0.9 to 1.1 moles relative to 1 mole of compound r-9




Kind of acid: organic acids such as acetic acid and p-toluenesulfonic acid




Amount of acid: a catalytic amount to large excess relative to 1 mole of compound r-9




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Depending upon the kinds of R


1


, R


2


, R


3


, R


4


, Y, T, and A, the formation of Q may be followed by the introduction or formation of R


1


, R


2


, R


3


, R


4


, Y, T, and A. In these producing processes, protective groups may be used, if necessary, for the protection, of functional groups from the reactions. (see “Protective Groups in Organic Synthesis” written by T. W. Greene.) The following are examples of these producing processes.




PRODUCING PROCESS 24




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, Y


11


, and Q are as defined above; R


221


is methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, aminocarbonyl, or nitrile; and M


23


is fluorine, chlorine, or bromine.




The reactions in the respective steps can be carried out, for example, by the following processes.




1) Process of Producing Compound z-2 from Compound z-1




Compound z-2 can be produced by reacting with compound z-1 in a solvent in the presence of a base or acid, and, if necessary, in the presence of a phase transfer catalyst.




Kind of base: inorganic bases such as sodium hydroxide, potassium hydroxide, and lithium hydroxide; etc.




Amount of base: 0.9 to 10 moles relative to 1 mole of compound z-1




Kind of acid: hydrochloric acid, sulfuric acid, etc.




Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-1




Kind of phase transfer catalyst: tetrabutylammonium bromide etc.




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound z-3 from Compound z-2




Compound z-3 can be produced by heating compound z-2 in a solvent, if necessary, in the presence of an acid or base.




Kind of base: nitrogen-containing compounds such as quinoline and pyridine; amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; and mixtures thereof; etc.




Amount of base: 0.9 mole to an excess amount relative to 1 mole of compound z-2




Kind of acid: hydrochloric acid, sulfuric acid, etc.




Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-2




Kind of phase transfer catalyst: tetrabutylammonium bromide etc.




Solvent: amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; and mixtures thereof; etc.




Reaction temperature: 50° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




In this process, metal catalysts such as copper may be used in their catalytic amounts.




3) Process of Producing Compound z-24 from Compound z-23




Compound z-24 can be produced by reducing compound z-23 with iron powder in a solvent.




Amount of iron powder: 2 to 10 moles relative to 1 mole of compound z-23




Solvent: acetic acid, water, and mixtures thereof, etc.




Reaction temperature: 15° C. to 110° C.




Reaction time: a moment to 100 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound z-25 from Compound z-24




Compound z-25 can be produced by converting compound z-24 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with copper halide such as copper (I) chloride or copper (I) bromide.




(Diazonium salt formation)




Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-24




Kind of acid: sulfuric acid, hydrochloric acid, etc.




Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-24




Solvent: water, ethanol, hydrochloric acid, etc.




Reaction temperature: −15° C. to room temperature




Reaction time: a moment to 24 hours




(Reaction with copper halide)




Kind of copper halide: copper (C) chloride, copper (I) bromide, etc.




Amount of copper halide: 1 to 10 moles relative to 1 mole of compound z-24




Solvent: hydrochloric acid, hydrobromic acid, etc.




Reaction temperature: −10° C. to 80° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




5) Process of Producing Compound z-3 from Compound z-24




Compound z-3 can be produced by converting compound z-24 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt in a solvent.




(Diazonium salt formation)




Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-24




Kind of acid: sulfuric acid, hydrochloric acid, etc.




Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-24




Solvent: water, ethanol, hydrochloric acid, etc.




Reaction temperature: −15° C. to room temperature




Reaction time: a moment to 24 hours




(Thermal decomposition).




Solvent: sulfuric acid, water, etc.




Reaction temperature: room temperature to 200° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 25




This is the producing process according to the following scheme:











wherein R


1


, R


3


, R


4


, R


11


, Q, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, by the following processes.




1) Process of Producing Compound z-5 from Compound z-4




Compound z-5 can be produced by demethylating compound z-4 in a solvent in the presence of an acid or trimethylsilane iodide.




Kind of acid: inorganic acids such as hydrochloric acid and sulfuric acid; Lewis acids such as boron tribromide and aluminum chloride; etc.




Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-4




Amount of trimethylsilane iodide: 1 mole to an excess amount relative to 1 mole of compound z-4




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 168 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound z-6 from Compound z-5




Compound z-6 can be produced by reacting compound z-5 with compound z-18 of the general formula:






M


9


—R


11


  z-18






wherein M


9


and R


11


are as defined above, in a solvent in the presence of a base.




Amount of compound z-18: 1 to 2 moles relative to 1 mole of compound z-5




Kind of base: potassium carbonate, sodium hydride, etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound z-5




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: −10° C. to 100° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 26




This is the producing process according to the following scheme:











wherein R


1


, R


4


, Q, T, A, and Y are as defined above; R


222


is —OR


11


or —SR


12


wherein R


11


and R


12


are as defined above; and R


223


is —OR


224


or —SR


225


wherein R


224


and R


225


are the same or different and independently hydrogen, C


1


-C


10


alkyl, C


3


-C


10


cycloalkyl, C


3


-C


10


cycloalkyl C


1


-C


3


alkyl, C


3


-C


10


alkenyl; C


3


-C


10


alkynyl, C


1


-C


5


alkoxy C


1


-C


5


allkyl, C


1


-C


5


alkylthio C


1


-C


5


alkyl, or optionally substituted phenyl.




The reactions in the respective steps can be carried out, for example, by the following processes.




1) Process of Producing Compound z-8 from Compound z-7




Compound z-8 can be produced by reacting compound z-19 of the general formula:






H—R


222


  z-19






wherein R


222


is as defined above, in a solvent in the presence of a base.




Amount of compound z-19: 1 to 5 moles relative to 1 mole of compound z-7




Kind of base: organic bases such as triethylamine, inorganic bases such as potassium carbonate and sodium hydride; alkoxides such as sodium methoxide and sodium thiomethoxide; etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound z-7




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof, etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours;




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound z-8 wherein R


222


is —OR


224


or —SR


225


; and R


224


and R


224


are as defined above (hereinafter referred to as compound z-8′) can be used to produce compound z-9 or compound z-10 as shown in the following processes.




2) Process of Producing Compound z-9 from Compound z-8′




Compound z-9 can be produced by reducing compound z-8′ with iron powder in a solvent.




Amount of iron powder: 2 to 10 moles relative to 1 mole of compound z-8′




Solvent: acetic acid, water, and mixtures thereof; etc.




Reaction temperature: 15° C. to 110° C.




Reaction time: a moment to 100 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound z-10 from Compound z-9




Compound z-10 can be produced by converting compound z-9 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with a chloride such as copper (I) chloride.




(Diazonium salt formation)




Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-9




Kind of acid: hydrochloric acid, etc.




Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-9




Solvent: water, ethanol, hydrochloric acid, etc.




Reaction temperature: −15° C. to room temperature




Reaction time: a moment to 24 hours




(Reaction with chloride)




Kind of chloride: copper (a) chloride etc.




Amount of chloride: 1 to 10 moles relative to 1 mole of compound z-9




Solvent: hydrochloric acid etc.




Reaction temperature: −10° C. to 80° C.




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




PRODUCING PROCESS 27




This is the producing process according to the following process:











wherein R


1


, R


3


, R


4


, R


14


, R


17


, R


19


, Q, T, A, and Y are as defined above.




The reactions in the respective steps can be carried out, for example, by the following processes.




1) Process of Producing Compound z-12 from Compound z-11




Compound z-12 can be produced by reacting compound z-11 with copper (I) cyanide in a solvent.




Amount of copper (I) cyanide: 1 to 4 moles relative to 1 mole of compound z-11




Kind of solvent: amides such as N,N-dimethylformamide and N-methylpyrrolidone; sulfur compound such as dimethylsulfoxide; etc.




Reaction temperature: 40° C. to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound z-13 from Compound z-12




Compound z-13 can be produced by reacting compound z-12 with water in the presence of an acid.




Amount of water: 1 mole to an excess amount relative to 1 mole of compound z-12




Kind of acid: hydrochloric acid, sulfuric acid, etc.




Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-12




Reaction temperature: 10° C. to 50° C.




Reaction time: a moment to 24 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound z-14 from Compound z-13




Compound z-14 can be produced by reacting compound z-13 with water in the presence of an acid or base.




Amount of water: 1 equivalent to an excess amount relative to 1 mole of compound z-13




Kind of acid: hydrochloric acid, sulfuric acid, etc.




Amount of acid: 1 equivalent to an excess amount relative to 1 mole of compound z-13




Kind of base: sodium hydroxide, potassium hydroxide, etc.




Amount of base: 1 to 3 equivalents relative to 1 mole of compound z-13




Reaction temperature: room temperature to 150° C.




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound z-17 from Compound z-14




Compound z-17 can be produced by reacting compound z-14 with thionyl chloride to form an acid chloride compound (reaction 1) and then reacting the acid chloride compound with compound z-20 of the general formula:






HO—R


14


  z-20






wherein R


14


is as defined above, in a solvent in the presence of a base (reaction 2).




(Reaction 1)




Amount of thionyl chloride: 1 mole to an excess amount relative to compound z-14




Reaction temperature: 40° C. to the reflux temperature of thionyl chloride




Reaction time: a moment to 10 hours




After completion of the reaction, the reaction mixture was concentrated and used as the starting material for reaction 2.




(Reaction 2)




Amount of compound z-20: 1 mole to an excess amount relative to 1 mole of compound z-14




Kind of base: pyridine, triethylamine, potassium carbonate, etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound z-14




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




5) Process of Producing Compound z-17 from Compound z-13




Compound z-17 can be produced by reacting compound z-13 with compound z-20 of the general formula:






HO—R


14


  z-20






wherein R


14


is as defined above, in a solvent in the presence of a boron trihalide compound.




Amount of compound z-20: 1 mole to an excess amount relative to 1 mole of compound z-13




Kind of boron trihaihde compound: boron trifluoride, boron trichloride, boron tribromide, etc.




Amount of boron trihalide compound: 1 mole to an excess amount relative to 1 mole of compound z-13




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 50° C. to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




6) Process of Producing Compound z-15 from Compound z-12




Compound z-15 can be produced by reacting compound z-12 with compound z-2 1 of the general formula:






M


11


—Mg—R


17


  z-21






wherein R


17


is as defined above and M


11


is chlorine or bromine, in a solvent.




Amount of compound z-21: 1 to 1.3 moles relative to 1 mole of compound z-12




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




7) Process of Producing Compound z-16 from Compound z-15




Compound z-16 can be produced by reacting compound z-15 with compound z-22 of the general formula:






R


19


ONH


2


  z-22






wherein R


19


is as defined above, in a solvent, if necessary, in the presence of a base.




Amount of compound z-22: 1 to 3 moles relative to 1 mole of compound z-15




Kind of base: triethylamine, pyridine, potassium carbonate, etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound z-15




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




In addition to the above processes, the present compounds can also be produced by making reference to, for example, JP-A 5-213970, EP 683160-A1, and JP-A 61-161288.




The processes of producing some of the starting materials used in the production of the present compounds are explained below.




REFERENCE PRODUCING PROCESS 1




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, and Y


11


are as defined above; and R


250


is carboxy, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, or nitrile.




The reactions in the respective steps can be carried out, for example, according to the processes as described in Indian Journal of Chemistry. (vol. 20B, pp. 391-393, 1981), Indian Journal of Chemistry (vol. 14B, pp. 6886-6891, 1981), Organic Syntheses (vol. 33, p. 43, 1953), or for example, by the following processes.




1) Process of Producing Compound v-2 from Compound v-1




Compound v-2 can be produced by reacting compound v-1 with compound v-19 of the general formula:











wherein R


250


is as defined above and M


20


is chlorine, bromine, or iodine, in a solvent in the presence of a base.




Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound v-1




Amount of compound v-19: 0.9 to 3 moles relative to 1 mole of compound v-1




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof, etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound v-3 from Compound v-2




Compound v-3 can be produced by reacting compound v-2 in a solvent in the presence of a base.




Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 1 to 10 moles relative to 1 mole of compound v-2




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound v-4 from Compound v-3




Compound v-4 can be produced by reacting compound v-3 in a solvent in the presence of a base or acid and, if necessary, in the presence of a phase transfer catalyst.




Kind of base: inorganic bases such as sodium hydroxide and potassium hydroxide; etc.




Amount of base: 0.9 to 10 moles relative to 1 mole of compound v-3




Kind of acid: hydrochloric acid, sulfuric acid, etc.




Amount of acid: 1 mole to an excess amount relative to 1 mole of compound v-3




Kind of phase transfer catalyst: tetrabutylammonium bromide etc.




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.




Reaction temperature: 10° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




4) Process of Producing Compound v-5 from Compound v-4




Compound v-5 can be produced by heating compound v-4 in a solvent, if necessary, in the presence of a base or acid.




Kind of base: nitrogen-containing compounds such as quinoline and pyridine; amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; and mixtures thereof; etc.




Amount of base: 0.9 mole to an excess amount relative to 1 mole of compound v-4




Kind of acid: hydrochloric acid, sulfuric acid, etc.




Amount of acid: 1 mole to an excess amount relative to 1 mole of compound v-4




Solvent: amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; and mixtures thereof, etc.




Reaction temperature: 50° C. to the reflux temperature of the solvent




Reaction time: a moment to 96 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




In this process, metal catalysts such as copper may be used.




Compound v-1 as the starting material in this producing process can also be produced from the corresponding benzaldehyde derivative by making reference to, for example, Shin Jikken Kagaku Koza (published by Maruzen Kabushiki Kaisha) vol. 14, pp. 1466-1470. The benzaldehyde derivative to be used as the starting material at that time can also be produced by making reference to, for example, EP 0312338-A1, Synthetic Communication, 24(12), pp. 1757-1760 (1994), and J. Chem. Soc. Perkin I, pp. 318-321 (1978).




Compound v-2 as the intermediate can also be produced according to the following scheme 1 or 2.











wherein R


1


, R


2


, R


3


, R


4


, R


250


, and Y


11


are as defined above; and M


21


is fluorine, chlorine, or bromine.




5) Process of Producing Compound v-2 from Compound v-6




Compound v-2 can be produced by reacting compound v-6 with compound v-17 of the formula:











wherein Y


11


and R


250


are as defined above, in a solvent in the presence of a base.




Kind of base: inorganic bases such as potassium carbonate, sodium hydride, sodium hydroxide, and potassium fluoride; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; etc.




Amount of base: 1 to 10 moles relative to 1 mole of compound v-6




Amount of compound v-17: 0.9 to 10 moles relative to 1 mole of compound v-6




Solvent: aromatic hydrocarbons such as benzene and toluene; halo-genated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; and mixtures thereof; etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 72 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.











wherein R


1


, R


2


, R


3


, R


4


, R


250


, and Y


11


are as defined above.




1) Process of Producing Compound v-2 from Compound v-16




Compound v-2 can be produced by reacting compound v-16 with copper (I) cyanide in a solvent.




Amount of copper (I) cyanide: 1 to 4 moles relative to 1 mole of compound v-16




Kind of solvent: amides such as N,N-dimethylformamide and N-methylpyrrolidone; sulfur compound such as dimethylsulfoxide; etc.




Reaction temperature: 40° C. to the reflux temperature of the solvent




Reaction time: a moment to 120 hours




After completion of the reaction, ammonia water is added, if necessary, to the reaction mixture, which is then extracted with an organic solvent, and the organic layer is dried and concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




REFERENCE PRODUCING PROCESS 2




This is the producing process according to the following scheme:











wherein R


1


,


2


, R


3


, and R


4


are as defined above; and M


22


is fluorine or chlorine.




The reactions in the respective steps can be carried out, for example, according to the processes as described in Tetrahedron Letters (vol. 37, No. 17, pp. 2885-2886, 1996), or for example, by the following processes.




1) Process of Producing Compound v-8 from Compound v-7




Compound v-8 can be produced by reacting compound v-7 with aceto-hydroxamic acid in a solvent in the presence of a base.




Amount of hydroxamic acid: 1 to 3 moles relative to 1 mole of compound v-7




Kind of base: potassium t-butoxide, sodium hydride, etc.




Amount of base: 1 to 3 moles relative to 1 mole of compound v-7




Solvent: N,N-dimethylformamide, dimethylsulfoxide, tetrahydrofuran, etc.




Reaction temperature: room temperature to 100° C.




Reaction time a moment to 100 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




REFERENCE PRODUCING PROCESS 3




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, and R


4


are as defined above; Y


1


is oxygen, sulfur, or N-R


142


; and R


142


is as defined above.




The reactions in the respective steps can be carried out, for example, by the following processes.




1) Process of Producing Compound v-10 from Compound v-9




Compound v-10 can be produced by reacting compound v-9 with a nitrating agent in a solvent or without solvent.




Kind of nitrating agent: nitric acid etc.




Amount of nitrating agent: 1 to 1.5 moles relative to 1 mole of compound v-9




Solvent: acetic anhydride etc.




Reaction temperature: −10° C. to 50° C.




Reaction time: a moment to 100 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound v-11 from Compound v-10




Compound v-11 can be produced by reducing compound v-10 with iron powder in a solvent.




Amount of iron powder: 1 to 10 moles relative to 1 mole of compound v-10




Solvent: acetic acid, water, and mixtures thereof, etc.




Reaction temperature: 15° C. to 110° C.




Reaction time: a moment to 100 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




REFERENCE PRODUCING PROCESS 4




This is the producing process according to the following scheme:











wherein R


226


is C


1


-C


10


alkyl and M


12


is fluorine or chlorine.




The reactions in the respective steps can be carried out, for example, according to the processes as described in Khim. Geterotsikl. Soedin (1990, Issue 5, pp. 597-600), Khim. Geterotsikl. Soedin (1989, Issue 5, pp. 704), or for example, by the following processes.




1) Process of Producing Compound v-13 from Compound v-12




Compound v-13 can be produced by reacting compound v-12 with nitroenamine compound v-18 of the formula:











in a solvent and, if necessary, in the presence of an acid.




Amount of compound v-18: 1 to 3.0 moles relative to 1 mole of compound v-12




Kind of acid: acetic acid, p-toluenesulfonic acid, sulfuric acid, etc.




Amount of acid: a catalytic amount to a large excess amount relative to 1 mole of compound v-12




Solvent: aromatic hydrocarbons such as toluene and xylene; ethers such as tetrahydrofuran; organic acids such as acetic acid and propionic acid; amides such as N,N-dimethylformamide; and mixtures thereof; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 100 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




2) Process of Producing Compound v-14 from Compound v-13




Compound v-14 can be produced by reacting compound v-13 with an alkylcarbonylating agent in a solvent and, if necessary, in the presence of an acid and a base.




Kind of alkylcarbonylating agent: acetic anhydride, acetyl chloride, etc.




Amount of alkylcarbonylating agent: 1 to 2.0 moles relative to 1 mole of compound v-13




Kind of acid: acetic acid, p-toluenesulfonic acid, sulfuric acid, etc.




Amount of acid: a catalytic amount to a large excess amount relative to 1 mole of compound v-13




Kind of base: sodium hydroxide, potassium carbonate, triethylamine, etc.




Amount of base: a catalytic amount to a large excess amount relative to 1 mole of compound v-13




Solvent: aromatic hydrocarbons such as toluene and xylene; ethers such as tetrahydrofuran; organic acids such as acetic acid and propionic add; inorganic acids such as sulfuric acid; amides such as N,N-dimethylformamide; and mixtures thereof; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 100 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




3) Process of Producing Compound v-15 from Compound v-14




Compound v-15 can be produced by reducing compound v-14 with iron powder in a solvent.




Amount of iron powder: 1 to 10 moles relative to 1 mole of compound v-14




Solvent: acetic acid, water, and mixtures thereof, etc.




Reaction temperature: 15° C. to 110° C.




Reaction time: a moment to 100 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




REFERENCE PRODUCING PROCESS 5




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, and A are as defined above; Y


2


is nitrogen or C—R


152


; and R


152


is as defined above.




The reaction can be carried out, for example, according to the processes as described in Synthesis (Issue 1, pp. 1-17, 1977), J. Med. Chem. (Vol. 39, pp. 570-581, 1996), or for example, by the following process.




1) Process of Producing Compound x-3 from Compound x-5




Compound x-3 can be produced by reacting compound x-5 with an aminating agent in a solvent in the presence of a base.




Kind of base: inorganic bases such as potassium carbonate, sodium hydride, sodium hydroxide, and potassium hydroxide; etc.




Amount of base: 1 to 20 moles relative to 1 mole to compound x-5




Kind of aminating agent: hydroxylamine=O-sulfonic acid, chloramine, O-(2,4-dinitrophenyl)hydroxylamine, etc.




Amount of aminating agent: 0.9 to 5 moles relative to 1 mole of compound x-5




Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof; etc.




Reaction temperature: −10° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




Compound x-5 used as the intermediate in the above reaction can be produced, for example, according to the processes as described in JP-A 7-508259, JP-A 7-508500, WO93/18008, and WO94/25446.




REFERENCE PRODUCING PROCESS 6




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, and Y


11


are as defined above.




The reaction can be carried out, for example, according to the process as described in Chem. Pharm. Bull. 32(11), pp. 4260-4270 (1984), or for example, by the following scheme:




1) Process of Producing Compound v-20 from Compound v-1




Compound v-20 can be produced by reacting compound v-1 with bromonitromethane in a solvent in the presence of a base.




Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; metal alcoholates such as sodium methylate and sodium ethylate; etc.




Amount of base: 1 to 5 moles relative to 1 mole of compound v-1




Amount of bromonitromethane: 0.9 to 3 moles realtive to 1 mole of compound v-1




Solvent: aromatic hydrocarbons such as benzene and toluene;




halogenated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof, etc.




Reaction temperature: 0° C. to the reflux temperature of the solvent




Reaction time: a moment to 48 hours




After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.




REFERENCE PRODUCING PROCESS 7




This is the producing process according to the following scheme:











wherein R


1


, R


2


, R


3


, R


4


, R


221


, Y


11


, and Q are as defined above.




The reactions in the respective steps can be carried out according to the processes as described in Producing Processes 1 to 23.




The benzonitrile derivatives used in Reference Producing Processes 1 and 2 can be produced from the corresponding benzaldehyde derivatives or benzamide derivatives. (see Shin Jikken Kagaku Koza, edited by Nihon Kagaku Kai, Maruzen Kabushiki Kaisha, 14, pp. 1466-1474)




Examples of the present compounds which can be prepared according to the above producing process are illustrated below; however, the present invention is not limited to these examples.




In the examples, Me indicates methyl; Et, ethyl; Pr, propyl; Bu, butyl; Pen, pentyl; Hex, hexyl; Hep, heptyl; Oct, octyl; i-, iso-; s-, sec-; c-, cyclo-; and groups not particularly indicated are in normal form.




Compounds of the general formulas:











































































































wherein




A's are selected from nitrogen or CH;




Y


1


's are selected from oxygen or sulfur;




Y


2


's are selected from nitrogen or CH,




R


2


's are selected from hydrogen, fluorine, chlorine, bromine, iodine, CH


2


OH, CHO, COOH, CONH


2


, COCl, SO


2


Cl, COGH


3


; SH, OH, NH


2


, NO


2


, CN, CH


3


, CH


2


Br, CHB


2


, CBr


3


, CH


2


F, CHF


2


, CF


3


, O-Me, O-Et, O-Pr, O-i-Pr, O-Bu, O-i-Bu, O-s-Bu, O-Pen, O-c-Pen, O-Hex, O-c-Hex, O-Hep, O-Oct, OCH


2


CH


2


F, OCH


2


CH


2


Cl, OCH


2


CH


2


Br, OCH


2


CF


3


, OCH


2


OCH


3


, OCH


2


CH


2


OCH


3


, OCH


2


CH


2


OCH


2


CH


3


, OCH


2


SCH


3


, OCH


2


CH


2


SCH


3


, OCH


2


CH


2


SCH


2


CH


3


, OCH


2


CH═CH


2


, OCH(CH


3


)CH═CH


2


, OC(CH


3


)


2


CH═CH


2


, OCH


2


C(Cl)═CH


2


, OCH(CH


3


)C(Cl)═CH


2


, OCH


2


C(CH


3


)═CH


2


, OCH


2


C≡CH, OCH(CH


3


)C≡CH, OC(CH


3


)


2


C≡CH, OCH


2


-c-Pr, OCH


2


-c-Pen, OCH


2


-c-Hex, OCH


2


CN, OCH(CH


3


)CN, OCOMe, OCOEt, OCOPr, OCO-i-Pr, OCOCF


3


, OCOCF


2


H, OCH


2


COOH, OCH


2


COOMe, OCH


2


COOEt, OCH


2


GOOPr, OCH


2


COO-i-Pr, OCH


2


COOBu, OCH


2


COO-s-Bu, OCH


2


COOPen, OCH


2


COOHex, OCH


2


COOHep, OCH


2


COO-c-Pen, OCH


2


COO-c-Hex, OCH


2


COOCH


2


CH═CH


2


, OCH


2


COOCH


2


C≡OCH, OCH


2


COOPh, OCH


2


COOCH


2


Ph, OCH


2


C(═NOMe)COOMe, OCH


2


C(═NOMe)COOEt, OCH


2


C(═NOMe)COOPr, OCH


2


COOCH


2


COOH, OCH


2


COOCH


2


COOMe, OCH


2


COOCH


2


COOEt, OCH


2


COOCH


2


COOPr, OCH


2


COOCH


2


COO-i-Pr, OCH


2


COOCH


2


COOBu, OCH


2


COOCH


2


COO-c-Pen, OCH


2


COOCH


2


COO-c-Hex, OCH


2


COOCH


2


COOCH


2


CH═CH


2


, OCH


2


COOCH


2


COOCH


2


C≡CH, OCH


2


COOCH(CH


3


)COOH, OCH


2


COOCH(CH


3


)COOMe, OCH


2


COOCH(CH


3


)COOEt, OCH


2


COOCH(CH


3


)COOPr, OCH


2


COOCH(CH


3


)COO-i-Pr, OCH


2


COOCH(CH


3


)COOBu, OCH


2


COOCH(CH


3


)COO-c-Pen, OCH


2


COOCH(CH


3


)COO-c-Hex, OCH


2


COOCH(CH


3


)COOCH


2


CH═CH


2


, OCH


2


COOCH(CH


3


)COOCH


2


C≡CH, OCH


2


COOC(CH


3


)


2


COOH, OCH


2


COOC(CH


3


)


2


COOMe, OCH


2


COOC(CH


3


)


2


COOEt, OCH


2


COOC(CH


3


)


2


COOPr, OCH


2


COOC(CH


3


)


2


COO-i-Pr, OCH


2


COOC(CH


3


)


2


COOBu, OOH


2


COOC(CH


3


)


2


COO-c-Pen, OCH


2


COOC(CH


3


)


2


COO-c-Hex, OCH


2


COOC(CH


3


)


2


COOCH


2


CH═CH


2


, OCH


2


COOC(CH


3


)


2


COOCH


2


C≡CH, OCH(CH


3


)COOH, OCH(CH


3


)COOMe, OCH(CH


3


)COOEt, OCH(CH


3


)COOPr, OCH(CH


3


)COO-i-Pr, OCH(CH


3


)COOBu, OCH(CH


3


)COO-s-Bu, OCH(CH


3


)COOPen, OCH(CH


3


)COOHex, OCH(CH


3


)COOHep, OCH(CH


3


)COO-c-Pen, OCH(CH


3


)COO-c-Hex, OCH(CH


3


)COOCH


2


CH═CH


2


, OCH(CH


3


)COOCH


2


C≡CH, OCH(CH


3


)COOPh, OCH(CH


3


)COOCH


2


Ph, OCH(CH


3


)C(═NOMe)COOMe, OCH(CH


3


)C(═NOMe)COOEt, OCH(CH


3


)C(═NOMe)COOPr, OCH(CH


3


)COOCH


2


COOH, OCH(CH


3


)COOCH


2


COOMe, OCH(CH


3


)COOCH


2


COOEt, OCH(CH


3


)COOCH


2


COOPr, OCH(CH


3


)COOCH


2


COO-i-Pr, OCH(CH


3


)COOCH


2


COOBu, OCH(CH


3


)COOCH


2


COO-c-Pen, OCH(CH


3


)COOCH


2


COO-c-Hex, OCH(CH


3


)COOCH


2


COOCH


2


CH═CH


2


, OCH(CH


3


)COOH


2


COOCH


2


C≡CH, OCH(CH


3


)COOCH(CH


3


)COOH, OCH(CH


3


)COOH(CH


3


)COOMe, OCH(CH


3


)COOCH(CH


3


)COOEt, OCH(CH


3


)COOCH(CH


3


)COOPr, OCH(CH


3


)COOCH(CH


3


)COO-i-Pr, OCH(CH


3


)COOCH(CH


3


)COOBu, OCH(CH


3


)COOCH(CH


3


)COO-c-Pen, OCH(CH


3


)COOCH(CH


3


)COO-c-Hex, OCH(CH


3


)COOCH(CH


3


)COOCH


2


CH═CH


2


, OCH(CH


3


)COOCH(CH


3


)COOCH


2


C≡CH, OCH(CH


3


)COOC(CH


3


)


2


COOH, OCH(CH


3


)COOC(CH


3


)


2


COOMe, OCH(CH


3


)COOC(CH


3


)


2


COOEt, OCH(CH


3


)COOC(CH


3


)


2


COOPr, OCH(CH


3


)COOC(CH


3


)


2


COO-i-Pr, OCH(CH


3


)COOC(CH


3


)


2


COOBu, OCH(CH


3


)COOC(CH


3


)


2


COO-c-Pen, OCH(CH


3


)COOC(CH


3


)


2


COO-c-Hex, OCH(CH


3


)COOC(CH


3


)


2


COOCH


2


CH═CH


2


, OCH(CH


3


)COOC(CH


3


)


2


COOCH


2


C≡CH, OCH


2


CON(Me)


2


, OCH


2


CON(Et)


2


, OCH(CH


3


)CON(Me)


2


, OCH(CH


3


)CON(Et)


2


, S-Me, S-Et, S-Pr, S-i-Pr, S-Bu, S-i-Bu, S-s-Bu, S-Pen, S-c-Pen, S-Hex, S-c-Hex, S-Hep, S-Oct, SCH


2


CH


2


F, SCH


2


CH


2


Cl, SCH


2


CH


2


Br, SCH


2


CF


3


, SCH


2


OCH


3


, SCH


2


CH


2


OCH


3


, SCH


2


CH


2


OCH


2


CH


3


, SCH


2


SCH


3


, SCH


2


CH


2


SCH


3


, SCH


2


CH


2


SCH


2


CH


3


, SCH


2


CH═CH


2


, SCH(CH


3


)CH═CH


2


, SC(CH


3


)


2


CH═CH


2


, SCH


2


C(Cl)CH


2


, SCH(CH


3


)C(Cl)═CH


2


, SCH


2


C(CH


3


)═CH


2


, SCH


2


C≡CH, SCH(CH


3


)C≡CH, SC(CH


3


)


2


C≡CH, SCH


2


-c-Pr, SCH


2


-c-Pen, SCH


2


-c-Hex, SCH


2


CN, SCH(CH


3


)CN, SCOMe, SCOEt, SCOPr, SCO-i-Pr, SCOCF


3


, SCOCF


2


H, SCH


2


COOH, SCH


2


COOMe, SCH


2


COOEt, SCH


2


COOPr, SCH


2


COO-i-Pr, SCH


2


COOBu, SCH


2


COO-s-Bu, SCH


2


COOPen, SCH


2


COOHex, SCH


2


COOHep, SCH


2


COO-c-Pen, SCH


2


COO-c-Hex, SCH


2


COOCH


2


CH═CH


2


, SCH


2


COOCH


2


C≡CH, SCH


2


COOPh, SCH


2


COOCH


2


Ph, SCH


2


COOCH


2


COOH, SCH


2


COOCH


2


COOMe, SCH


2


COOCH


2


COOEt, SCH


2


COOCH


2


COOPr, SCH


2


COOCH


2


COO-i-Pr, SCH


2


COOCH


2


COOBu, SCH


2


COOCH


2


COO-c-Pen, SCH


2


COOCH


2


COO-c-Hex, SCH


2


COOCH


2


COOCH


2


CH═CH


2


, SCH


2


COOCH


2


COOCH


2


C≡CH, SCH


2


COOCH(CH


3


)COOH, SCH


2


COOCH(CH


3


)COOMe, SCH


2


COOCH(CHOCOOEt, SCH


2


COOCH(CH


3


)COOPr, SCH


2


COOCH(CH


3


)COO-i-Pr, SCH


2


COOCH(CH


3


)COOBu, SCH


2


COOCH(CH


3


)COO-c-Pen, SCH


2


COOH(CH


3


)COO-c-Hex, SCH


2


COOCH(CH


3


)COOCH


2


CH═CH


2


, SCH


2


COOH(CH


3


)COOCH


2


C≡CH, SCH


2


COOC(CH


3


)


2


COOH, SCH


2


COOC(CH


3


)


2


COOMe, SCH


2


COOC(CH


3


)


2


COOEt, SCH


2


COOC(CH


3


)


2


COOPr, SCH


2


COOC(CH


3


)


2


COO-i-Pr, SCH


2


COOC(CH


3


)


2


COOBu, SCH


2


COOC(CH


3


)


2


COO-c-Pen, SCH


2


COOC(CH


3


)


2


COO-c-Hex, SCH


2


COOC(CH


3


)


2


COOCH


2


CH═CH


2


, SCH


2


COOC(CH


3


)


2


COOCH


2


C≡CH, SCH(CH


3


)COOH, SCH(CH


3


)COOMe, SCH(CH


3


)COOEt, SCH(CH


3


)COOPr, SCH(CH


3


)COO-i-Pr, SCH(CH


3


)COOBu, SCH(CH


3


)COO-s-Bu, SCH(CH


3


)COOPen, SCH(CH


3


)COOHex, SCH(CH


3


)COOHep, SCH(CH


3


)COO-c-Pen, SCH(CH


3


)COO-c-Hex, SCH(CH


3


)COOCH


2


CH═CH


2


, SCH(CH


3


)COOCH


2


C≡CH, SCH(CH


3


)COOPh, SCH(CH


3


)COOCH


2


Ph, SCH(CH


3


)COOCH


2


COOH, SCH(CH


3


)COOCH


2


COOMe, SCH(CH


3


)COOCH


2


COOEt, SCH(CH


3


)COOCH


2


COOPr, SCH(CH


3


)COOCH


2


COO-i-Pr, SCH(CH


3


)COOCH


2


COOBu, SCH(CH


3


)COOCH


2


COO-c-Pen, SCH(CH


3


)COOCH


2


COO-c-Hex, SCH(CH


3


)COOCH


2


COOCH


2


CH═CH


2


, SCH(CH


3


)COOCH


2


COOCH


2


C≡CH, SCH(CH


3


)COOCH(CH


3


)COOH, SCH(CH


3


)COOCH(CH


3


)COOMe, SCH(CH


3


)COOCH(CH


3


)COOEt, SCH(CH


3


)COOCH(CH


3


)COOPr, SCH(CH


3


)COOCH(CH


3


)COO-i-Pr, SCH(CH


3


)COOCH(CH


3


)COOBu, SCH(CH


3


)COOCH(CH


3


)COO-c-Pen, SCH(CH


3


)COOCH(CH


3


)COO-c-Hex, SCH(CH


3


)COOCH(CH


3


)COOCH


2


CH═CH


2


, SCH(CH


3


)COOCH(CH


3


)COOCH


2


C≡CH, SCH(CH


3


)COOC(CH


3


)


2


COOH, SCH(CH


3


)COOC(CH


3


)


2


COOMe, SCH(CH


3


)COOC(CH


3


)


2


COOEt, SCH(CH


3


)COOC(CH


3


)


2


COOPr, SCH(CH


3


)COOC(CH


3


)


2


COO-i-Pr, SCH(CH


3


)COOC(CH


3


)


2


COOBu, SCH(CH


3


)COOC(CH


3


)


2


COO-c-Pen, SCH(CH


3


)COOC(CH


3


)


2


COO-c-Hex, SCH(CH


3


)COOC(CH


3


)


2


COOCH


2


CH═CH


2


, SCH(CH


3


)COOC(CH


3


)


2


COOCH


2


C≡CH, SCH


2


CON(Me)


2


, SCH


2


CON(Et)


2


, SCH(CH


3


)CON(Me)


2


, SCH(CH


3


)CON(Et)


2


, NH-Me, NH-Et, NH-Pr, NH-i-Pr, NH-Bu, NH-i-Bu, NH-s-Bu, NH-Pen, NH-c-Pen, NH-Hex, NH-c-Hex, NH-Hep, NH-Oct, NHCH


2


CH═CH


2


, NHCH(CH


3


)CH═CH


2


, NHC(CH


3


)


2


CH═CH


2


, NHCH


2


C(Cl)═CH


2


, NHCH(CH


3


)C(Cl)═CH


2


, NHCH


2


C(CH


3


)═CH


2


, NHCH


2


C≡CH, NHCH(CH


3


)C≡CH, NHC(CH


3


)


2


C≡CH, NHCH


2


-c-Pr, NHCH


2


-c-Pen, NHCH


2


-c-Hex, NHCH


2


CN, NHCH(CH


3


)CN, NHCOMe, NHCOEt, NHCOPr, NHCO-i-Pr, NHCOCF


3


, NHCOCF


2


H, NHCOOMe, NHCOOEt, NHCOOPr, NHCOO-i-Pr, NHSO


2


Me, NHSO


2


Et, NHSO


2


Pr, NHSO


2


-i-Pr, NHSO


2


CH


2


Cl, NHSO


2


CF


3


, NHCH


2


COOH, NHCH


2


COOMe, NHCH


2


COOEt, NHCH


2


COOPr, NHCH


2


COO-i-Pr, NHCH


2


COOBu, NHCH


2


COO-s-Bu, NHCH


2


COOPen, NHCH


2


COOHex, NHCH


2


COOHep, NHCH


2


COO-c-Pen, NHCH


2


COO-c-Hex, NHCH


2


COOCH


2


CH═CH


2


, NHCH


2


COOCH


2


C≡CH, NHCH


2


COOPh, NHCH


2


COOCH


2


Ph, NHCH


2


COOCH


2


COOH, NHCH


2


COOCH


2


COOMe, NHCH


2


COOCH


2


COOEt, NHCH


2


COOCH


2


COOPr, NHCH


2


COOCH


2


COO-i-Pr, NHCH


2


COOCH


2


COOBu, NHCH


2


COOCH


2


COO-c-Pen, NHCH


2


COOCH


2


COO-c-Hex, NHCH


2


COOCH


2


COOCH


2


CH═CH


2


, NHCH


2


COOCH


2


COOCH


2


C≡CH, NHCH


2


COOCH(CH


3


)COOH, NHCH


2


COOCH(CH


3


)COOMe, NHCH


2


COOCH(CH


3


)COOEt, NHCH


2


COOCH(CH


3


)COOPr, NHCH


2


COOCH(CH


3


)COO-i-Pr, NHCH


2


COOCH(CH


3


)COOBu, NHCH


2


COOCH(CH


3


)COO-c-Pen, NHCH


2


COOCH(CH


3


)COO-c-Hex, NHCH


2


COOCH(CH


3


)COOCH


2


CH═CH


2


, NHCH


2


COOCH(CH


3


)COOCH


2


C≡CH, NHCH


2


COOC(CH


3


)


2


COOH, NHCH


2


COOC(CH


3


)


2


COOMe, NHCH


2


COOC(CH


3


)


2


COOEt, NHCH


2


COOC(CH


3


)


2


COOPr, NHCH


2


COOC(CH


3


)


2


COO-i-Pr, NHCH


2


COOC(CH


3


)


2


COOBu, NHCH


2


COOC(CH


3


)


2


COO-c-Pen, NHCH


2


COOC(CH


3


)


2


COO-c-Hex, NHCH


2


COOC(CH


3


)


2


COOCH


2


CH═CH


2


, NHCH


2


COOC(CH


3


)


2


COOCH


2


C≡CH, NHCH(CH


3


)COOH, NHCH(CH


3


)COOMe, NHCH(CH


3


)COOEt, NHCH(CH


3


)COOPr, NHCH(CH


3


)COO-i-Pr, NHCH(CH


3


)COOBu, NHCH(CH


3


)COO-s-Bu, NHCH(CH


3


)COOPen, NHCH(CH


3


)COOHex, NHCH(CH


3


)COOHep, NHCH(CH


3


)COO-c-Pen, NHCH(CH


3


)COO-c-Hex, NHCH(CH


3


)COOCH


2


CH═CH


2


, NHCH(CH


3


)COOCH


2


C≡CH, NHCH(CH


3


)COOPh, NHCH(CH


3


)COOCH


2


Ph, NHCH(CH


3


)COOCH


2


COOH, NHCH(CH


3


)COOCH


2


COOMe, NHCH(CH


3


)COOCH


2


COOEt, NHCH(CH


3


)COOCH


2


COOPr, NHCH(CH


3


)COOCH


2


COO-i-Pr, NHCH(CH


3


)COOCH


2


COOBu, NHCH(CH


3


)COOCH


2


COO-c-Pen, NHCH(CH


3


)COOCH


2


COO-c-Hex, NHCH(CH


3


)COOCH


2


COOCH


2


CH═CH


2


, NHCH(CH


3


)COOCH


2


COOCH


2


C≡CH, NHCH(CH


3


)COOCH(CH


3


)COOH, NHCH(CH


3


)COOCH(CH


3


)COOMe, NHCH(CH


3


)COOCH(CH


3


)COOEt, NHCH(CH


3


)COOCH(CH


3


)COOPr, NHCH(CH


3


)COOCH(CH


3


)COO-i-Pr, NHCH(CH


3


)COOCH(CH


3


)COOBu, NHCH(CH


3


)COOCH(CH


3


)COO-c-Pen, NHCH(CH


3


)COOCH(CH


3


)COO-c-Hex, NHCH(CH


3


)COOCH(CH


3


)COOCH


2


CH═CH


2


, NHCH(CH


3


)COOCH(CH


3


)COOCH


2


C≡CH, NHCH(CH


3


)COOC(CH


3


)


2


COOH, NHCH(CH


3


)COOC(CH


3


)


2


COOMe, NHCH(CH


3


)COOC(CH


3


)


2


COOEt, NHCH(CH


3


)COOC(CH


3


)


2


COOPr, NHCH(CH


3


)COOC(CH


3


)


2


COO-i-Pr, NHCH(CH


3


)COOC(CH


3


)


2


COOBu, NHCH(CH


3


)COOC(CH


3


)


2


COO-c-Pen, NHCH(CH


3


)COOC(CH


3


)


2


COO-c-Hex, NHCH(CH


3


)COOC(CH


3


)


2


COOCH


2


CH═CH


2


, NHCH(CH


3


)COOC(CH


3


)


2


COOCH


2


C≡CH, NHCH


2


CON(Me)


2


, NHCH


2


CON(Et)


2


, NHCH(CH


3


)CON(Me)


2


, NHCH(CH


3


)CON(Et)


2


, COOH, COOMe, COOEt, COOPr, COO-i-Pr, COOBu, COO-s-Bu, COOPen, COOHex, COOCH


2


Ph, COO-c-Pen, COO-c-Hex, COOCH


2


COOH, COOCH


2


COOMe, COOCH


2


COOEt, COOCH


2


COOPr, COOCH


2


COO-i-Pr, COOCH


2


COOBu, COOCH


2


COO-c-Pen, COOCH


2


COO-c-Hex, COOCH


2


COOCH


2


CH═CH


2


, COOCH


2


COOCH


2


C≡CH, COOCH(CH


3


)COOH, COOCH(CH


3


)COOMe, COOCH(CH


3


)COOEt, COOCH(CH


3


)COOPr, COOCH(CH


3


)COO-i-Pr, COOCH(CH


3


)COOBu, COOCH(CH


3


)COO-c-Pen, COOCH(CH


3


)COO-c-Hex, COOCH(CH


3


)COOCH


2


CH═CH


2


, COOCH(CH


3


)COOCH


2


C≡CH, COOC(CH


3


)


2


COOH, COOC(CH


3


)


2


COOMe, COOC(CH


3


)


2


COOEt, COOC(CH


3


)


2


COOPr, COOC(CH


3


)


2


COO-i-Pr, COOC(CH


3


)


2


COOBu, COOC(CH


3


)


2


COO-c-Pen, COOC(CH


3


)


2


COO-c-Hex, COOC(CH


3


)


2


COOCH


2


CH═CH


2


, COOC(CH


3


)


2


COOCH


2


C≡CH, CON(Et)


2


, CON(Me)


2


, CON(Et)


2


, CH


2


CH


2


COOH, CH


2


CH


2


COOMe, CH


2


CH


2


COOEt, CH


2


CH


2


COOPr, CH


2


CH


2


COO-i-Pr, CH


2


CH


2


COOBu, CH


2


CH(Cl)COOH, CH


2


CH(Cl)COOMe, CH


2


CH(Cl)COOEt, CH


2


CH(Cl)COOPr, CH


2


CH(Cl)COO-i-Pr, CH


2


CH(Cl)COOBu, CH═CHCOOH, CH═CHCOOMe, CH═CHCOOEt, CH═CHCOOPr, CH═CHCOO-i-Pr, CH═CHCOOBu, CH═C(Cl)COOH, CH═C(Cl)COOMe, CH═C(Cl)COOEt, CH═C(Cl)COOPr, CH═C(Cl)COO-i-Pr, CH═C(Cl)COOBu, C(Me)═CHCOOH, C(Me)═CHCOOMe, C(Me)═CHCOOEt, C(Me)═CHCOOPr, C(Me)═CHCOO-i-Pr, C(Me)═CHCOOBu, CH═C(Me)COOH, CH═C(Me)COOMe, CH═C(Me)COOEt, CH═C(Me)COOPr, CH═C(Me)COO-i-Pr, CH═C(Me)COOBu, CH═NOH, CH═NOMe, CH═NOEt, CH═NOPr, CH═NO-i-Pr, CH═NOBu, C(Me)═NOH, C(Me)═NOMe, C(Me)═NEt, C(Me)═NOPr, C(Me)═NO-i-Pr, C(Me)═NOBu, CH═NOCH


2


COOMe, CH═NOCH


2


COOEt, CH═NOCH


2


COOPr, CH═NOCH


2


COO-i-Pr, CH═NOCH


2


COOBu, C(Me)═NOCH


2


COOMe, C(Me)═NOCH


2


COOEt, C(Me)═NOCH


2


COOPr, C(Me)═NOCH


2


COO-i-Pr, or (Me)═NOCH


2


COOBu;




R


3


′s are selected from hydrogen, fluorine, chlorine, bromine, iodine, NO


2


, CN, O-Me, O-Et, O-Pr, O-i-Pr, O-Bu, O-i-Bu, O-s-Bu, O-Pen, O-c-Pen, O-Hex, O-c-Hex, O-Hep, O-Oct, OCH


2


COOMe, OCH


2


COOEt, OCH


2


COOPr, OCH


2


COO-i-Pr, OCH


2


COOBu, OCH


2


COO-s-Bu, OCH


2


COOPen, OCH


2


COOHex, OCH


2


COOHep, OCH


2


C(═NOMe)COOMe, OCH


2


C(═NOMe)COOEt, OCH


2


C(═NOMe)COOPr, OCH(CH


3


)COOMe, OCH(CH


3


)COOEt, OCH(CH


3


)COOPr, OCH(CH


3


)COO-i-Pr, OCH(CH


3


)COOBu, OCH(CH


3


)COO-s-Bu, OCH(CH


3


)COOPen, OCH(CH


3


)COOHex, OCH(CH


3


)COOHep, OCH(CH


3


)C(═NOMe)COOMe, OCH(CH


3


)C(═NOMe)COOEt, or OCH(CH


3


)C(═NOMe)COOPr; and




R


4


′s are selected from hydrogen, fluorine, chlorine, bromine, iodine, NO


2


, or CN.











EXAMPLES




The present invention will be further illustrated by the following Production Examples, Formulation Examples, and lest Examples; however, the present invention is not limited to these Examples. The numbers of the present compounds are those as shown in Tables 1 to 54.




Production Example 1
















To a suspension of 60.0 g of potassium carbonate in 300 ml of acetone was added 25 g of compound 1a and then added 35.7 g of ethyl bromoacetate, and the mixture was heated and stirred at the reflux-temperature of acetone for 1 hour. The reaction mixture was then cooled to room temperature and filtered to remove insoluble matter. The filtrate was concentrated to give 45.8 g of compound 1b as a crude product.




To a solution of 45.8 g of this crude product of compound 1b in 300 ml of N,N-dimethylformamide was added 30.0 g of potassium carbonate, and the mixture was heated and stirred at a temperature of 100° C. to 110° C. for 5 hours. The reaction mixture was then cooled to room temperature and poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated to give 36.5 g of compound 1c as crystals.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.44 (3H, t, J=7.09 Hz), 4.44 (2H, q, J=7.07 Hz), 4.65-5.38 (2H, br), 7.21-7.27 (1H, m), 7.44-7.57 (3H, m).




To a solution of 10.2 g of compound 1c in 50 ml of tetrahydrofaran was added 6.5 g of ethyl chloroformate and 7.3 g of N,N-diethylaniline, and the mixture was heated and stirred at the reflux temperature of tetrahydrofuran for 3 hours. The reaction mixture was then cooled to room temperature and poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated to give 13.05 g of compound 1d.




m.p.: 90.6° C.




To a suspension of 2.4 g of sodium hydride in 50 ml of N,N-dimethylformamide was added 11.0 g of ethyl 4,4,4-trifluoro-3-aminochrotonate below 10° C., and the mixture was stirred for 30 minutes. The reaction mixture was then warmed to room temperature, to which a solution of 13.0 g of compound 1d in 20 ml of N,N-dimethylformamide was added, and the reaction mixture was then warmed to 100° C. to 110° C., at which temperature the mixture was kept and stirred for 2.5 hours. The reaction mixture was then cooled to room temperature, to which 10.0 g of methyl iodide was added, and the mixture was stirred at room temperature overnight. The reaction mixture was then poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=4:1) to give 4.56 g of compound 1e.




m.p.: 107.2° C.




First, 1.0 g of compound 1e was added to 5 ml of 85% sulfuric acid, and the mixture was warmed to 110° C., heated and stirred for 5 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 0.81 g of compound 1f.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 3.59-3.60 (3H, m), 6.41 (1H, s), 7.26-7.67 (4H, m).




First, 0.7 g of compound 1f and 0.05 g of copper powder were added to 3 ml of quinoline, and the mixture was warmed to 150° C., at which temperature the mixture was kept and stirred for 1 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate 5:1) to give 0.43 g of compound 1g (the present compound 1-1).






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 3.51 (3H, m), 6.34 (1H, s), 7.21-7.54 (4H, m), 7.81 (1H, s).




Production Example 2
























To 200 ml of ethanol were added 25 g of compound 2a and 10.9 g of hydroxylamine hydrochloride, and the mixture was stirred at room temperature overnight. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 26.06 g of compound 2b.




To a solution of 26.0 g of compound 2b in 100 ml of chloroform was added 22.4 g of 1,1′-carbonyldiimidazole under ice cooling, and the mixture was stirred at room temperature for 30 minutes, then heated and stirred at the reflux temperature of chloroform for 1 hour. The reaction mixture was then concentrated, and diluted hydrochloric acid was added to the residue, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated to give 15.88 g of compound 2c.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 7.46 (1H, d, J=2.45 Hz), 7.57 (1H, d, J=2.45 Hz).




To a suspension of 16.5 g of potassium carbonate in 80 ml of acetone was added 15 g of compound 2c and then added 14.6 g of ethyl bromoacetate, and the mixture was heated and stirred at the reflux temperature of acetone for 4 hours. The reaction mixture was then cooled to room temperature and filtered to remove insoluble matter, and the filtrate was then concentrated to give compound 2d as a crude product.




To a solution of this crude product of compound 2d in 150 ml of N,N-dimethylformamide was added 50.0 g of potassium carbonate, and the mixture was heated and stirred at a temperature of 90° C. to 100° C. for 30 minutes. The reaction mixture was then cooled to room temperature and poured into water, and the deposited crystals were collected by filtration. The crystals were washed with water and dried to give 21.49 g of compound 2e.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.44 (3H, t, J=7.07 Hz), 4.45 (2H, q, J=7.07 Hz), 4.82-5.13 (2H, br), 7.44-7.45 (2H, m).




To 60 ml of toluene were added 4.0 g of compound 2e, 2.8 g of trichloromethyl chloroformate, and 1 g of activated carbon (powder), and the. mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was then filtered, and the filtrate was concentrated to give 13.0 g of compound 2f as a crude product.




In a suspension of 0.64 g of sodium hydride in 20 ml of N,N-dimethylformamide was added 3.0 g of ethyl 4,4,4-trifluoro-3-aminichrotonate below 10° C., and the mixture was stirred for 30 minutes. 1b the reaction mixture was added dropwise at −30° C. a solution of 13.0 g of this crude product of compound 2f in 30 ml of tetrahydrofuran. After completion of the dropwise addition, the reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours. To the reaction mixture was then added 3.0 g of methyl iodide, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, then and concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=4:1) to give 4.51 g of compound 2g.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.33 (3H, t, J=7.06 Hz), 3.59 (3H, m), 4.39 (2H, q, J=6.93 Hz), 6.39 (1H, s), 7.36 (1H, d, J=2.65 Hz), 7.51 (1H, d, J=2.65 Hz).




First, 4.5 g of compound 2g was added to 20 ml of 85% sulfuric acid, and the mixture was heated to 100° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 3.57 g of compound 2h.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 3.59-3.60 (3H, m), 6.40 (1H, s), 7.38 (1H, d, J=1.77 Hz), 7.54 (1H, d, J=1.77 Hz).




To 10 ml of quinoline were added 3.0 g of compound 2h and 0.07 g of copper powder, and the mixture was heated to 120° C. to 150° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 1.62 g of compound 2i (the present compound 1-2).






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 3.59-3.60 (3H, m), 6.40 (1H, s), 7.24 (1H, d, J=1.89), 7.37 (1H, d, J=1.89), 7.93 (1H, s).




Production Example 3
















To a solution of 9.77 g of acetohydroxamic acid in 150 ml of N,N-dimethylformamide was added 14.6 g of potassium t-butoxide at room temperature, and the mixture was. stirred at room temperature for 30 minutes. To the reaction mixture was added 10.5 g of compound 3a at room temperature, and the mixture was left undisturbed at room temperature for 3 days. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with n-hexane to give 6.95 g of compound 3b.




To 2 ml of propionic acid were added 500 mg of compound 3b and 567 mg of 3,4,5,6-tetrahydrophthalic anhydride, and the mixture was heated and stirred at the reflux temperature of propionic acid for 24 hours. The reaction mixture was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=5:1) to give 200 mg of compound 3c (the present compound 2-4).






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.84-1.89 (4H, m), 2.48-2.52 (4H, m), 7.31-7.40 (1H, m), 7.55-7.75 (3H, m).




Production Example 4
















To a solution of 10.4 g of ethyl thioglycolate in 20 ml of N,N-dimethylformamide were added 12.4 g of potassium carbonate and 20 ml of N,N-dimethylformamide, and the mixture was warmed to 40° C. To the reaction mixture was added 10.0 g of compound 4a, and the mixture was warmed to 85° C., at which temperature the mixture was kept and stirred for 2 hours. The reaction mixture was left undisturbed at room temperature overnight. To the reaction mixture were then added 33.7 g of potassium carbonate and 30 ml of N,N-dimethylformamide, and the mixture was heated and stirred at 100° C. to 110° C. for 4 hours. The reaction solution was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=4:1) to give 14.44 g of compound 4b.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.39 (3H, t, J=7.09 Hz), 4.36 (2H, q, J=7.11 Hz), 5.90 (2H, bs), 7.34-7.74 (4H, m).




To a solution of 4.0 g of compound 4b in 50 ml of toluene was added 3.58 g of trichloromethyl chloroformate, and the mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was concentrated to give compound 4c as a crude product.




To a suspension of 0.87 g of sodium hydride in 15 ml of N,N-dimethylformamide was added 4.0 g of ethyl 4,4,4-trifluoro-3-aminochrotonate below 10° C., and the mixture was stirred for 30 minutes. To the reaction was then added dropwise at −30° C. a solution of this crude product of compound 4c in the whole amount dissolved in 50 ml of tetrahydrofuran. After completion of the dropwise addition, the mixture was warmed to room temperature and left undisturbed overnight. To the reaction mixture was then added 3.85 g of methyl iodide, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=4:1) to give 2.36 g of compound 4b as crystals.




m.p.: 112.6° C.




To 15 ml of 85% sulfuric acid was added 2.3 g of compound 4d, and the mixture was warmed to 110° C., at which temperature the mixture was kept and stirred for 15 minutes. The reaction mixture was then poured into water, and the precipitated crystals were collected by filtration and dried to give 1.61 g of compound 4e.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 3.58 (3H, m), 6.42 (1H, s), 7.41-7.91 (4H, m).




To 12 ml of quinoline were added 1.5 g of compound 4e and 0.06 g of copper powder, and the mixture was warmed to 120° C. to 140° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=4:1) to give 1.07 g of compound 4f (the present compound 1-3).




m.p.: 156.8° C.




Production Example 5
















According to the process as described above in Production Example 2, compound 5a (the present compound 1-6) was produced from 2-hydroxy-5-nitrobenzaldehyde.




m.p.: 231.9° C. (decomposition).




To a mixed solvent of 40 ml of acetic acid and 20 ml of water was added 4.5 g of iron powder, to which suspension 4.5 g of compound 5a was added, and the mixture was heated and stirred at the reflux temperature of the solvent for 20 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and then concentrated to give 2.64 g of compound 5b (the present compound 1-7).






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.25-3.82 (2H, br), 3.58 (3H, m), 6.39 (1H, s), 6.55 (1H, d, J=2.30 Hz), 6.71 (1H, dd, J=8.76 Hz, 2.30 Hz), 7.32 (1H, d, J=8.76 Hz), 7.73 (1H, s).




To a solution of 0.8 g of compound 5b dissolved in 6 ml of pyridine was added 0.3 g of methanesulfonyl chloride at room temperature, and the mixture was stirred for 2 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, with aqueous hydrochloric acid solution, and then with water, dried over anhydrous magnesium sulfate, and then concentrated. The deposited crystals were washed with t-butyl methyl ether to give 0.55 g of compound 5c (the present compound 1-10).




m.p.: 105.3° C.




Production Example 6
















To 6 ml of methyl iodide was added 0.6 g of compound 5b, and the mixture was heated and stirred at the reflux temperature of methyl iodide for 4 hours. The reaction mixture was concentrated, and the residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.14 g of compound 6a (the present compound 1-8) and 0.065 g of compound 6b (the present compound 1-9).




Compound 6a.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 2.82 (3H, s), 3.57-3.58 (3H, m), 6.37-6.67 (3H, m), 7.33 (1H, d, J=8.85 Hz), 7.71 (1H, s).




Compound 6b.




m.p.: 166.1° C. (decomposition).




Production Example 7
















To 10 ml of acetonitrile were added 0.53 g of copper (II) chloride and 0.57 g of isobutyl nitrite, to which 3 ml of ethyl acrylate was added under ice cooling, and the mixture was stirred for 10 minutes. A solution of 1.0 g of compound 5b dissolved in 5 ml of acetonitrile was then added to the reaction mixture under ice cooling. The mixture obtained was stirred for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 0.64 g of compound 7a (the present compound 1-407).






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.18 (3H, t, J.=7.12 Hz), 3.18-3.48 (2H, m), 3.56-3.57 (3H, m), 4.10-4.20 (2H, m), 4.41 (1H, t, J=7.43 Hz), 6.39 (1H, s), 7.19-7.49 (3H, m), 7.82 (1H, s).




Production Example 8
















According to the process as described above in Production Example 2, compound 8a (the present compound 1-5) was produced from 2-hydroxy-5-methoxybenzaldehyde.




m.p.: 135.0° C.




To a solution of 0.64 g of compound 8a dissolved in 4 ml of chloroform was added 0.5 g of iodotrimethylsilane, and the mixture was kept and stirred at 40° C. to 50° C. for 10.5 hours. The mixture was then left undisturbed at room temperature for a half day, to which 0.5 g of iodotrimethylsilane was further added, and the mixture was further kept and stirred at 40° C. to 50° C. for 10.5 hours. The reaction mixture was then poured into ice water, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.37 g of compound 8b (the present compound 1-78).






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 3.58-3.59 (3H, m), 5.09 (1H, bs) 6.39 (1H, s), 6.68 (1H, d, J=2.32 Hz), 6.82 (1H, dd, J=8.83 Hz, 2.32 Hz), 7.37 (1H, d, J=8.85 Hz), 7.79 (1H, s).




To a suspension of 0.05 g of sodium hydride in 1 ml of N,N-dimethylformamide was added a solution of 0.35 g of compound 8b in 2 ml of N,N-dimethylformamide under ice cooling, and the mixture was stirred for 5 minutes. Then, 0.23 g of ethyl bromoacetate was added under ice cooling, and the mixture was stirred for 0.5 hour. The reaction mixture was poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.34 g of compound 8c (the present compound 1-127).






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.21 (3H, t, J=7.06 Hz), 1.60 (3H, d, J=6.82 Hz), 3.58-3.59 (3H, m), 4.10-4.23 (2H, m), 4.73 (1H, q, J=6.82 Hz), 6.38 (1H, s), 6.74 (1H, d, J=2.52 Hz), 6.97 (1H, dd, J=9.21 Hz, 2.80 Hz), 7.43 (1H, d, J=9.29 Hz), 7.80 (1H, s).




Production Example 9
















In a solution of 1.0 g of compound 5b dissolved in 10 ml of acetic acid was added 0.045 g of acetic anhydride, and the mixture was stirred at room temperature for 3 hours. A mixed solution of hexane:ethyl acetate=1:1 was then added, and the deposited crystals were collected by filtration and dried to give 1.16 g of compound 9a (the present compound 1-24).






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 2.10 (3H, s), 3.59 (3H, s), 6.39 (1H, s), 7.12 (1H, dd, J=8.80 Hz, 2.10 Hz), 7.29 (1H, bs), 7.44 (1H, d, J=8.82 Hz), 7.77 (1H, d, J=1.88 Hz), 7.81 (1H, s).




In a solution of 1.0 g of compound 9a dissolved in 10 ml of dimethylformamide was added 0.11 g of sodium hydride at room temperature, and the mixture was stirred for 10 minutes. Then, 0.43 g of methyl iodide was added at room temperature, and the mixture was left undisturbed for 3 days. The reaction mixture was then poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, and dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.36 g of compound 9b (the present compound 1-28).




m.p.: 207.2° C.




Production Example 10
















According to the process as described above in Production Example 2, compound 10a (the present compound 1-75) was produced from 2-hydroxy-5-bromobenzaldehyde.




m.p.: 130.0° C.




To a solution of 1.85 g of compound 10a in 10 ml of N-methylpyrrolidone was added 0.67 g of copper (I) cyanide, and the mixture was heated and stirred at 170° C. to 180° C. for 6 hours. After cooling to room temperature, the reaction mixture was poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with cold ammonia water, with water, and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.85 g of compound 10b (the present compound 1-283).




m.p.: 174.3° C. (decomposition).




After 0.65 g of compound 10b was dissolved in 85% sulfuric acid, the solution was kept and stirred at 50° C. to 60° C. for 0.5 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.45 g of compound 10c (the present compound 1-293).






1


H-NMR (300 MHz, CDCl


3


+DMSO, TMS, δ (ppm)): 3.60 (3H, s), 6.40 (1H, s), 7.58 (1H, d, J=8.76 Hz), 7.84-7.95 (3H, m).




First, 0.3 g of compound 10c was added to 10 ml of a solution of boron trifluoride methanol complex in methanol, and the mixture was heated and stirred at the reflux temperature for 7 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.22 g of compound 10d (the present compound 1-303).






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.59 (3H, m), 3.92 (3H, s), 6.40 (1H, s), 7.58 (1H, d, J=9.06 Hz), 7.89 (1H, s), 8.06-8.09 (2H, m).




Production Example 11
















To a solution of 10.45 g of compound 11a, which had been produced according to the process as described in the JP-A 58-79960 publication, in 30 ml of N-methylpyrrolidone was added 4.56 g of copper (I) cyanide, and the mixture was kept and stirred at 110° C. to 120° C. for 6 hours. After cooling to room temperature, the reaction mixture was poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with cold ammonia water, with water, and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 5.14 g of compound [11b].






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.32 (3H, t, J=7.17 Hz), 4.31 (2H, q, J=7.22 Hz), 4.89 (2H, s), 7.70 (1H, d, J=1.82 Hz), 7.80 (1H, d, J=8.57 Hz), 7.93-7.95 (1H, m).




To a solution of 5.1 g of compound 11b in 50 ml of N,N-dimethylformamide was added 3.3 g of potassium carbonate, and the mixture was kept and stirred at 100° C. for 30 minutes. The reaction mixture was then cooled to room temperature and poured into water. The deposited crystals were collected by filtration. The crystals were washed with water and dried to give 4.0 g of compound 11c.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.46 (3H, t, J=7.24 Hz), 4.47 (2H, q, J=7.08 Hz), 5.30 (2H, bs), 7.69 (1H, d, J=8.67 Hz), 8.16 (1H, dd, J=8.76 Hz, 1.77 Hz), 8.34 (1H, d, J=1.87 Hz).




To a solution of 3.8 g of compound 11c in 50 ml of toluene was added 3.3 g of trichloromethyl chloroformate, and the mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was then concentrated to give a crude product of isocyanate.




To a suspension of 0.67 g of sodium hydride in 5 ml of N,N-dimethylformamide was added a solution of 3.1 g of ethyl 4,4,4-trifluoro-3-amino-crotonate in 5 ml of N,N-dimethylformamide below 10° C., and the mixture was stirred for 30 minutes. To the reaction mixture was then added dropwise a solution of the crude product of isocyanate obtained from compound 11c in 100 ml of tetrahydrofuran at −30° C. After completion of the dropwise addition, the mixture was warmed to room temperature and then stirred for 1 hour. To the reaction mixture was then added 4.3 g of methyl iodide, and the mixture was left undisturbed at room temperature overnight. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=2:1) to give 3.80 g of compound 11d as crystals.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.37 (3H, t, J=7.30 Hz), 3.36 (3H, m), 4.42 (2H, q, J=6.14 Hz), 6.14 (1H, s), 7.61 (1H, d, J=8.78 Hz), 8.26 (1H, dd, J=8.67 Hz, 2.12 Hz), 8.55 (1H, d, J=1.79 Hz).




First, 3.5 g of compound 11d was added to 20 ml of 85% sulfuric acid, and the mixture was kept and stirred at a temperature of 110° C. to 120° C. for 20 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried. The whole amount of the crystals obtained and 0.23 g of copper powder were added to 15 ml of quinoline, and the mixture was warmed to 120° C. to 130° C., at which temperature the mixture was kept and stirred for 1 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2.5:1) to give 1.05 g of compound 11e (the present compound 1-282).






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.59-3.61 (3H, m), 6.42 (1H, s), 7.47 (1H, d, J=8.71 Hz), 8.11 (1H, s), 8.21 (1H, dd, J=8.79 Hz, 2.06 Hz), 8.48 (1H, d, J=1.85 Hz).




Production Example 12
















According to the process as described in the JP-A 58-79960 publication, 2-bromo-4-fluoro-5-nitrophenol was obtained from 4-fluorophenol and then used as the starting material to produce compound 12a (the present compound 1-431) according to the process as described above in Production Example 11.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.61-3.62 (3H, m), 6.42 (1H, s), 7.24 (1H, d, J=10.4 Hz), 8.13 (1H, s), 8.33 (1H, d, J=5.79 Hz).




To a solution of 0.6 g of compound 12a in 9 ml of N,N-dimethylformamide was added 0.12 g of sodium methylsulfide below 0° C., and the mixture was stirred for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, dried, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.24 g of compound 12b (the present compound 1-201).






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 2.50 (s, 3H), 3.62 (3H, m), 6.43 (1H, s), 7.19 (1H, s), 8.07 (1H, s), 8.49 (1H, d, J=5.79 Hz).




Production Example 13
















First, 1.0 g of compound 13a and 1.15 g of 3,4,5,6-tetrahydrophthalic anhydride were added to 15 ml of acetic acid, and the mixture was heated and stirred at the reflux temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was washed with hexane:isopropanol=1:1 (v/v) to give 1.48 g of compound 13b (the present compound 2-2001).






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.75-1.95 (4H, m), 2.35-2.55 (4H, m), 6.64 (1H, m), 7.01-7.15 (4H, m), 7.63 (1H, d, J=7.0 Hz).




Production Example 14
















First, 0.2 g of compound 13a and 0.4 g of ethyl 3-{[1-(dimethylamino)-methylidene]amino}-4,4,4-trifluoro-2-butenoate were added to 5 ml of acetic acid, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic, layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.05 g of compound 14a (the present compound 3-2001).






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 6.74 (1H, d, J=3.5 Hz), 7.00-7.06 (2H, m), 7.10 (1H, d, J=3.5 Hz), 7.21-7.32 (2H, m), 7.68 (1H, dd, J=1.8 Hz, 6.7 Hz), 8.40 (1H, s).




Production Example 15
















To a solution of 1.5 g of compound 15a in 15 ml of acetic acid was added 1.9 g of 3,4,5,6-tetrahydrophthalic anhydride, and the mixture was heated at reflux for 6 hours. After cooling to room temperature, the reaction mixture was poured into ice water, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 3.0 g of compound 15b (the present compound 2-2004).




m.p.: 184.5° C.




Production Example 16
















First, 25 g of compound 16a was added to 40 ml of thionyl chloride, and the mixture was heated and stirred at the reflux temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, to which residue was added 100 ml of ethanol. To the reaction mixture was then added dropwise 14 ml of pyridine under ice cooling, and the mixture was stirred at room temperature for 2 days and then left undisturbed for a half day. The reaction mixture was then concentrated, to which diluted hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic, layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated to give 27 g of compound 16b as a crude product.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.42 (3H, t, J=7.2 Hz), 2.66 (3H, s), 4.42 (2H, q, J=7.2 Hz), 7.43 (1H, d,.J=8.0 Hz), 8.15 (1H, dd, J=1.7 Hz, 8.0 Hz), 8.60 (1H, d, J=1.7 Hz).




First, 5.4 g of iron powder was added to a mixed solvent of 20 ml of acetic acid and 150 ml of water, and the mixture was heated to 70° C., to which a solution of 5.0 g of compound 16b in 20 ml of ethyl acetate was added dropwise. After completion of the dropwise addition, the mixture was left cooling to room temperature and stirred for 2 hours. Water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate, and then concentrated to give 3.8 g of compound 16c as a crude product.




m.p.: 112.6° C.




To a solution of 1.0 g of compound 16c in 50 ml of acetic acid was added dropwise a solution of 0.42 g of sodium nitrite in 5 ml of water at 10° C. After completion of the dropwise addition, the mixture was left undisturbed at room temperature for a half day. Water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.5 g of compound 16d.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.44 (3H, t, J=7.1 Hz), 4.44 (2H, q, J=7.1 Hz), 7.78-7.89 (2H1, m), 8.16 (1H, d, J=1.1 Hz), 8.29 (1H, q, J=1.1 Hz).




To a solution of 1.0 g of compound 16d in 10 ml of N,N-dimethylformamide was added 0.2 g of sodium hydride at room temperature. After the gas evolution from the reaction mixture ceased, 1.0 g of o-(2,4-dinitrophenyl)hydroxylamine was added, and the mixture was stirred. After left undisturbed for 2 days, water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.36 g of compound 16e.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.42 (3H, t, J=7.2 Hz), 4.41 (2H, q, J=7.2 Hz), 5.45 (2H, bs), 7.61-7.78 (2H, m), 7.86 (1H, s), 8.28 (1H, d, J=0.8 Hz).




First, 0.15 g of compound 16e and 0.12 g of 3,4,5,6-tetrahydrophthalic anhydride were dissolved in 10 ml of acetic acid, and the solution was heated and stirred at the reflux temperature for 1 hour. After the reaction mixture was left cooling to room temperature, water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 0.09 g of compound 16f (the present compound 2-2011).






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.42 (3H, t, J=7.2 Hz), 1.89 (4H, m), 2.50 (4H, m), 4.42 (2H, q, J=7.2 Hz), 7.79-7.84 (1H, m), 7.91-7.96 (1H, m), 8.03 (1H, m), 8.19 (1H, d, J=1.1 Hz).




Production Example 17
















First, 300 mg of compound 16e and 230 mg of phenyl chloroformate were dissolved in 10 ml of tetrahydrofuran, to which 120 mg of pyridine was added at room temperature. After stirring at room temperature for 1 hour, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 500 mg of compound 17a.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.45 (3H, t, J=7.1 Hz), 4.45 (2H, q, J=7.1 Hz), 7.15-7.42 (5H, m), 7.76-7.80 (1H, m), 7.89-7.94 (1H, m), 8.09 (1H, s), 8.27 (1H, s).




To a mixture of 280 mg of ethyl 4,4,4-trifluoro-3-aminochrotonate and 5 ml of N,N-dimethylformamide was added 60 mg of sodium hydride at room temperature, and the mixture was stirred for 10 minutes. To the reaction solution was added dropwise a solution of 500 mg of compound 17a in 6 ml of N,N-dimethylformamide. The mixture was stirred at 80° C. for 2 hours and then left cooling to room temperature, to which 500 mg of iodomethane was added. After stirring at room temperature for 4 hours, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=5:2) to give 100 mg of compound 17b (the present compound 1-2068).






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.41 (3H, t, J=7.1 Hz), 3.59 (3H, m), 4.41 (2H, q, J=7.1 Hz), 6.44 (1H, s), 7.84 (1H, d, J=9.1 Hz), 7.93-7.97 (2H, m), 8.24 (1H, d, J=0.8 Hz).




Production Example 18
















To a solution of 2.0 g of compound 3b and 1.2 g of pyridine in 10 ml of tetrahydrofuran was added dropwise a solution of 1.6 g of ClCO


2


Et in 3ml of tetrahydrofuran at 0° C. to 10° C. After stirring at room temperature for 1 hour, diluted hydrochloric acid was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was concentrated, and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 2.7 g of compound 18a.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.37 (3H, t, J=7.2 Hz), 4.33 (2H, q, J=7.2 Hz), 7.26-7.34 (2H, m), 7.48-7.58 (2H, m), 8.17 (1H, d, J=4.1 Hz).




To 15 ml of N,N-dimethylformamide was added 0.5 g of sodium hydride, to which 2.4 g of H


2


N(CF


3


)C═CHCO


2


Et was added dropwise under ice cooling. After stirring at room temperature for 30 minutes, a solution of compound 18a dissolved in 5 ml of N,N-dimethylformamide was added dropwise thereto. After heating at 100° C. for 4 hours and at 120° C. for 2 hours, the reaction mixture was cooled to room temperature. Then, 2.0 g of iodomethane was added, and the mixture was left standing overnight, to which diluted hydrochloric acid was added. The mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 2.2 g of compound 18b (the present compound 1-875).




m.p.: 159.1° C.




Production Example 19
















First, 1.3 g of potassium tert-butoxide and 0.9 g of acetohydroxamic acid were added to 25 ml of N,N-dimethylformamide, and the mixture was stirred at room temperature for 30 minutes. A solution of 1.5 g of compound 19a dissolved in 5 ml of N,N-dimethylformamide was added dropwise thereto, and the mixture was then left standing at room temperature overnight. To the reaction mixture was added aqueous sodium chloride solution, which was extracted with ethyl acetate. The organic layer was dried with magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.8 g of compound 19b.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 4.38-4.64 (1H, br), 7.20-7.27 (2H, m), 7.43-7.47 (2H, m).




To 50 ml of toluene were added 2.1 g of compound 19b (produced in the same manner as described above) and 2.5 g of trichloromethyl chloroformate, and the mixture was heated at reflux for 2 hours. The reaction mixture was concentrated to give 2.5 g of compound 19c as a crude product.




To a suspension of 0.6 g of sodium hydride in 30 ml of N,N-dimethylformamide was added 2.7 g of ethyl 4,4,4-trifluoro-3-aminochrotonate at room temperature, and the mixture was stirred for 30 minutes. To the reaction mixture was then added dropwise a solution of the whole amount of the crude product of compound 19c dissolved in 50 ml of tetrahydrofuran at 0° C. After completion of the dropwise addition, the mixture was warmed to room temperature and stirred for 3 hours, to which 2.0 g of methyl iodide was added, and the mixture was left standing overnight. The reaction mixture was then poured into diluted hydrochloric acid, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 80 mg of compound 19d (the present compound 1-877).






1


H-NMR (250 MHz, CDCl


3


, TMS,. δ (ppm)): 3.57 (3H, q, J=1.2 Hz), 6.41 (1H, s), 7.36 (1H, dd, J=1.6 Hz, 8.5 Hz), 7.45 (1H, d, J=8.5 Hz), 7.71 (1H, d, J=1.6 Hz).




Production Example 20
















To a mixed solution of 190.0 g of compound 20a, 122.9 g of methyl chloroformate, and 150 ml of water was added dropwise aqueous sodium hydroxide solution (50 g of NaOH and 100 ml of H


2


O) below 10° C. After completion of the dropwise addition, the mixture was stirred for 2 hours. The crystals obtained were then collected by filtration, washed with a solution (isopropyl alcohol:water=1:1), and dried to give 160.5 g of compound 20b.




Then, 160.0 g of compound 20b was dissolved in 250 ml of concentrated sulfuric acid, to which a mixed acid (42.5 g of fuming nitric acid and 30 ml of concentrated sulfuric acid) was added dropwise below 5° C. After completion of the dropwise addition, the mixture was stirred for 2 hours. The reaction mixture was poured into ice water, and the deposited crystals were collected by filtration, washed with water, and dried to give 186.5 g of compound 20c.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.98 (3H, s), 7.63 (1H, d, J=9.60 Hz), 8.03 (1H, d, J=6.83 Hz).




To 300 ml of water and 300 ml of ethanol was suspended 186.0 g of compound 20c, to which aqueous sodium hydroxide solution (60 g of NaOH and 120 ml of H


2


O) was added dropwise at room temperature. After completion of the dropwise addition, the mixture was stirred for 1 hour and then concentrated to remove the ethanol. The residue obtained was made acidic by the addition of concentrated hydrochloric acid under ice cooling, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated to give 141.1 g of compound 20d.




According to the process as described in Production Example 2, compound 20e was produced from compound 20d.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.32 (3H, t, J=7.11 Hz), 4.30 (211, q, J=7.14 Hz), 4.77 (2H, s), 7.51 (1H, d, J=6.28 Hz), 7.58 (1H, d, J=9.81 Hz).




According to the process as described in Production Example 11, compound 20f was produced from compound 20e.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.33 (3H, t, J=7.12 Hz), 4.30 (2H, q, J=7.12 Hz), 4.86 (2H, s), 7.52 (1H, d, J=5.66 Hz), 7.59 (1H, d, J=9.39 Hz).




First, 30 g of compound 20f was dissolved in 30 ml of N,N-dimethylformamide, to which 18.4 g of sodium acetate and 3 ml of water were added, and the mixture was kept and stirred at a temperature of 80° C. to 90° C. for 9 hours. After cooling to room temperature, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 13.6 g of compound 20 g.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm): 1.32 (3H, t, J=7.08 Hz), 4.29 (2H, q, J=7.08 Hz), 4.79 (2H, s), 7.48 (1H, s), 7.56 (1H, s).




First, 13 g of compound 20 g was dissolved in 40 ml of N,N-dimethylformamide, to which 7.3 g of potassium carbonate was added at room temperature. Then, 6.2 g of dimethylsulfuric acid was added at 30° C. to 40° C. thereto, and the mixture was stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over magnesium sulfate, and then concentrated. The crystals obtained were washed with a solution (t-butyl methyl ether:hexane=1:2) to give 10.7 g of compound 20h.






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.31 (3H, t, J=7.16 Hz), 4.00 (3H, s), 4.29 (2H, q, J=7.16 Hz), 4.78 (2H, s), 7.32 (1H, s), 7.34 (1H, s).




According to the process as described in Production Example 11, compound 20i was produced from compound 20h.




According to the process as described in Production Example 11, compound 20j (the present compound 1-86) was produced from compound 20i.






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.61 (3H, m), 3.95 (3H, s), 6.42 (1H, s), 6.89 (1H, s), 8.00 (1H, s), 8.09 (1H, s).




Examples of the present compounds are shown below together with their compound numbers.




Compounds of the general formula:












TABLE 1










































Compound




R


2






R


3






R


4






A




Y









1-1 




H




H




H




CH




O






1-2 




Cl




H




Cl




CH




O






1-3 




H




H




H




CH




S






1-4 




Cl




H




H




CH




O






1-5 




OCH


3






H




H




CH




O






1-6 




NO


2






H




H




CH




O






1-7 




NH


2






H




H




CH




O






1-8 




NHCH


3






H




H




CH




O






1-9 




N(CH


3


)


2






H




H




CH




O






1-10




NHSO


2


CH


3






H




H




CH




O






1-11




NHCH(CH


3


)CO


2


Et




H




H




CH




O






1-12




NHCH(CH


3


)CO


2


Et




H




Cl




CH




O






1-13




N(CH


3


)CH(CH


3


)CO


2


Et




H




Cl




CH




O






1-14




N(CH


3


)SO


2


CH


3






H




Cl




CH




O






1-15




NHSO


2


CH


3






H




Cl




CH




O






1-16




NHCH(CH


3


)CO


2


Et




Cl




H




CH




O






1-17




N(CH


3


)CH(CH


3


)CO


2


Et




Cl




H




CH




O



























TABLE 2









Compound




R


2






R


3






R


4






A




Y











1-18




N(CH


3


SO


2


CH


3






Cl




H




CH




O






1-19




NHSO


2


CH


3






Cl




H




CH




O






1-20




NO


2






H




Cl




CH




O






1-21




NH


2






H




Cl




CH




O






1-22




NO


2






Cl




H




CH




O






1-23




NH


2






Cl




H




CH




O






1-24




NHCOCH


3






H




H




CH




O






1-25




NHCOCF


3






H




H




CH




O






1-26




NHSO


2


Et




H




H




CH




O






1-27




NHSO


2


CH


2


Cl




H




H




CH




O






1-28




N(CH


3


)COCH


3






H




H




CH




O






1-29




N(CH


3


)COCF


3






H




H




CH




O






1-30




N(CH


3


)SO


2


Et




H




H




CH




O






1-31




CO


2


C(CH


3


)


2


CO


2


Et




H




H




CH




O






1-32




N(CH


3


)SO


2


CH


2


Cl




H




H




CH




O






1-33




NHCOCH


3






H




Cl




CH




O






1-34




NHCOCF


3






H




Cl




CH




O






1-35




NHSO


2


Et




H




Cl




CH




O






1-36




NHSO


2


CH


2


Cl




H




Cl




CH




O






1-37




N(CH


3


)COCH


3






Cl




H




CH




O






1-38




N(CH


3


)COCF


3






Cl




H




CH




O






1-39




N(CH


3


)SO


2


Et




Cl




H




CH




O






1-40




N(CH


3


)SO


2


CH


2


Cl




Cl




H




CH




O






1-42




NHCH


2


CO


2


Me




H




H




CH




O






1-43




NHCH


2


CO


2


Et




H




H




CH




O



























TABLE 3









Compound




R


2






R


3






R


4






A




Y











1-44




NHCH(CH


3


)COOH




H




H




CH




O






1-45




NHCH(CH


3


)CONH


2






H




H




CH




O






1-46




NHCH(CH


3


)CONHCH


3






H




H




CH




O






1-47




NHCH


2


CO


2


Me




H




Cl




CH




O






1-48




NHCH


2


CO


2


Et




H




Cl




CH




O






1-49




NHCH(CH


3


)COOH




H




Cl




CH




O






1-50




NHCH(CH


3


)CONH


2






H




Cl




CH




O






1-51




NHCH(CH


3


)CONHCH


3






H




Cl




CH




O






1-52




NHCH


2


CO


2


Me




Cl




H




CH




O






1-53




NHCH


2


CO


2


Et




Cl




H




CH




O






1-54




NHCH(CH


3


)COOH




Cl




H




CH




O






1-55




NHCH(CH


3


)CONH


2






Cl




H




CH




O






1-56




NHCH(CH


3


)CONHCH


3






Cl




H




CH




O






1-57




NHCH


2


CH


2


CH


3






H




H




CH




O






1-58




NHCH


2


CH═CH


2






H




H




CH




O






1-59




NHCH


2


C≡CH




H




H




CH




O






1-60




N(CH


3


)CH


2


CH


2


CH


3






H




H




CH




O






1-61




N(CH


3


)CH


2


CH═CH


2






H




H




CH




O






1-62




N(CH


3


)CH


2


C≡CH




H




H




CH




O






1-63




NHCH


2


CH


2


CH


3






H




Cl




CH




O






1-64




NHCH


2


CH═CH


2






H




Cl




CH




O






1-65




NHCH


2


C≡CH




H




Cl




CH




O






1-66




N(CH


3


)CH


2


CH


2


CH


3






H




Cl




CH




O






1-67




N(CH


3


)CH


2


CH═CH


2






H




Cl




CH




O






1-68




N(CH


3


)CH


2


C≡CH




H




Cl




CH




O



























TABLE 4









Compound




R


2






R


3






R


4






A




Y











1-69




NHCH


2


CH


2


CH


3






Cl




H




CH




O






1-70




NHCH


2


CH═CH


2






Cl




H




CH




O






1-71




NHCH


2


C≡CH




Cl




H




CH




O






1-72




N(CH


3


)CH


2


CH


2


CH


3






Cl




H




CH




O






1-73




N(CH


3


)CH


2


CH═CH


2






Cl




H




CH




O






1-74




N(CH


3


)CH


2


C≡CH




Cl




H




CH




O






1-75




Br




H




H




CH




O






1-76




Br




H




Cl




CH




O






l-77




Br




Cl




H




CH




O






1-78




OH




H




H




CH




O






1-79




OH




H




Cl




CH




O






1-80




OH




Cl




H




CH




O






1-81




OH




H




NO


2






CH




O






1-82




OH




NO


2






H




CH




O






1-83




OCH


3






H




Cl




CH




O






1-84




OCH


3






Cl




H




CH




O






1-85




OCH


3






H




NO


2






CH




O






1-86




OCH


3






NO


2






H




CH




O






1-87




OCH(CH


3


)CH


3






H




H




CH




O






1-88




OCH(CH


3


)CH


3






H




Cl




CH




O






1-89




OCH(CH


3


)CH


3






Cl




H




CH




O






1-90




OCH(CH


3


)CH


3






H




NO


2






CH




O






1-91




OCH(CH


3


)CH


3






NO


2






H




CH




O






1-92




OCH


2


CH═CH


2






H




H




CH




O






1-93




OCH


2


CH═CH


2






H




Cl




CH




O



























TABLE 5









Compound




R


2






R


3






R


4






A




Y




























1-94




OCH


2


CH═CH


2






Cl




H




CH




O






1-95




OCH


2


CH═CH


2






H




NO


2






CH




O






1-96




OCH


2


CH═CH


2






NO


2






H




CH




O






1-97




OCH(CH


3


)CH═CH


2






H




H




CH




O






1-98




OCH(CH


3


)CH═CH


2






H




Cl




CH




O






1-99




OCH(CH


3


)CH═CH


2






Cl




H




CH




O






1-100




OCH(CH


3


)CH═CH


2






H




NO


2






CH




O






1-101




OCH(CH


3


)CH═CH


2






NO


2






H




CH




O






1-102




OCH


2


C(Cl)═CH


2






H




H




CH




O






1-103




OCH


2


C(Cl)═CH


2






H




Cl




CH




O






1-104




OCH


2


C(Cl)═CH


2






Cl




H




CH




O






1-105




OCH


2


C(Cl)═CH


2






H




NO


2






CH




O






1-106




OCH


2


C(Cl)═CH


2






NO


2






H




CH




O






1-107




OCH


2


C≡CH




H




H




CH




O






1-108




OCH


2


C≡CH




H




Cl




CH




O






1-109




OCH


2


C≡CH




Cl




H




CH




O






1-110




OCH


2


C≡CH




H




NO


2






CH




O






1-111




OCH


2


C≡CH




NO


2






H




CH




O






1-112




OCH(CH


3


)C≡CH




H




H




CH




O






1-113




OCH(CH


3


)C≡CH




H




Cl




CH




O






1-114




OCH(CH


3


)C≡CH




Cl




H




CH




O






1-115




OCH(CH


3


)C≡CH




H




NO


2






CH




O






1-116




OCH(CH


3


)C≡CH




NO


2






H




CH




O






1-117




OCH(CH


3


)COOH




H




H




CH




O






1-118




OCH(CH


3


)COOH




H




Cl




CH




O



























TABLE 6









Compound




R


2






R


3






R


4






A




Y











1-119




OCH(CH


3


)COOH




Cl




H




CH




O






1-120




OCH(CH


3


)COOH




H




NO


2






CH




O






1-121




OCH(CH


3


)COOH




NO


2






H




CH




O






1-122




OCH(CH


3


)COOMe




H




H




CH




O






1-123




OCH(CH


3


)COOMe




H




Cl




CH




O






1-124




OCH(CH


3


)COOMe




Cl




H




CH




O






1-125




OCH(CH


3


)COOMe




H




NO


2






CH




O






1-126




OCH(CH


3


)COOMe




NO


2






H




CH




O






1-127




OCH(CH


3


)COOEt




H




H




CH




O






1-128




OCH(CH


3


)COOEt




H




Cl




CH




O






1-129




OCH(CH


3


)COOEt




Cl




H




CH




O






1-130




OCH(CH


3


)COOEt




H




NO


2






CH




O






1-131




OCH(CH


3


)COOEt




NO


2






H




CH




O






1-132




OCH(CH


3


)COOPr




H




H




CH




O






1-133




OCH(CH


3


)COOPr




H




Cl




CH




O






1-134




OCH(CH


3


)COOPr




Cl




H




CH




O






1-135




OCH(CH


3


)COOPr




H




NO


2






CH




O






1-136




OCH(CH


3


)COOPr




NO


2






H




CH




O






1-137




OCH(CH


3


)COO-i-Pr




H




H




CH




O






1-138




OCH(CH


3


)COO-i-Pr




H




Cl




CH




O






1-139




OCH(CH


3


)COO-i-Pr




Cl




H




CH




O






1-140




OCH(CH


3


)COO-i-Pr




H




NO


2






CH




O






1-141




OCH(CH


3


)COO-i-Pr




NO


2






H




CH




O






1-142




OCH(CH


3


)COOBu




H




H




CH




O






1-143




OCH(CH


3


)COOBu




H




Cl




CH




O



























TABLE 7









Compound




R


2






R


3






R


4






A




Y











1-144




OCH(CH


3


)COOBu




Cl




H




CH




O






1-145




OCH(CH


3


)COOBu




H




NO


2






CH




O






1-146




OCH(CH


3


)COOBu




NO


2






H




CH




O






1-147




OCH(CH


3


)COOPen




H




H




CH




O






1-148




OCH(CH


3


)COOPen




H




Cl




CH




O






1-149




OCH(CH


3


)COOPen




Cl




H




CH




O






1-150




OCH(CH


3


)COOPen




H




NO


2






CH




O






1-151




OCH(CH


3


)COOPen




NO


2






H




CH




O






1-152




OCH(CH


3


)COO-c-Pen




H




H




CH




O






1-153




OCH(CH


3


)COO-c-Pen




H




Cl




CH




O






1-154




OCH(CH


3


)COO-c-Pen




Cl




H




CH




O






1-155




OCH(CH


3


)COO-c-Pen




H




NO


2






CH




O






1-156




OCH(CH


3


)COO-c-Pen




NO


2






H




CH




O






1-157




OCH(CH


3


)COOHex




H




H




CH




O






1-158




OCH(CH


3


)COOHex




H




Cl




CH




O






1-159




OCH(CH


3


)COOHex




Cl




H




CH




O






1-160




OCH(CH


3


)COOHex




H




NO


2






CH




O






1-161




OCH(CH


3


)COOHex




NO


2






H




CH




O






1-162




OCH(CH


3


)COO-c-Hex




H




H




CH




O






1-163




OCH(CH


3


)COO-c-Hex




H




Cl




CH




O






1-164




OCH(CH


3


)COO-c-Hex




Cl




H




CH




O






1-165




OCH(CH


3


)COO-c-Hex




H




NO


2






CH




O






1-166




OCH(CH


3


)COO-c-Hex




NO


2






H




CH




O






1-167




OCH(CH


3


)CO


2


CH


2


CO


2


H




H




H




CH




O






1-168




OCH(CH


3


)CO


2


CH


2


CO


2


H




H




Cl




CH




O



























TABLE 8









Com-











pound




R


2






R


3






R


4






A




Y




























1-169




OCH(CH


3


)CO


2


CH


2


CO


2


H




Cl




H




CH




O






1-170




OCH(CH


3


)CO


2


CH


2


CO


2


H




H




NO


2






CH




O






1-171




OCH(CH


3


)CO


2


CH


2


CO


2


H




NO


2






H




CH




O






1-172




OCH(CH


3


)CO


2


CH


2


CO


2


Me




H




H




CH




O






1-173




OCH(CH


3


)CO


2


CH


2


CO


2


Me




H




Cl




CH




O






1-174




OCH(CH


3


)CO


2


CH


2


CO


2


Me




Cl




H




CH




O






1-175




OCH(CH


3


)CO


2


CH


2


CO


2


Me




H




NO


2






CH




O






1-176




OCH(CH


3


)CO


2


CH


2


CO


2


Me




NO


2






H




CH




O






1-177




OCH(CH


3


)CO


2


CH


2


CO


2


Et




H




H




CH




O






1-178




OCH(CH


3


)CO


2


CH


2


CO


2


Et




H




Cl




CH




O






1-179




OCH(CH


3


)CO


2


CH


2


CO


2


Et




Cl




H




CH




O






1-180




OCH(CH


3


)CO


2


CH


2


CO


2


Et




H




NO


2






CH




O






1-181




OCH(CH


3


)CO


2


CH


2


CO


2


Et




NO


2






H




CH




O






1-182




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




H




CH




O






1-183




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




Cl




CH




O






1-184




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




Cl




H




CH




O






1-185




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




NO


2






CH




O






1-186




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




NO


2






H




CH




O






1-187




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




H




CH




O






1-188




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




Cl




CH




O






1-189




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




Cl




H




CH




O






1-190




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




NO


2






CH




O






1-191




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




NO


2






H




CH




O






1-192




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




H




CH




O






1-193




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




Cl




CH




O



























TABLE 9









Com-











pound




R


2






R


3






R


4






A




Y




























1-194




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




Cl




H




CH




O






1-195




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




NO


2






CH




O






1-196




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




NO


2






H




CH




O






1-197




SCH


3






H




H




CH




O






1-198




SCH


3






H




Cl




CH




O






1-199




SCH


3






Cl




H




CH




O






1-200




SCH


3






H




NO


2






CH




O






1-201




SCH


3






NO


2






H




CH




O






1-202




SCH(CH


3


)CH


3






H




H




CH




O






1-203




SCH(CH


3


)CH


3






H




Cl




CH




O






1-204




SCH(CH


3


)CH


3






Cl




H




CH




O






1-205




SCH(CH


3


)CH


3






H




NO


2






CH




O






1-206




SCH(CH


3


)CH


3






NO


2






H




CH




O






1-207




SCHCH═CH


2






H




H




CH




O






1-208




SCHCH═CH


2






H




Cl




CH




O






1-209




SCHCH═CH


2






Cl




H




CH




O






1-210




SCHCH═CH


2






H




NO


2






CH




O






1-211




SCHCH═CH


2






NO


2






H




CH




O






1-212




SCHC≡CH




H




H




CH




O






1-213




SCHC≡CH




H




Cl




CH




O






1-214




SCHC≡CH




Cl




H




CH




O






1-215




SCHC≡CH




H




NO


2






CH




O






1-216




SCHC≡CH




NO


2






H




CH




O






1-217




SCH


2


COOH




H




H




CH




O






1-218




SCH


2


COOH




H




Cl




CH




O



























TABLE 10









Compound




R


2






R


3






R


4






A




Y











1-219




SCH


2


COOH




Cl




H




CH




O






1-220




SCH


2


COOH




H




NO


2






CH




O






1-221




SCH


2


COOH




NO


2






H




CH




O






1-222




SCH


2


COOMe




H




H




CH




O






1-223




SCH


2


COOMe




H




Cl




CH




O






1-224




SCH


2


COOMe




Cl




H




CH




O






1-225




SCH


2


COOMe




H




NO


2






CH




O






1-226




SCH


2


COOMe




NO


2






H




CH




O






1-227




SCH


2


COOEt




H




H




CH




O






1-228




SCH


2


COOEt




H




Cl




CH




O






1-229




SCH


2


COOEt




Cl




H




CH




O






1-230




SCH


2


COOEt




H




NO


2






CH




O






1-231




SCH


2


COOEt




NO


2






H




CH




O






1-232




SCH(CH


3


)COOH




H




H




CH




O






1-233




SCH(CH


3


)COOH




H




Cl




CH




O






1-234




SCH(CH


3


)COOH




Cl




H




CH




O






1-235




SCH(CH


3


)COOH




H




NO


2






CH




O






1-236




SCH(CH


3


)COOH




NO


2






H




CH




O






1-237




SCH(CH


3


)COOMe




H




H




CH




O






1-238




SCH(CH


3


)COOMe




H




Cl




CH




O






1-239




SCH(CH


3


)COOMe




Cl




H




CH




O






1-240




SCH(CH


3


)COOMe




H




NO


2






CH




O






1-241




SCH(CH


3


)COOMe




NO


2






H




CH




O






1-242




SCH(CH


3


)COOEt




H




H




CH




O






1-243




SCH(CH


3


)COOEt




H




Cl




CH




O



























TABLE 11









Com-











pound




R


2






R


3






R


4






A




Y




























1-244




SCH(CH


3


)COOEt




Cl




H




CH




O






1-245




SCH(CH


3


)COOEt




H




NO


2






CH




O






1-246




SCH(CH


3


)COOEt




NO


2






H




CH




O






1-247




SCH(CH


3


)COO-i-Pr




H




H




CH




O






1-248




SCH(CH


3


)COO-i-Pr




H




Cl




CH




O






1-249




SCH(CH


3


)COO-i-Pr




Cl




H




CH




O






1-250




SCH(CH


3


)COO-i-Pr




H




NO


2






CH




O






1-251




SCH(CH


3


)COO-i-Pr




NO


2






H




CH




O






1-252




SCH(CH


3


)CO


2


CH


2


CO


2


H




H




H




CH




O






1-253




SCH(CH


3


)CO


2


CH


2


CO


2


H




H




Cl




CH




O






1-254




SCH(CH


3


)CO


2


CH


2


CO


2


H




Cl




H




CH




O






1-255




SCH(CH


3


)CO


2


CH


2


CO


2


H




H




NO


2






CH




O






1-256




SCH(CH


3


)CO


2


CH


2


CO


2


H




NO


2






H




CH




O






1-257




SCH(CH


3


)CO


2


CH


2


CO


2


Me




H




H




CH




O






1-258




SCH(CH


3


)CO


2


CH


2


CO


2


Me




H




Cl




CH




O






1-259




SCH(CH


3


)CO


2


CH


2


CO


2


Me




Cl




H




CH




O






1-260




SCH(CH


3


)CO


2


CH


2


CO


2


Me




H




NO


2






CH




O






1-261




SCH(CH


3


)CO


2


CH


2


CO


2


Me




NO


2






H




CH




O






1-262




SCH(CH


3


)CO


2


CH


2


CO


2


Et




H




H




CH




O






1-263




SCH(CH


3


)CO


2


CH


2


CO


2


Et




H




Cl




CH




O






1-264




SCH(CH


3


)CO


2


CH


2


CO


2


Et




Cl




H




CH




O






1-265




SCH(CH


3


)CO


2


CH


2


CO


2


Et




H




NO


2






CH




O






1-266




SCH(CH


3


)CO


2


CH


2


CO


2


Et




NO


2






H




CH




O






1-267




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




H




CH




O






1-268




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




Cl




CH




O



























TABLE 12









Com-











pound




R


2






R


3






R


4






A




Y











1-269




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




Cl




H




CH




O






1-270




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




NO


2






CH




O






1-271




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




NO


2






H




CH




O






1-272




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




H




CH




O






1-273




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




Cl




CH




O






1-274




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




Cl




H




CH




O






1-275




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




NO


2






CH




O






1-276




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




NO


2






H




CH




O






1-277




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




H




CH




O






1-278




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




Cl




CH




O






1-279




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




Cl




H




CH




O






1-280




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




NO


2






CH




O






1-281




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




NO


2






H




CH




O






1-282




H




NO


2






H




CH




O






1-283




C≡N




H




H




CH




O






1-284




C≡N




H




Cl




CH




O






1-285




C≡N




Cl




H




CH




O






1-286




C≡N




H




NO


2






CH




O






1-287




C≡N




NO


2






H




CH




O






1-288




C(═O)H




H




H




CH




O






1-289




C(═O)H




H




Cl




CH




O






1-290




C(═O)H




Cl




H




CH




O






1-291




C(═O)H




H




NO


2






CH




O






1-292




C(═O)H




NO


2






H




CH




O






1-293




C(═O)NH


2






H




H




CH




O



























TABLE 13









Compound




R


2






R


3






R


4






A




Y











1-294




C(═O)NH


2






H




Cl




CH




O






1-295




C(═O)NH


2






Cl




H




CH




O






1-296




C(═O)NH


2






H




NO


2






CH




O






1-297




C(═O)NH


2






NO


2






H




CH




O






1-298




CO


2


H




H




H




CH




O






1-299




CO


2


H




H




Cl




CH




O






1-300




CO


2


H




Cl




H




CH




O






1-301




CO


2


H




H




NO


2






CH




O






1-302




CO


2


H




NO


2






H




CH




O






1-303




CO


2


Me




H




H




CH




O






1-304




CO


2


Me




H




Cl




CH




O






1-305




CO


2


Me




Cl




H




CH




O






1-306




CO


2


Me




H




NO


2






CH




O






1-307




CO


2


Me




NO


2






H




CH




O






i-308




CO


2


Et




H




H




CH




O






1-309




CO


2


Et




H




Cl




CH




O






1-310




CO


2


Et




Cl




H




CH




O






1-311




CO


2


Et




H




NO


2






CH




O






1-312




CO


2


Et




NO


2






H




CH




O






1-313




CO


2


CH


2


CO


2


H




H




H




CH




O






1-314




CO


2


CH


2


CO


2


H




H




Cl




CH




O






1-315




CO


2


CH


2


CO


2


H




Cl




H




CH




O






1-316




CO


2


CH


2


CO


2


H




H




NO


2






CH




O






1-317




CO


2


CH


2


CO


2


H




NO


2






H




CH




O






1-318




CO


2


CH


2


CO


2


Me




H




H




CH




O



























TABLE 14









Compound




R


2






R


3






R


4






A




Y











1-319




CO


2


CH


2


CO


2


Me




H




Cl




CH




O






1-320




CO


2


CH


2


CO


2


Me




Cl




H




CH




O






1-321




CO


2


CH


2


CO


2


Me




H




NO


2






CH




O






1-322




CO


2


CH


2


CO


2


Me




NO


2






H




CH




O






1-323




CO


2


CH


2


CO


2


Et




H




H




CH




O






1-324




CO


2


CH


2


CO


2


Et




H




Cl




CH




O






1-325




CO


2


CH


2


CO


2


Et




Cl




H




CH




O






1-326




CO


2


CH


2


CO


2


Et




H




NO


2






CH




O






1-327




CO


2


CH


2


CO


2


Et




NO


2






H




CH




O






1-328




CO


2


CH(CH


3


)CO


2


H




H




H




CH




O






1-329




CO


2


CH(CH


3


)CO


2


H




H




Cl




CH




O






1-330




CO


2


CH(CH


3


)CO


2


H




Cl




H




CH




O






1-331




CO


2


CH(CH


3


)CO


2


H




H




NO


2






CH




O






1-332




CO


2


CH(CH


3


)CO


2


H




NO


2






H




CH




O






1-333




CO


2


CH(CH


3


)CO


2


Me




H




H




CH




O






1-334




CO


2


CH(CH


3


)CO


2


Me




H




Cl




CH




O






1-335




CO


2


CH(CH


3


)CO


2


Me




Cl




H




CH




O






1-336




CO


2


CH(CH


3


)CO


2


Me




H




NO


2






CH




O






1-337




CO


2


CH(CH


3


)CO


2


Me




NO


2






H




CH




O






1-338




CO


2


CH(CH


3


)CO


2


Et




H




H




CH




O






1-339




CO


2


CH(CH


3


)CO


2


Et




H




Cl




CH




O






1-340




CO


2


CH(CH


3


)CO


2


Et




Cl




H




CH




O






1-341




CO


2


CH(CH


3


)CO


2


Et




H




NO


2






CH




O






1-342




CO


2


CH(CH


3


)CO


2


Et




NO


2






H




CH




O






1-343




CO


2


C(CH


3


)


2


CO


2


H




H




H




CH




O



























TABLE 15









Compound




R


2






R


3






R


4






A




Y











1-344




CO


2


C(CH


3


)


2


CO


2


H




H




Cl




CH




O






1-345




CO


2


C(CH


3


)


2


CO


2


H




Cl




H




CH




O






1-346




CO


2


C(CH


3


)


2


CO


2


H




H




NO


2






CH




O






1-347




CO


2


C(CH


3


)


2


CO


2


H




NO


2






H




CH




O






1-348




CO


2


C(CH


3


)


2


CO


2


Me




H




H




CH




O






1-349




CO


2


C(CH


3


)


2


CO


2


Me




H




Cl




CH




O






1-350




CO


2


C(CH


3


)


2


CO


2


Me




Cl




H




CH




O






1-351




CO


2


C(CH


3


)


2


CO


2


Me




H




NO


2






CH




O






1-352




CO


2


C(CH


3


)


2


CO


2


Me




NO


2






H




CH




O






1-353




CO


2


C(CH


3


)


2


CO


2


Et




H




Cl




CH




O






1-354




CO


2


C(CH


3


)


2


CO


2


Et




Cl




H




CH




O






1-355




CO


2


C(CH


3


)


2


CO


2


Et




H




NO


2






CH




O






1-356




CO


2


C(CH


3


)


2


CO


2


Et




NO


2






H




CH




O






1-357




CH


3






H




H




CH




O






1-358




CH


3






H




Cl




CH




O






1-359




CH


3






GI




H




CH




O






1-360




CH


3






H




NO


2






CH




O






1-361




CH


3






NO


2






H




CH




O






1-362




CF


3






H




H




CH




O






1-363




CF


3






H




Cl




CH




O






1-364




CF


3






Cl




H




CH




O






1-365




CF


3






H




NO


2






CH




O






1-366




CF


3






NO


2






H




CH




O






1-367




CH═CHCO


2


H




H




H




CH




O



























TABLE 16









Compound




R


2






R


3






R


4






A




Y











1-368




CH═CHCO


2


H




H




Cl




CH




O






1-369




CH═CHCO


2


H




Cl




H




CH




O






1-370




CH═CHCO


2


H




H




NO


2






CH




O






1-371




CH═CHCO


2


H




NO


2






H




CH




O






1-372




CH═CHCO


2


Me




H




H




CH




O






1-373




CH═CHCO


2


Me




H




Cl




CH




O






1-374




CH═CHCO


2


Me




Cl




H




CH




O






1-375




CH═CHCO


2


Me




H




NO


2






CH




O






1-376




CH═CHCO


2


Me




NO


2






H




CH




O






1-377




CH═CHCO


2


Et




H




H




CH




O






1-378




CH═CHCO


2


Et




H




Cl




CH




O






1-379




CH═CHCO


2


Et




Cl




H




CH




O






1-380




CH═CHCO


2


Et




H




NO


2






CH




O






1-381




CH═CHCO


2


Et




NO


2






H




CH




O






1-382




CH


2


CH


2


CO


2


H




H




H




CH




O






1-383




CH


2


CH


2


CO


2


H




H




Cl




CH




O






1-384




CH


2


CH


2


CO


2


H




Cl




H




CH




O






1-385




CH


2


CH


2


CO


2


H




H




NO


2






CH




O






1-386




CH


2


CH


2


CO


2


H




NO


2






H




CH




O






1-387




CH


2


CH


2


CO


2


Me




H




H




CH




O






1-388




CH


2


CH


2


CO


2


Me




H




Cl




CH




O






1-389




CH


2


CH


2


CO


2


Me




Cl




H




CH




O






1-390




CH


2


CH


2


CO


2


Me




H




NO


2






CH




O






1-391




CH


2


CH


2


CO


2


Me




NO


2






H




CH




O






1-392




CH


2


CH


2


CO


2


Et




H




H




CH




O



























TABLE 17









Compound




R


2






R


3






R


4






A




Y











1-393




CH


2


CH


2


CO


2


Et




H




Cl




CH




O






1-394




CH


2


CH


2


CO


2


Et




Cl




H




CH




O






1-395




CH


2


CH


2


CO


2


Et




H




NO


2






CH




O






1-396




CH


2


CH


2


CO


2


Et




NO


2






H




CH




O






1-397




CH


2


CH(Cl)CO


2


H




H




H




CH




O






1-398




CH


2


CH(Cl)CO


2


H




H




Cl




CH




O






1-399




CH


2


CH(Cl)CO


2


H




Cl




H




CH




O






1-400




CH


2


CH(Cl)CO


2


H




H




NO


2






CH




O






1-401




CH


2


CH(Cl)CO


2


H




NO


2






H




CH




O






1-402




CH


2


CH(Cl)CO


2


Me




H




H




CH




O






1-403




CH


2


CH(Cl)CO


2


Me




H




Cl




CH




O






1-404




CH


2


CH(Cl)CO


2


Me




Cl




H




CH




O






1-405




CH


2


CH(Cl)CO


2


Me




H




NO


2






CH




O






1-406




CH


2


CH(Cl)CO


2


Me




NO


2






H




CH




O






1-407




CH


2


CH(Cl)CO


2


Et




H




H




CH




O






1-408




CH


2


CH(Cl)CO


2


Et




H




Cl




CH




O






1-409




CH


2


CH(Cl)CO


2


Et




Cl




H




CH




O






1-410




CH


2


CH(Cl)CO


2


Et




H




NO


2






CH




O






1-411




CH


2


CH(Cl)CO


2


Et




NO


2






H




CH




O






1-412




C(═O)CH


3






H




H




CH




O






1-413




C(═O)CH


3






H




Cl




CH




O






1-414




C(═O)CH


3






Cl




H




CH




O






1-415




C(═O)CH


3






H




NO


2






CH




O






l-416




C(═O)CH


3






NO


2






H




CH




O






1-417




C(CH


3


)═NOH




H




H




CH




O



























TABLE 18









Compound




R


2






R


3






R


4






A




Y











1-418




C(CH


3


)═NOH




H




Cl




CH




O






1-419




C(CH


3


)═NOH




Cl




H




CH




O






1-420




C(CH


3


)═NOH




H




NO


2






CH




O






1-421




C(CH


3


)═NOH




NO


2






H




CH




O






1-422




C(CH


3


)═NOMe




H




H




CH




O






1-423




C(CH


3


)═NOMe




H




Cl




CH




O






1-424




C(CH


3


)═NOMe




Cl




H




CH




O






1-425




C(CH


3


)═NOMe




H




NO


2






CH




O






1-426




C(CH


3


)═NOMe




NO


2






H




CH




O






1-427




F




H




H




CH




O






1-428




F




H




Cl




CH




O






1-429




F




Cl




H




CH




O






1-430




F




H




NO


2






CH




O






1-431




F




NO


2






H




CH




O






1-432




Cl




H




Cl




CH




S






1-433




Cl




H




H




CH




S






1-434




OCH


3






H




H




CH




S






1-435




NO


2






H




H




CH




S






1-436




NH


2






H




H




CH




S






1-437




NHCH


3






H




H




CH




S






1-438




N(CH


3


)


2






H




H




CH




S






1-439




NHSO


2


CH


3






H




H




CH




S






1-440




NHCH(CH


3


)CO


2


Et




H




H




CH




S






1-441




NHCH(CH


3


)CO


2


Et




H




Cl




CH




S






1-442




N(CH


3


)CH(CH


3


)CO


2


Et




H




Cl




CH




S



























TABLE 19









Compound




R


2






R


3






R


4






A




Y











1-443




N(CH


3


)SO


2


CH


3






H




Cl




CH




S






1-444




NHSO


2


CH


3






H




Cl




CH




S






1-445




NHCH(CH


3


)CO


2


Et




Cl




H




CH




S






1-446




N(CH


3


)CH(CH


3


)CO


2


Et




Cl




H




CH




S






1-447




N(CH


3


)SO


2


CH


3






Cl




H




CH




S






1-448




NHSO


2


CH


3






Cl




H




CH




S






1-449




NO


2






H




Cl




CH




S






1-450




NH


2






H




Cl




CH




S






1-451




NO


2






Cl




H




CH




S






1-452




NH


2






Cl




H




CH




S






1-453




NHCOCH


3






H




H




CH




S






1-454




NHCOCF


3






H




H




CH




S






1-455




NHSO


2


Et




H




H




CH




S






1-456




NHSO


2


CH


2


Cl




H




H




CH




S






1-457




N(CH


3


)COCH


3






H




H




CH




S






1-458




N(CH


3


)COCF


3






H




H




CH




S






1-459




N(CH


3


)SO


2


Et




H




H




CH




S






1-460




N(CH)SO


2


CH


2


Cl




H




H




CH




S






1-461




NHCOCH


3






H




Cl




CH




S






1-462




NHCOCF


3






H




Cl




CH




S






1-463




NHSO


2


Et




H




Cl




CH




S






1-464




NHSO


2


CH


2


Cl




H




Cl




CH




S






1-465




N(CH


3


)COCH


3






Cl




H




CH




S






1-466




N(CH


3


)COCF


3






Cl




H




CH




S






1-467




N(CH


3


)SO


2


Et




Cl




H




CH




S



























TABLE 20









Compound




R


2






R


3






R


4






A




Y











1-468




N(CH


3


)SO


2


CH


2


Cl




Cl




H




CH




S






1-469




NHCH


2


CO


2


Me




H




H




CH




S






1-470




NHCH


2


CO


2


Et




H




H




CH




S






1-471




NHCH(CH


3


)COOH




H




H




CH




S






1-472




NHCH(CH


3


)CONH


2






H




H




CH




S






1-473




NHCH(CH


3


)CONHCH


3






H




H




CH




S






1-474




NHCH


2


CO


2


Me




H




Cl




CH




S






1-475




NHCH


2


CO


2


Et




H




Cl




CH




S






1-476




NHCH(CH


3


)COOH




H




Cl




CH




S






1-477




NHCH(CH


3


)CONH


2






H




Cl




CH




S






1-478




NHCH(CH


3


)CONHCH


3






H




Cl




CH




S






1-479




NHCH


2


CO


2


Me




Cl




H




GH




S






1-480




NHCH


2


CO


2


Et




Cl




H




CH




S






1-481




NHCH(CH


3


)COOH




Cl




H




CH




S






1-482




NHCH(CH


3


)CONH


2






Cl




H




CH




S






1-483




NHCH(CH


3


)CONHCH


3






Cl




H




CH




S






1-484




NHCH


2


CH


2


CH


3






H




H




CH




S






1-485




NHCH


2


CH═CH


2






H




H




CH




S






1-486




NHCH


2


C≡CH




H




H




CH




S






1-487




N(CH


3


)CH


2


CH


2


CH


3






H




H




CH




S






1-488




N(CH


3


)CH


2


CH═CH


2






H




H




CH




S






1-489




N(CH


3


)CH


2


C≡CH




H




H




CH




S






1-490




NHCH


2


CH


2


CH


3






H




Cl




CH




S






1-491




NHCH


2


CH═CH


2






H




Cl




CH




S






1-492




NHCH


2


C≡CH




H




Cl




CH




S



























TABLE 21









Compound




R


2






R


3






R


4






A




Y











1-493




N(CH


3


)CH


2


CH


2


CH


3






H




Cl




CH




S






1-494




N(CH


3


)CH


2


CH═CH


2






H




Cl




CH




S






1-495




N(CH


3


)CH


2


C≡CH




H




Cl




CH




S






1-496




NHCH


2


CH


2


CH


3






Cl




H




CH




S






1-497




NHCH


2


CH═CH


2






Cl




H




CH




S






1-498




NHCH


2


C≡CH




Cl




H




CH




S






1-499




N(CH


3


)CH


2


CH


2


CH


3






Cl




H




CH




S






1-500




N(CH


3


)CH


2


CH═CH


2






Cl




H




CH




S






1-501




N(CH


3


)CH


2


C≡CH




Cl




H




CH




S






1-502




Br




H




H




CH




S






1-503




Br




H




Cl




CH




S






1-504




Br




Cl




H




CH




S






1-505




OH




H




H




CH




S






1-506




OH




H




Cl




CH




S






1-507




OH




Cl




H




CH




S






1-508




OH




H




NO


2






CH




S






1-509




OH




NO


2






H




CH




S






1-510




OCH


3






H




Cl




CH




S






1-511




OCH


3






Cl




H




CH




S






1-512




OCH


3






H




NO


2






CH




S






1-513




OCH


3






NO


2






H




CH




S






1-514




OCH(CH


3


)CH


3






H




H




CH




S






1-515




OCH(CH


3


)CH


3






H




Cl




CH




S






1-516




OCH(CH


3


)CH


3






Cl




H




CH




S






1-517




OCH(CH


3


)CH


3






H




NO


2






CH




S



























TABLE 22









Compound




R


2






R


3






R


4






A




Y











1-518




OCH(CH


3


)CH


3






NO


2






H




CH




S






1-519




OCH


2


CH═CH


2






H




H




CH




S






1-520




OCH


2


CH═CH


2






H




Cl




CH




S






1-521




OCH


2


CH═CH


2






Cl




H




CH




S






1-522




OCH


2


CH═CH


2






H




NO


2






CH




S






1-523




OCH


2


CH═CH


2






NO


2






H




CH




S






1-524




OCH(CH


3


)CH═CH


2






H




H




CH




S






1-525




OCH(CH


3


)CH═CH


2






H




Cl




CH




S






1-526




OCH(CH


3


)CH═CH


2






Cl




H




CH




S






1-527




OCH(CH


3


)CH═CH


2






H




NO


2






CH




S






1-528




OCH(CH


3


)CH═CH


2






NO


2






H




CH




S






1-529




OCH


2


C(Cl)═CH


2






H




H




CH




S






1-530




OCH


2


C(Cl)═CH


2






H




Cl




CH




S






1-531




OCH


2


C(Cl)═CH


2






Cl




H




CH




S






1-532




OCH


2


C(Cl)═CH


2






H




NO


2






CH




S






1-533




OCH


2


C(Cl)═CH


2






NO


2






H




CH




S






1-534




OCH


2


C≡CH




H




H




CH




S






1-535




OCH


2


C≡CH




H




Cl




CH




S






1-536




OCH


2


C≡CH




Cl




H




CH




S






1-537




OCH


2


C≡CH




H




NO


2






CH




S






1-538




OCH


2


C≡CH




NO


2






H




CH




S






1-539




OCH(CH


3


)C≡CH




H




H




CH




S






1-540




OCH(CH


3


)C≡CH




H




Cl




CH




S






1-541




OCH(CH


3


)C≡CH




Cl




H




CH




S






1-542




OCH(CH


3


)C≡CH




H




NO


2






CH




S



























TABLE 23









Compound




R


2






R


3






R


4






A




Y











1-543




OCH(CH


3


)C≡CH




NO


2






H




CH




S






1-544




OCH(CH


3


)COOH




H




H




CH




S






1-545




OCH(CH


3


)COOH




H




Cl




CH




S






1-546




OCH(CH


3


)COOH




Cl




H




CH




S






1-547




OCH(CH


3


)COOH




H




NO


2






CH




S






1-548




OCH(CH


3


)COOH




NO


2






H




CH




S






1-549




OCH(CH


3


)COOMe




H




H




CH




S






1-550




OCH(CH


3


)COOMe




H




Cl




CH




S






1-551




OCH(CH


3


)COOMe




Cl




H




CH




S






1-552




OCH(CH


3


)COOMe




H




NO


2






CH




S






1-553




OCH(CH


3


)COOMe




NO


2






H




CH




S






1-554




OCH(CH


3


)COOEt




H




H




CH




S






1-555




OCH(CH


3


)COOEt




H




Cl




CH




S






1-556




OCH(CH


3


)COOEt




Cl




H




CH




S






1-557




OCH(CH


3


)COOEt




H




NO


2






CH




S






1-558




OCH(CH


3


)COOEt




NO


2






H




CH




S






1-559




OCH(CH


3


)COOPr




H




H




CH




S






1-560




OCH(CH


3


)COOPr




H




Cl




CH




S






1-561




OCH(CH


3


)COOPr




Cl




H




CH




S






1-562




OCH(CH


3


)COOPr




H




NO


2






CH




S






1-563




OCH(CH


3


)COOPr




NO


2






H




CH




S






1-564




OCH(CH


3


)COO-i-Pr




H




H




CH




S






1-565




OCH(CH


3


)COO-i-Pr




H




Cl




CH




S






1-566




OCH(CH


3


)COO-i-Pr




Cl




H




CH




S






1-567




OCH(CH


3


)COO-i-Pr




H




NO


2






CH




S



























TABLE 24









Compound




R


2






R


3






R


4






A




Y











1-568




OCH(CH


3


)COO-i-Pr




NO


2






H




CH




S






1-569




OCH(CH


3


)COOBu




H




H




CH




S






1-570




OCH(CH


3


)COOBu




H




Cl




CH




S






1-571




OCH(CH


3


)COOBu




Cl




H




CH




S






1-572




OCH(CH


3


)COOBu




H




NO


2






CH




S






1-573




OCH(CH


3


)COOBu




NO


2






H




CH




S






1-574




OCH(CH


3


)COOPen




H




H




CH




S






1-575




OCH(CH


3


)COOPen




H




Cl




CH




S






1-576




OCH(CH


3


)COOPen




Cl




H




CH




S






1-577




DCH(CH


3


)COOPen




H




NO


2






CH




S






1-578




OCH(CH


3


)COOPen




NO


2






H




CH




S






1-579




OCH(CH


3


)COO-c-Pen




H




H




CH




S






1-580




OCH(CH


3


)COO-c-Pen




H




Cl




CH




S






1-581




OCH(CH


3


)COO-c-Pen




Cl




H




CH




S






1-582




OCH(CH


3


)COO-c-Pen




H




NO


2






CH




S






1-583




OCH(CH


3


)COO-c-Pen




NO


2






H




CH




S






1-584




OCH(CH


3


)COOHex




H




H




CH




S






1-585




OCH(CH


3


)COOHex




H




Cl




CH




S






1-586




OCH(CH


3


)COOHex




Cl




H




CH




S






1-587




OCH(CH


3


)COOHex




H




NO


2






CH




S






1-588




OCH(CH


3


)COOHex




NO


2






H




CH




S






1-589




OCH(CH


3


)COO-c-Hex




H




H




CH




S






1-590




OCH(CH


3


)COO-c-Hex




H




Cl




CH




S






1-591




OCH(CH


3


)COO-c-Hex




Cl




H




CH




S






1-592




OCH(CH


3


)COO-c-Hex




H




NO


2






CH




S



























TABLE 25









Com-











pound




R


2






R


3






R


4






A




Y











1-593




OCH(CH


3


)COO-c-Hex




NO


2






H




CH




S






1-594




OCH(CH


3


)CO


2


CH


2


CO


2


H




H




H




CH




S






1-595




OCH(CH


3


)CO


2


CH


2


CO


2


H




H




Cl




CH




S






1-596




OCH(CH


3


)CO


2


CH


2


CO


2


H




Cl




H




CH




S






1-597




OCH(CH


3


)CO


2


CH


2


CO


2


H




H




NO


2






CH




S






1-598




OCH(CH


3


)CO


2


CH


2


CO


2


H




NO


2






H




CH




S






1-599




OCH(CH


3


)CO


2


CH


2


CO


2


Me




H




H




CH




S






1-600




OCH(CH


3


)CO


2


CH


2


CO


2


Me




H




Cl




CH




S






1-601




OCH(CH


3


)CO


2


CH


2


CO


2


Me




Cl




H




CH




S






1-602




OCH(CH


3


)CO


2


CH


2


CO


2


Me




H




NO


2






CH




S






1-603




OCH(CH


3


)CO


2


CH


2


CO


2


Me




NO


2






H




CH




S






1-604




OCH(CH


3


)CO


2


CH


2


CO


2


Et




H




H




CH




S






1-605




OCH(CH


3


)CO


2


CH


2


CO


2


Et




H




Cl




CH




S






1-606




OCH(CH


3


)CO


2


CH


2


CO


2


Et




Cl




H




CH




S






1-607




OCH(CH


3


)CO


2


CH


2


CO


2


Et




H




NO


2






CH




S






1-608




OCH(CH


3


)CO


2


CH


2


CO


2


Et




NO


2






H




CH




S






1-609




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




H




CH




S






1-610




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




Cl




CH




S






1-611




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




Cl




H




CH




S






1-612




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




NO


2






CH




S






1-613




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




NO


2






H




CH




S






1-614




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




H




CH




S






1-615




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




Cl




CH




S






1-616




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




Cl




H




CH




S






1-617




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




NO


2






CH




S



























TABLE 26









Com-











pound




R


2






R


3






R


4






A




Y




























1-618




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




NO


2






H




CH




S






1-619




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




H




CH




S






1-620




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




Cl




CH




S






1-621




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




Cl




H




CH




S






1-622




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




NO


2






CH




S






1-623




OCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




NO


2






H




CH




S






1-624




SCH


3






H




H




CH




S






1-625




SCH


3






H




Cl




CH




S






1-626




SCH


3






Cl




H




CH




S






1-627




SCH


3






H




NO


2






CH




S






1-628




SCH


3






NO


2






H




CH




S






1-629




SCH(CH


3


)CH


3






H




H




CH




S






1-630




SCH(CH


3


)CH


3






H




Cl




CH




S






1-631




SCH(CH


3


)CH


3






Cl




H




CH




S






1-632




SCH(CH


3


)CH


3






H




NO


2






CH




S






1-633




SCH(CH


3


)CH


3






NO


2






H




CH




S






1-634




SCHCH═CH


2






H




H




CH




S






1-635




SCHCH═CH


2






H




Cl




CH




S






1-636




SCHCH═CH


2






Cl




H




CH




S






1-637




SCHCH═CH


2






H




NO


2






CH




S






1-638




SCHCH═CH


2






NO


2






H




CH




S






1-639




SCHC≡CH




H




H




CH




S






1-640




SCHC≡CH




H




Cl




CH




S






1-641




SCHC≡CH




Cl




H




CH




S






1-642




SCHC≡CH




H




NO


2






CH




S



























TABLE 27









Compound




R


2






R


3






R


4






A




Y











1-643




SCHC≡CH




NO


2






H




CH




S






1-644




SCH


2


COOH




H




H




CH




S






1-645




SCH


2


COOH




H




Cl




CH




S






1-646




SCH


2


COOH




Cl




H




CH




S






1-647




SCH


2


COOH




H




NO


2






CH




S






1-648




SCH


2


COOH




NO


2






H




CH




S






1-649




SCH


2


COOMe




H




H




CH




S






1-650




SCH


2


COOMe




H




Cl




CH




S






1-651




SCH


2


COOMe




Cl




H




CH




S






1-652




SCH


2


COOMe




H




NO


2






CH




S






1-653




SCH


2


COOMe




NO


2






H




CH




S






1-654




SCH


2


COOEt




H




H




CH




S






1-655




SCH


2


COOEt




H




Cl




CH




S






1-656




SCH


2


COOEt




Cl




H




CH




S






1-657




SCH


2


COOEt




H




NO


2






CH




S






1-658




SCH


2


COOEt




NO


2






H




CH




S






1-659




SCH(CH


3


)COOH




H




H




CH




S






1-660




SCH(CH


3


)COOH




H




Cl




CH




S






1-661




SCH(CH


3


)COOH




Cl




H




CH




S






1-662




SCH(CH


3


)COOH




H




NO


2






CH




S






1-663




SCH(CH


3


)COOH




NO


2






H




CH




S






1-664




SCH(CH


3


)COOMe




H




H




CH




S






1-665




SCH(CH


3


)COOMe




H




Cl




CH




S






1-666




SCH(CH


3


)COOMe




Cl




H




CH




S






1-667




SCH(CH


3


)COOMe




H




NO


2






CH




S



























TABLE 28









Compound




R


2






R


3






R


4






A




Y











1-668




SCH(CH


3


)COOMe




NO


2






H




CH




S






1-669




SCH(CH


3


)COOEt




H




H




CH




S






1-670




SCH(CH


3


)COOEt




H




Cl




CH




S






1-671




SCH(CH


3


)COOEt




Cl




H




CH




S






1-672




SCH(CH


3


)COOEt




H




NO


2






CH




S






1-673




SCH(CH


3


)COOEt




NO


2






H




CH




S






1-674




SCH(CH


3


)COO-i-Pr




H




H




CH




S






1-675




SCH(CH


3


)COO-i-Pr




H




Cl




CH




S






1-676




SCH(CH


3


)COO-i-Pr




Cl




H




CH




S






1-677




SCH(CH


3


)COO-i-Pr




H




NO


2






CH




S






1-678




SCH(CH


3


)COO-i-Pr




NO


2






H




CH




S






1-679




SCH(CH


3


)CO


2


CH


2


CO


2


H




H




H




CH




S






1-680




SCH(CH


3


)CO


2


CH


2


CO


2


H




H




Cl




CH




S






1-681




SCH(CH


3


)CO


2


CH


2


CO


2


H




Cl




H




CH




S






1-682




SCH(CH


3


)CO


2


CH


2


CO


2


H




H




NO


2






CH




S






1-683




SCH(CH


3


)CO


2


CH


2


CO


2


H




NO


2






H




CH




S






1-684




SCH(CH


3


)CO


2


CH


2


CO


2


Me




H




H




CH




S






1-685




SCH(CH


3


)CO


2


CH


2


CO


2


Me




H




Cl




CH




S






1-686




SCH(CH


3


)CO


2


CH


2


CO


2


Me




Cl




H




CH




S






1-687




SCH(CH


3


)CO


2


CH


2


CO


2


Me




H




NO


2






CH




S






1-688




SCH(CH


3


)CO


2


CH


2


CO


2


Me




NO


2






H




CH




S






1-689




SCH(CH


3


)CO


2


CH


2


CO


2


Et




H




H




CH




S






1-690




SCH(CH


3


)CO


2


CH


2


CO


2


Et




H




Cl




CH




S






1-691




SCH(CH


3


)CO


2


CH


2


CO


2


Et




Cl




H




OH




S






1-692




SCH(CH


3


)CO


2


CH


2


CO


2


Et




H




NO


2






CH




S



























TABLE 29









Com-











pound




R


2






R


3






R


4






A




Y











1-693




SCH(CH


3


)CO


2


CH


2


CO


2


Et




NO


2






H




CH




S






1-694




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




H




CH




S






1-695




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




Cl




CH




S






1-696




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




Cl




H




CH




S






1-697




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




H




NO


2






CH




S






1-698




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


H




NO


2






H




CH




S






1-699




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




H




CH




S






1-700




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




Cl




CH




S






1-701




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




Cl




H




CH




S






1-702




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




H




NO


2






CH




S






1-703




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Me




NO


2






H




CH




S






1-704




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




H




CH




S






1-705




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




Cl




CH




S






1-706




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




Cl




H




CH




S






1-707




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




H




NO


2






CH




S






1-708




SCH(CH


3


)CO


2


CH(CH


3


)CO


2


Et




NO


2






H




CH




S






1-709




H




NO


2






H




CH




S






1-710




C≡N




H




H




CH




S






1-711




C≡N




H




Cl




CH




S






1-712




C≡N




Cl




H




CH




S






1-713




C≡N




H




NO


2






CH




S






1-714




C≡N




NO


2






H




CH




S






1-715




C(═O)H




H




H




CH




S






1-716




C(═O)H




H




Cl




CH




S






1-717




C(═O)H




Cl




H




CH




S



























TABLE 30









Compound




R


2






R


3






R


4






A




Y











1-718




C(═O)H




H




NO


2






CH




S






1-719




C(═O)H




NO


2






H




CH




S






1-720




C(═O)NH


2






H




H




CH




S






1-721




C(═O)NH


2






H




Cl




CH




S






1-722




C(═O)NH


2






Cl




H




CH




S






1-723




C(═O)NH


2






H




NO


2






CH




S






1-724




C(═O)NH


2






NO


2






H




CH




S






1-725




CO


2


H




H




H




CH




S






1-726




CO


2


H




H




Cl




CH




S






1-727




CO


2


H




Cl




H




CH




S






1-728




CO


2


H




H




NO


2






CH




S






1-729




CO


2


H




NO


2






H




CH




S






1-730




CO


2


Me




H




H




CH




S






1-731




CO


2


Me




H




Cl




CH




S






1-732




CO


2


Me




Cl




H




CH




S






1-733




CO


2


Me




H




NO


2






CH




S






1-734




CO


2


Me




NO


2






H




CH




S






1-735




CO


2


Et




H




H




CH




S






1-736




CO


2


Et




H




Cl




CH




S






1-737




CO


2


Et




Cl




H




CH




S






1-738




CO


2


Et




H




NO


2






CH




S






1-739




CO


2


Et




NO


2






H




CH




S






1-740




CO


2


CH


2


CO


2


H




H




H




CH




S






1-741




CO


2


CH


2


CO


2


H




H




Cl




CH




S






1-742




CO


2


CH


2


CO


2


H




Cl




H




CH




S



























TABLE 31









Compound




R


2






R


3






R


4






A




Y











1-743




CO


2


CH


2


CO


2


H




H




NO


2






CH




S






1-744




CO


2


CH


2


CO


2


H




NO


2






H




CH




S






1-745




CO


2


CH


2


CO


2


Me




H




H




CH




S






1-746




CO


2


CH


2


CO


2


Me




H




Cl




CH




S






1-747




CO


2


CH


2


CO


2


Me




Cl




H




CH




S






1-748




CO


2


CH


2


CO


2


Me




H




NO


2






CH




S






1-749




CO


2


CH


2


CO


2


Me




NO


2






H




CH




S






1-750




CO


2


CH


2


CO


2


Et




H




H




CH




S






1-751




CO


2


CH


2


CO


2


Et




H




Cl




CH




S






1-752




CO


2


CH


2


CO


2


Et




Cl




H




CH




S






1-753




CO


2


CH


2


CO


2


Et




H




NO


2






CH




S






1-754




CO


2


CH


2


CO


2


Et




NO


2






H




CH




S






1-755




CO


2


CH(CH


3


)CO


2


H




H




H




CH




S






1-756




CO


2


CH(CH


3


)CO


2


H




H




Cl




CH




S






1-757




CO


2


CH(CH


3


)CO


2


H




Cl




H




CH




S






1-758




CO


2


CH(CH


3


)CO


2


H




H




NO


2






CH




S






1-759




CO


2


CH(CH


3


)CO


2


H




NO


2






H




CH




S






1-760




CO


2


CH(CH


3


)CO


2


Me




H




H




CH




S






1-761




CO


2


CH(CH


3


)CO


2


Me




H




Cl




CH




S






1-762




CO


2


CH(CH


3


)CO


2


Me




Cl




H




CH




S






1-763




CO


2


CH(CH


3


)CO


2


Me




H




NO


2






CH




S






1-764




CO


2


CH(CH


3


)CO


2


Me




NO


2






H




CH




S






1-765




CO


2


CH(CH


3


)CO


2


Et




H




H




CH




S






1-766




CO


2


CH(CH


3


)CO


2


Et




H




Cl




CH




S






1-767




CO


2


CH(CH


3


)CO


2


Et




Cl




H




CH




S





























TABLE 32











Compound




R


2






R


3






R


4






A




Y













1-768




CO


2


CH(CH


3


)CO


2


Et




H




NO


2






CH




S







1-769




CO


2


CH(CH


3


)CO


2


Et




NO


2






H




CH




S







1-770




CO


2


C(CH


3


)


2


CO


2


H




H




H




CH




S







1-771




CO


2


C(CH


3


)


2


CO


2


H




H




Cl




CH




S







1-772




CO


2


C(CH


3


)


2


CO


2


H




Cl




H




CH




S







1-773




CO


2


C(CH


3


)


2


CO


2


H




H




NO


2






CH




S







1-774




CO


2


C(CH


3


)


2


CO


2


H




NO


2






H




CH




S







1-775




CO


2


C(CH


3


)


2


CO


2


Me




H




H




CH




S







1-776




CO


2


C(CH


3


)


2


CO


2


Me




H




Cl




CH




S







1-777




CO


2


C(CH


3


)


2


CO


2


Me




Cl




H




CH




S







1-778




CO


2


C(CH


3


)


2


CO


2


Me




H




NO


2






CH




S







1-779




CO


2


C(CH


3


)


2


CO


2


Me




NO


2






H




CH




S







1-780




CO


2


C(CH


3


)


2


CO


2


Et




H




H




CH




S







1-781




CO


2


C(CH


3


)


2


CO


2


Et




H




Cl




CH




S







1-782




CO


2


C(CH


3


)


2


CO


2


Et




Cl




H




CH




S







1-783




CO


2


C(CH


3


)


2


CO


2


Et




H




NO


2






CH




S







1-784




CO


2


C(CH


3


)


2


CO


2


Et




NO


2






H




CH




S







1-785




CH


3






H




H




CH




S







1-786




CH


3






H




Cl




CH




S







1-787




CH


3






Cl




H




CH




S







1-788




CH


3






H




NO


2






CH




S







1-789




CH


3






NO


2






H




CH




S







1-790




CF


3






H




H




CH




S







1-791




CF


3






H




Cl




CH




S







1-792




CF


3






Cl




H




CH




S






























TABLE 33











Compound




R


2






R


3






R


4






A




Y













1-793




CF


3






H




NO


2






CH




S







1-794




CF


3






NO


2






H




CH




S







1-795




CH═CHCO


2


H




H




H




CH




S







1-796




CH═CHCO


2


H




H




Cl




CH




S







1-797




CH═CHCO


2


H




Cl




H




CH




S







1-798




CH═CHCO


2


H




H




NO


2






CH




S







1-799




CH═CHCO


2


H




NO


2






H




CH




S







1-800




CH═CHCO


2


Me




H




H




CH




S







1-801




CH═CHCO


2


Me




H




Cl




CH




S







1-802




CH═CHCO


2


Me




Cl




H




CH




S







1-803




CH═CHCO


2


Me




H




NO


2






CH




S







1-804




CH═CHCO


2


Me




NO


2






H




CH




S







1-805




CH═CHCO


2


Et




H




H




CH




S







1-806




CH═CHCO


2


Et




H




Cl




CH




S







1-807




CH═CHCO


2


Et




Cl




H




CH




S







1-808




CH═CHCO


2


Et




H




NO


2






CH




S







1-809




CH═CHCO


2


Et




NO


2






H




CH




S







1-810




CH


2


CH


2


CO


2


H




H




H




CH




S







1-811




CH


2


CH


2


CO


2


H




H




Cl




CH




S







1-812




CH


2


CH


2


CO


2


H




Cl




H




CH




S







1-813




CH


2


CH


2


CO


2


H




H




NO


2






CH




S







1-814




CH


2


CH


2


CO


2


H




NO


2






H




CH




S







1-815




CH


2


CH


2


CO


2


Me




H




H




CH




S







1-816




CH


2


CH


2


CO


2


Me




H




Cl




CH




S







1-817




CH


2


CH


2


CO


2


Me




Cl




H




CH




S






























TABLE 34











Compound




R


2






R


3






R


4






A




Y













1-818




CH


2


CH


2


CO


2


Me




H




NO


2






CH




S







1-819




CH


2


CH


2


CO


2


Me




NO


2






H




CH




S







1-820




CH


2


CH


2


CO


2


Et




H




H




CH




S







1-821




CH


2


CH


2


CO


2


Et




H




Cl




CH




S







1-822




CH


2


CH


2


CO


2


Et




Cl




H




CH




S







1-823




CH


2


CH


2


CO


2


Et




H




NO


2






CH




S







1-824




CH


2


CH


2


CO


2


Et




NO


2






H




CH




S







1-825




CH


2


CH(Cl)CO


2


H




H




H




CH




S







1-826




CH


2


CH(Cl)CO


2


H




H




Cl




CH




S







1-827




CH


2


CH(Cl)CO


2


H




Cl




H




CH




S







1-828




CH


2


CH(Cl)CO


2


H




H




NO


2






CH




S







1-829




CH


2


CH(Cl)CO


2


H




NO


2






H




CH




S







1-830




CH


2


CH(Cl)CO


2


Me




H




H




CH




S







1-831




CH


2


CH(Cl)CO


2


Me




H




Cl




CH




S







1-832




CH


2


CH(Cl)CO


2


Me




Cl




H




CH




S







1-833




CH


2


CH(Cl)CO


2


Me




H




NO


2






CH




S







1-834




CH


2


CH(Cl)CO


2


Me




NO


2






H




CH




S







1-835




CH


2


CH(Cl)CO


2


Et




H




H




CH




S







1-836




CH


2


CH(Cl)CO


2


Et




H




Cl




CH




S







1-837




CH


2


CH(Cl)CO


2


Et




Cl




H




CH




S







1-838




CH


2


CH(Cl)CO


2


Et




H




NO


2






CH




S







1-839




CH


2


CH(Cl)CO


2


Et




NO


2






H




CH




S







1-840




C(═O)CH


3






H




H




CH




S







1-841




C(═O)CH


3






H




Cl




CH




S







1-842




C(═O)CH


3






Cl




H




CH




S






























TABLE 35











Compound




R


2






R


3






R


4






A




Y













1-843




C(═O)CH


3






H




NO


2






CH




S







1-844




C(═O)CH


3






NO


2






H




CH




S







1-845




C(CH


3


)═NOH




H




H




CH




S







1-846




C(CH


3


)═NOH




H




Cl




CH




S







1-847




C(CH


3


)═NOH




Cl




H




CH




S







1-848




C(CH


3


)═NOH




H




NO


2






CH




S







1-849




C(CH


3


)═NOH




NO


2






H




CH




S







1-850




C(CH


3


)═NOMe




H




H




CH




S







1-851




C(CH


3


)═NOMe




H




Cl




CH




S







1-852




C(CH


3


)═NOMe




Cl




H




CH




S







1-853




C(CH


3


)═NOMe




H




NO


2






CH




S







1-854




C(CH


3


)═NOMe




NO


2






H




CH




S







1-855




F




H




H




CH




S







1-856




F




H




Cl




CH




S







1-857




F




Cl




H




CH




S







1-858




F




H




NO


2






CH




S







1-859




F




NO


2






H




CH




S







1-860




H




H




Cl




CH




O







1-861




H




Cl




H




CH




O







1-862




H




Cl




Cl




CH




O







1-863




H




H




Cl




CH




S







1-864




H




Cl




H




CH




S







1-865




H




Cl




Cl




CH




S







1-866




CH═NOH




H




Cl




CH




O







1-867




CH═NOH




Cl




H




CH




O






























TABLE 36











Compound




R


2






R


3






R


4






A




Y













1-868




CH═NOH




H




NO


2






CH




O







1-869




CH═NOH




NO


2






H




CH




O







1-870




CH═NOCH


3






H




H




CH




O







1-871




CH═NOCH


3






H




Cl




CH




O







1-872




CH═NOCH


3






Cl




H




CH




O







1-873




CH═NOCH


3






H




NO


2






CH




O







1-874




CH═NOCH


3






NO


2






H




CH




O







1-875




H




H




H




N




O







1-876




H




H




Cl




N




O







1-877




H




Cl




H




N




O







1-878




H




H




NO


2






N




O







1-879




H




NO


2






H




N




O







1-880




OH




H




H




N




O







1-881




OH




H




Cl




N




O







1-882




OH




Cl




H




N




O







1-883




OH




H




NO


2






N




O







1-884




OH




NO


2






H




N




O







1-885




OCH


3






H




H




N




O







1-886




OCH


3






H




Cl




N




O







1-887




OCH


3






Cl




H




N




O







1-888




OCH


3






H




NO


2






N




O







1-889




OCH


3






NO


2






H




N




O







1-890




OCH(CH


3


)CH


3






H




H




N




O







1-891




OCH(CH


3


)CH


3






H




Cl




N




O







1-892




OCH(CH


3


)CH


3






Cl




H




N




O






























TABLE 37











Compound




R


2






R


3






R


4






A




Y













1-893




OCH(CH


3


)CH


3






H




NO


2






N




O







1-894




OCH(CH


3


)CH


3






NO


2






H




N




O







1-895




OCH


2


C≡CH




H




H




N




O







1-896




OCH


2


C≡CH




H




Cl




N




O







1-897




OCH


2


C≡CH




Cl




H




N




O







1-898




OCH


2


C≡CH




H




NO


2






N




O







1-899




OCH


2


C≡CH




NO


2






H




N




O







1-900




OCH(CH


3


)C≡CH




H




H




N




O







1-901




OCH(CH


3


)C≡CH




H




Cl




N




O







1-902




OCH(CH


3


)C≡CH




Cl




H




N




O







1-903




OCH(CH


3


)C≡CH




H




NO


2






N




O







1-904




OCH(CH


3


)C≡CH




NO


2






H




N




O







1-905




OCH


2


CH═CH


2






H




H




N




O







1-906




OCH


2


CH═CH


2






H




Cl




N




O







1-907




OCH


2


CH═CH


2






Cl




H




N




O







1-908




OCH


2


CH═CH


2






H




NO


2






N




O







1-909




OCH


2


CH═CH


2






NO


2






H




N




O







1-910




OCH


2


CO


2


H




H




H




N




O







1-911




OCH


2


CO


2


H




H




Cl




N




O







1-912




OCH


2


CO


2


H




Cl




H




N




O







1-913




OCH


2


CO


2


H




H




NO


2






N




O







1-914




OCH


2


CO


2


H




NO


2






H




N




O







1-915




OCH


2


CO


2


Et




H




H




N




O







1-916




OCH


2


CO


2


Et




H




Cl




N




O







1-917




OCH


2


CO


2


Et




Cl




H




N




O






























TABLE 38











Compound




R


2






R


3






R


4






A




Y













1-918




OCH


2


CO


2


Et




H




NO


2






N




O







1-919




OCH


2


CO


2


Et




NO


2






H




N




O







1-920




OCH(CH


3


)CO


2


H




H




H




N




O







1-921




OCH(CH


3


)CO


2


H




H




Cl




N




O







1-922




OCH(CH


3


)CO


2


H




Cl




H




N




O







1-923




OCH(CH


3


)CO


2


H




H




NO


2






N




O







1-924




OCH(CH


3


)CO


2


H




NO


2






H




N




O







1-925




OCH(CH


3


)CO


2


Me




H




H




N




O







1-926




OCH(CH


3


)CO


2


Me




H




Cl




N




O







1-927




OCH(CH


3


)CO


2


Me




Cl




H




N




O







1-928




OCH(CH


3


)CO


2


Me




H




NO


2






N




O







1-929




OCH(CH


3


)CO


2


Me




NO


2






H




N




O







1-930




OCH(CH


3


)CO


2


Et




H




H




N




O







1-931




OCH(CH


3


)CO


2


Et




H




Cl




N




O







1-932




OCH(CH


3


)CO


2


Et




Cl




H




N




O







1-933




OCH(CH


3


)CO


2


Et




H




NO


2






N




O







1-934




OCH(CH


3


)CO


2


Et




NO


2






H




N




O







1-935




CO


2


H




H




H




N




O







1-936




CO


2


H




H




Cl




N




O







1-937




CO


2


H




Cl




H




N




O







1-938




CO


2


H




H




NO


2






N




O







1-939




CO


2


H




NO


2






H




N




O







1-940




CO


2


Me




H




H




N




O







1-941




CO


2


Me




H




Cl




N




O







1-942




CO


2


Me




Cl




H




N




O






























TABLE 39











Compound




R


2






R


3






R


4






A




Y













1-943




CO


2


Me




H




NO


2






N




O







1-944




CO


2


Me




NO


2






H




N




O







1-945




CO


2


Et




H




H




N




O







1-946




CO


2


Et




H




Cl




N




O







1-947




CO


2


Et




Cl




H




N




O







1-948




CO


2


Et




H




NO


2






N




O







1-949




CO


2


Et




NO


2






H




N




O







1-950




CO


2


CH(CH


3


)CO


2


Et




H




H




N




O







1-951




CO


2


CH(CH


3


)CO


2


Et




H




Cl




N




O







1-952




CO


2


CH(CH


3


)CO


2


Et




Cl




H




N




O







1-953




CO


2


CH(CH


3


)CO


2


Et




H




NO


2






N




O







1-954




CO


2


CH(CH


3


)CO


2


Et




NO


2






H




N




O







1-955




CO


2


C(CH


3


)


2


CO


2


Et




H




H




N




O







1-956




CO


2


C(CH


3


)


2


CO


2


Et




H




Cl




N




O







1-957




CO


2


C(CH


3


)


2


CO


2


Et




Cl




H




N




O







1-958




CO


2


C(CH


3


)


2


CO


2


Et




H




NO


2






N




O







1-959




CO


2


C(CH


3


)


2


CO


2


Et




NO


2






H




N




O







1-960




C(═O)H




H




H




N




O







1-961




C(═O)H




H




Cl




N




O







1-962




C(═O)H




Cl




H




N




O







1-963




C(═O)H




H




NO


2






N




O







1-964




C(═O)H




NO


2






H




N




O







1-965




CH═CHCO


2


Et




H




H




N




O







1-966




CH═CHCO


2


Et




H




Cl




N




O







1-967




CH═CHCO


2


Et




Cl




H




N




O






























TABLE 40











Compound




R


2






R


3






R


4






A




Y













1-968




CH═CHCO


2


Et




H




NO


2






N




O







1-969




CH═CHCO


2


Et




NO


2






H




N




O







1-970




CH═NOH




H




H




N




O







1-971




CH═NOH




H




Cl




N




O







1-972




CH═NOH




Cl




H




N




O







1-973




CH═NOH




H




NO


2






N




O







1-974




CH═NOH




NO


2






H




N




O







1-975




CH═NOCH


3






H




H




N




O







1-976




CH═NOCH


3






H




Cl




N




O







1-977




CH═NOCH


3






Cl




H




N




O







1-978




CH═NOCH


3






H




NO


2






N




O







1-979




CH═NOCH


3






NO


2






H




N




O







1-980




CH


2


CH


2


CO


2


Et




H




H




N




O







1-981




CH


2


CH


2


CO


2


Et




H




Cl




N




O







1-982




CH


2


CH


2


CO


2


Et




Cl




H




N




O







1-983




CH


2


CH


2


CO


2


Et




H




NO


2






N




O







1-984




CH


2


CH


2


CO


2


Et




NO


2






H




N




O







1-985




CH


2


CH(Cl)CO


2


Et




H




H




N




O







1-986




CH


2


CH(Cl)CO


2


Et




H




Cl




N




O







1-987




CH


2


CH(Cl)CO


2


Et




Cl




H




N




O







1-988




CH


2


CH(Cl)CO


2


Et




H




NO


2






N




O







1-989




CH


2


CH(Cl)CO


2


Et




NO


2






H




N




O







1-990




H




Cl




Cl




N




O







1-991




CF


3






H




Cl




N




O







1-992




CF


3






Cl




H




N




O










































TABLE 41











Compound




R


2






R


3






R


4






A




Y













1-2001




H




H




H




CH




CH







1-2002




Cl




H




H




CH




CH







1-2003




H




Cl




H




CH




CH







1-2004




H




H




Cl




CH




CH







1-2005




NO


2






H




H




CH




CH







1-2006




H




NO


2






H




CH




CH







1-2007




H




H




NO


2






CH




CH







1-2008




OH




H




H




CH




CH







1-2009




OCH


3






H




H




CH




CH







1-2010




OCH


2


CO


2


CH


3






H




H




CH




CH







1-2011




OCH


2


CO


2


C


2


H


5






H




H




CH




CH







1-2012




OCH(CH


3


)CO


2


CH


3






H




H




CH




CH







1-2013




OCH(CH


3


)CO


2


C


2


H


5






H




H




CH




CH







1-2014




OC(CH


3


)


2


CO


2


CH


3






H




H




CH




CH







1-2015




OC(CH


3


)


2


CO


2


C


2


H


5






H




H




CH




CH







1-2016




CO


2


H




H




H




CH




CH







1-2017




CO


2


CH


3






H




H




CH




CH







1-2018




CO


2


C


2


H


5






H




H




CH




CH







1-2019




CO


2


CH


2


CO


2


C


2


H


5






H




H




CH




CH







1-2020




CO


2


CH(CH


3


)CO


2


C


2


H


5






H




H




CH




CH







1-2021




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






H




H




CH




CH







1-2022




OH




Cl




H




CH




CH







1-2023




OCH


3






Cl




H




CH




CH







1-2024




OCH


2


CO


2


CH


3






Cl




H




CH




CH







1-2025




OCH


2


CO


2


C


2


H


5






Cl




H




CH




CH






























TABLE 42











Compound




R


2






R


3






R


4






A




Y













1-2026




OCH(CH


3


)CO


2


CH


3






Cl




H




CH




CH







1-2027




OCH(CH


3


)CO


2


C


2


H


5






Cl




H




CH




CH







1-2028




OC(CH


3


)


2


CO


2


CH


3






Cl




H




CH




CH







1-2029




OC(CH


3


)


2


CO


2


C


2


H


5






Cl




H




CH




CH







1-2030




CO


2


H




Cl




H




CH




CH







1-2031




CO


2


CH


3






Cl




H




CH




CH







1-2032




CO


2


C


2


H


5






Cl




H




CH




CH







1-2033




CO


2


CH


2


CO


2


C


2


H


5






Cl




H




CH




CH







1-2034




CO


2


CH(CH


3


)CO


2


C


2


H


5






Cl




H




CH




CH







1-2035




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






Cl




H




CH




CH







1-2036




OH




NO


2






H




CH




CH







1-2037




OCH


3






NO


2






H




CH




CH







1-2038




OCH


2


CO


2


CH


3






NO


2






H




CH




CH







1-2039




OCH


2


CO


2


C


2


H


5






NO


2






H




CH




CH







1-2040




OCH(CH


3


)CO


2


CH


3






NO


2






H




CH




CH







1-2041




OCH(CH


3


)CO


2


C


2


H


5






NO


2






H




CH




CH







1-2042




OC(CH


3


)


2


CO


2


CH


3






NO


2






H




CH




CH







1-2043




OC(CH


3


)


2


CO


2


C


2


H


5






NO


2






H




CH




CH







1-2044




CO


2


H




NO


2






H




CH




CH







1-2045




CO


2


CH


3






NO


2






H




CH




CH







1-2046




CO


2


C


2


H


5






NO


2






H




CH




CH







1-2047




CO


2


CH


2


CO


2


C


2


H


5






NO


2






H




CH




CH







1-2048




CO


2


CH(CH


3


)CO


2


C


2


H


5






NO


2






H




CH




CH







1-2049




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






NO


2






H




CH




CH







1-2050




Cl




H




Cl




CH




CH






























TABLE 43











Compound




R


2






R


3






R


4






A




Y













1-2051




H




H




H




N




CH







1-2052




Cl




H




H




N




CH







1-2053




H




Cl




H




N




CH







1-2054




H




H




Cl




N




CH







1-2055




NO


2






H




H




N




CH







1-2056




H




NO


2






H




N




CH







1-2057




H




H




NO


2






N




CH







1-2058




OH




H




H




N




CH







1-2059




OCH


3






H




H




N




CH







1-2060




OCH


2


CO


2


CH


3






H




H




N




CH







1-2061




OCH


2


CO


2


C


2


H


5






H




H




N




CH







1-2062




OCH(CH


3


)CO


2


CH


3






H




H




N




CH







1-2063




OCH(CH


3


)


2


CO


2


C


2


H


5






H




H




N




CH







1-2064




OC(CH


3


)


2


CO


2


CH


3






H




H




N




CH







1-2065




OC(CH


3


)


2


CO


2


C


2


H


5






H




H




N




CH







1-2066




CO


2


H




H




H




N




CH







1-2067




CO


2


CH


3






H




H




N




CH







1-2068




CO


2


C


2


H


5






H




H




N




CH







1-2069




CO


2


CH


2


CO


2


C


2


H


5






H




H




N




CH







1-2070




CO


2


CH(CH


3


)CO


2


C


2


H


5






H




H




N




CH







1-2071




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






H




H




N




CH







1-2072




OH




Cl




H




N




CH







1-2073




OCH


3






Cl




H




N




CH







1-2074




OCH


2


CO


2


CH


3






Cl




H




N




CH







1-2075




OCH


2


CO


2


C


2


H


5






Cl




H




N




CH






























TABLE 44











Compound




R


2






R


3






R


4






A




Y













1-2076




OCH(CH


3


)CO


2


CH


3






Cl




H




N




CH







1-2077




OCH(CH


3


)CO


2


C


2


H


5






Cl




H




N




CH







1-2078




OC(CH


3


)


2


CO


2


CH


3






Cl




H




N




CH







1-2079




OC(CH


3


)


2


CO


2


C


2


H


5






Cl




H




N




CH







1-2080




CO


2


H




Cl




H




N




CH







1-2081




CO


2


CH


3






Cl




H




N




CH







1-2082




CO


2


C


2


H


5






Cl




H




N




CH







1-2083




CO


2


CH


2


CO


2


C


2


H


5






Cl




H




N




CH







1-2084




CO


2


CH(CH


3


)CO


2


C


2


H


5






Cl




H




N




CH







1-2085




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






Cl




H




N




CH







1-2086




OH




NO


2






H




N




CH







1-2087




OCH


3






NO


2






H




N




CH







1-2088




OCH


2


CO


2


CH


3






NO


2






H




N




CH







1-2089




OCH


2


CO


2


C


2


H


5






NO


2






H




N




CH







1-2090




OCH(CH


3


)CO


2


CH


3






NO


2






H




N




CH







1-2091




OCH(CH


3


)CO


2


C


2


H


5






NO


2






H




N




CH







1-2092




OC(CH


3


)


2


CO


2


CH


3






NO


2






H




N




CH







1-2093




OC(CH


3


)


2


CO


2


C


2


H


5






NO


2






H




N




CH







1-2094




CO


2


H




NO


2






H




N




CH







1-2095




CO


2


CH


3






NO


2






H




N




CH







1-2096




CO


2


C


2


H


5






NO


2






H




N




CH







1-2097




CO


2


CH


2


CO


2


C


2


H


5






NO


2






H




N




CH







1-2098




CO


2


CH(CH


3


)CO


2


C


2


H


5






NO


2






H




N




CH







1-2099




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






NO


2






H




N




CH







1-2100




Cl




H




Cl




N




CH






























TABLE 45











Compound




R


2






R


3






R


4






A




Y













1-2101




H




H




H




CH




N







1-2102




Cl




H




H




CH




N







1-2103




H




Cl




H




CH




N







1-2104




H




H




Cl




CH




N







1-2105




NO


2






H




H




CH




N







1-2106




H




NO


2






H




CH




N







1-2107




H




H




NO


2






CH




N







1-2108




OH




H




H




CH




N







1-2109




OCH


3






H




H




CH




N







1-2110




OCH


2


CO


2


CH


3






H




H




CH




N







1-2111




OCH


2


CO


2


C


2


H


5






H




H




CH




N







1-2112




OCH(CH


3


)CO


2


CH


3






H




H




CH




N







1-2113




OCH(CH


3


)CO


2


C


2


H


5






H




H




CH




N







1-2114




OC(CH


3


)


2


CO


2


CH


3






H




H




CH




N







1-2115




OC(CH


3


)


2


CO


2


C


2


H


5






H




H




CH




N







1-2116




CO


2


H




H




H




CH




N







1-2117




CO


2


CH


3






H




H




CH




N







1-2118




CO


2


C


2


H


5






H




H




CH




N







1-2119




CO


2


CH


2


CO


2


C


2


H


5






H




H




CH




N







1-2120




CO


2


CH(CH


3


)CO


2


C


2


H


5






H




H




CH




N







1-2121




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






H




H




CH




N







1-2122




OH




Cl




H




CH




N







1-2123




OCH


3






Cl




H




CH




N







1-2124




OCH


2


CO


2


CH


3






Cl




H




CH




N







1-2125




OCH


2


CO


2


C


2


H


5






Cl




H




CH




N






























TABLE 46











Compound




R


2






R


3






R


4






A




Y













1-2126




OCH(CH


3


)CO


2


CH


3






Cl




H




CH




N







1-2127




OCH(CH


3


)CO


2


C


2


H


5






Cl




H




CH




N







1-2128




OC(CH


3


)


2


CO


2


CH


3






Cl




H




CH




N







1-2129




OC(CH


3


)


2


CO


2


C


2


H


5






Cl




H




CH




N







1-2130




CO


2


H




Cl




H




CH




N







1-2131




CO


2


CH


3






Cl




H




CH




N







1-2132




CO


2


C


2


H


5






Cl




H




CH




N







1-2133




CO


2


CH


2


CO


2


C


2


H


5






Cl




H




CH




N







1-2134




CO


2


CH(CH


3


)CO


2


C


2


H


5






Cl




H




CH




N







1-2135




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






Cl




H




CH




N







1-2136




OH




NO


2






H




CH




N







1-2137




OCH


3






NO


2






H




CH




N







1-2138




OCH


2


CO


2


CH


3






NO


2






H




CH




N







1-2139




OCH


2


CO


2


C


2


H


5






NO


2






H




CH




N







1-2140




OCH(CH


3


)CO


2


CH


3






NO


2






H




CH




N







1-2141




OCH(CH


3


)CO


2


C


2


H


5






NO


2






H




CH




N







1-2142




OC(CH


3


)


2


CO


2


CH


3






NO


2






H




CH




N







1-2143




OC(CH


3


)


2


CO


2


C


2


H


5






NO


2






H




CH




N







1-2144




CO


2


H




NO


2






H




CH




N







1-2145




CO


2


CH


3






NO


2






H




CH




N







1-2146




CO


2


C


2


H


5






NO


2






H




CH




N







1-2147




CO


2


CH


2


CO


2


C


2


H


5






NO


2






H




CH




N







1-2148




CO


2


CH(CH


3


)CO


2


C


2


H


5






NO


2






H




CH




N







1-2149




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






NO


2






H




CH




N







1-2150




Cl




H




Cl




CH




N






























TABLE 47











Compound




R


2






R


3






R


4






A




Y













1-2151




H




H




H




N




N







1-2152




Cl




H




H




N




N







1-2153




H




Cl




H




N




N







1-2154




H




H




Cl




N




N







1-2155




NO


2






H




H




N




N







1-2156




H




NO


2






H




N




N







1-2157




H




H




NO


2






N




N







1-2158




OH




H




H




N




N







1-2159




OCH


3






H




H




N




N







1-2160




OCH


2


CO


2


CH


3






H




H




N




N







1-2161




OCH


2


CO


2


C


2


H


5






H




H




N




N







1-2162




OCH(CH


3


)CO


2


CH


3






H




H




N




N







1-2163




OCH(CH


3


)CO


2


C


2


H


5






H




H




N




N







1-2164




OC(CH


3


)


2


CO


2


CH


3






H




H




N




N







1-2165




OC(CH


3


)


2


CO


2


C


2


H


5






H




H




N




N







1-2166




CO


2


H




H




H




N




N







1-2167




CO


2


CH


3






H




H




N




N







1-2168




CO


2


C


2


H


5






H




H




N




N







1-2169




CO


2


CH


2


CO


2


C


2


H


5






H




H




N




N







1-2170




CO


2


CH(CH


3


)CO


2


C


2


H


5






H




H




N




N







1-2171




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






H




H




N




N







1-2172




OH




Cl




H




N




N







1-2173




OCH


3






Cl




H




N




N







1-2174




OCH


2


CO


2


CH


3






Cl




H




N




N







1-2175




OCH


2


CO


2


C


2


H


5






Cl




H




N




N






























TABLE 48











Compound




R


2






R


3






R


4






A




Y













1-2176




OCH(CH


3


)CO


2


CH


3






Cl




H




N




N







1-2177




OCH(CH


3


)CO


2


C


2


H


5






Cl




H




N




N







1-2178




OC(CH


3


)


2


CO


2


CH


3






Cl




H




N




N







1-2179




OC(CH


3


)


2


CO


2


C


2


H


5






Cl




H




N




N







1-2180




CO


2


H




Cl




H




N




N







1-2181




CO


2


CH


3






Cl




H




N




N







1-2182




CO


2


C


2


H


5






Cl




H




N




N







1-2183




CO


2


CH


2


CO


2


C


2


H


5






Cl




H




N




N







1-2184




CO


2


CH(CH


3


)CO


2


C


2


H


5






Cl




H




N




N







1-2185




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






Cl




H




N




N







1-2186




OH




NO


2






H




N




N







1-2187




OCH


3






NO


2






H




N




N







1-2188




OCH


2


CO


2


CH


3






NO


2






H




N




N







1-2189




OCH


2


CO


2


C


2


H


5






NO


2






H




N




N







1-2190




OCH(CH


3


)CO


2


CH


3






NO


2






H




N




N







1-2191




OCH(CH


3


)CO


2


C


2


H


5






NO


2






H




N




N







1-2192




OC(CH


3


)


2


CO


2


CH


3






NO


2






H




N




N







1-2193




OC(CH


3


)


2


CO


2


C


2


H


5






NO


2






H




N




N







1-2194




CO


2


H




NO


2






H




N




N







1-2195




CO


2


CH


3






NO


2






H




N




N







1-2196




CO


2


C


2


H


5






NO


2






H




N




N







1-2197




CO


2


CH


2


CO


2


C


2


H


5






NO


2






H




N




N







1-2198




CO


2


CH(CH


3


)CO


2


C


2


H


5






NO


2






H




N




N







1-2199




CO


2


C(CH


3


)


2


CO


2


C


2


H


5






NO


2






H




N




N







1-2200




Cl




H




Cl




N




N










































TABLE 49











Compound




R


2






R


3






R


4






A




Y













2-1




H




H




H




CH




O







2-2




Cl




H




Cl




CH




O







2-3




H




H




H




CH




S







2-4




H




H




H




N




O







2-5




Cl




H




Cl




N




O







2-6




H




H




H




N




S







2-7




OCH


3






H




H




CH




O







2-8




OCH


3






H




H




N




O







2-9




NHCH


3






H




H




CH




O







2-10




NHCH


3






H




H




N




O







2-11




OCH


2


CH═CH


2






H




H




CH




O







2-12




OCH


2


CH═CH


2






H




H




N




O







2-13




CO


2


CH


2


CO


2


Et




H




H




CH




O







2-14




CO


2


CH


2


CO


2


Et




H




H




N




O







2-15




OCH


2


CO


2


C


2


H


5






H




H




CH




O







2-16




OCH


2


CO


2


C


2


H


5






H




H




N




O







2-17




OCH(CH


3


)CH═CH


2






H




H




CH




O







2-18




OCH(CH


3


)CH═CH


2






H




H




N




O







2-19




CO


2


CH(CH


3


)CO


2


Et




H




H




CH




O







2-20




CO


2


CH(CH


3


)CO


2


Et




H




H




N




O







2-21




OCH(CH


3


)CO


2


C


2


H


5






H




H




CH




O







2-22




OCH(CH


3


)CO


2


C


2


H


5






H




H




N




O







2-23




OCH(CH


3


)C≡CH




H




H




CH




O







2-24




OCH(CH


3


)C≡CH




H




H




N




O







2-25




OCH


2


C≡CH




H




H




CH




O






























TABLE 50











Compound




R


2






R


3






R


4






A




Y













2-26




OCH


2


C≡CH




H




H




N




O







2-27




OCH


3






NO


2






H




CH




O







2-28




OCH


3






NO


2






H




N




O







2-29




OCH


3






H




Cl




CH




O







2-30




OCH


3






H




Cl




N




O







2-31




CH


2


CO


2


CH


3






H




H




CH




O







2-32




CH


2


CO


2


CH


3






H




H




N




O







2-33




CH


2


CO


2


CH


3






NO


2






H




CH




O







2-34




CH


2


CO


2


CH


3






NO


2






H




N




O







2-35




CH


2


CO


2


CH


3






H




Cl




CH




O







2-36




CH


2


CO


2


CH


3






H




Cl




N




O







2-37




OCH(CH


3


)CO


2


C


2


H


5






NO


2






H




CH




O







2-38




OCH(CH


3


)CO


2


C


2


H


5






NO


2






H




N




O







2-39




OCH(CH


3


)CO


2


C


2


H


5






H




Cl




CH




O







2-40




OCH(CH


3


)CO


2


C


2


H


5






H




Cl




N




O







2-41




OCH


2


C≡CH




NO


2






H




CH




O







2-42




OCH


2


C≡CH




NO


2






H




N




O







2-43




OCH


2


C≡CH




H




Cl




CH




O







2-44




OCH


2


C≡CH




H




Cl




N




O







2-45




OCH(CH


3


)C≡CH




NO


2






H




N




O







2-46




OCH(CH


3


)C≡CH




NO


2






H




CH




O







2-47




OCH(CH


3


)C≡CH




H




Cl




N




O







2-48




OCH(CH


3


)C≡CH




H




Cl




CH




O







2-49




SCH(CH


3


)CO


2


C


2


H


5






NO


2






H




CH




O







2-50




SCH(CH


3


)CO


2


C


2


H


5






NO


2






H




N




O










































TABLE 51











Compound




R


2






R


3






R


4






A




Y













2-2001




H




H




H




CH




CH







2-2002




H




H




H




CH




N







2-2003




H




H




H




N




CH







2-2004




H




H




H




N




N







2-2005




OCH


3






H




H




CH




CH







2-2006




OCH


3






H




H




CH




N







2-2007




OCH


3






H




H




N




CH







2-2008




OCH


3






H




H




N




N







2-2009




CO


2


Et




H




H




CH




CH







2-2010




CO


2


Et




H




H




CH




N







2-2011




CO


2


Et




H




H




N




CH







2-2012




CO


2


Et




H




H




N




N







2-2013




OCH


2


CO


2


C


2


H


5






H




H




CH




CH







2-2014




OCH


2


CO


2


C


2


H


5






H




H




CH




N







2-2015




OCH


2


CO


2


C


2


H


5






H




H




N




CH







2-2016




OCH


2


CO


2


C


2


H


5






H




H




N




N







2-2017




OCH(CH


3


)CO


2


C


2


H


5






H




H




CH




CH







2-2018




OCH(CH


3


)CO


2


C


2


H


5






H




H




CH




N







2-2019




OCH(CH


3


)CO


2


C


2


H


5






H




H




N




CH







2-2020




OCH(CH


3


)CO


2


C


2


H


5






H




H




N




N







2-2021




OCH


2


C≡CH




H




H




CH




CH







2-2022




OCH


2


C≡CH




H




H




CH




N







2-2023




OCH


2


C≡CH




H




H




N




CH







2-2024




OCH


2


C≡CH




H




H




N




N







2-2025




OCH(CH


3


)C≡CH




H




H




N




N










































TABLE 52











Compound




R


2






R


3






R


4






A




Y













3-1




H




H




H




CH




O







3-2




Cl




H




Cl




CH




O







3-3




H




H




H




CH




S







3-4




H




H




H




N




O







3-5




Cl




H




Cl




N




O







3-6




H




H




H




N




S







3-7




OCH


3






H




H




CH




O







3-8




OCH


3






H




H




N




O







3-9




NHCH


3






H




H




CH




O







3-10




NHCH


3






H




H




N




O







3-11




OCH


2


CH═CH


2






H




H




CH




O







3-12




OCH


2


CH═CH


2






H




H




N




O







3-13




CO


2


CH


2


CO


2


Et




H




H




CH




O







3-14




CO


2


CH


2


CO


2


Et




H




H




N




O







3-15




OCH


2


CO


2


C


2


H


5






H




H




CH




O







3-16




OCH


2


CO


2


C


2


H


5






H




H




N




O







3-17




OCH(CH


3


)CH═CH


2






H




H




CH




O







3-18




OCH(CH


3


)CH═CH


2






H




H




N




O







3-19




CO


2


CH(CH


3


)CO


2


Et




H




H




CH




O







3-20




CO


2


CH(CH


3


)CO


2


Et




H




H




N




O







3-21




OCH(CH


3


)CO


2


C


2


H


5






H




H




CH




O







3-22




OCH(CH


3


)CO


2


C


2


H


5






H




H




N




O







3-23




OCH(CH


3


)C≡CH




H




H




CH




O







3-24




OCH(CH


3


)C≡CH




H




H




N




O







3-25




OCH


2


C≡CH




H




H




CH




O






























TABLE 53











Compound




R


2






R


3






R


4






A




Y













3-26




OCH


2


C≡CH




H




H




N




O







3-27




OCH


3






NO


2






H




CH




O







3-28




OCH


3






NO


2






H




N




O







3-29




OCH


3






H




Cl




CH




O







3-30




OCH


3






H




Cl




N




O







3-31




CH


2


CO


2


CH


3






H




H




CH




O







3-32




CH


2


CO


2


CH


3






H




H




N




O







3-33




CH


2


CO


2


CH


3






NO


2






H




CH




O







3-34




CH


2


CO


2


CH


3






NO


2






H




N




O







3-35




CH


2


CO


2


CH


3






H




Cl




CH




O







3-36




CH


2


CO


2


CH


3






H




Cl




N




O







3-37




OCH(CH


3


)CO


2


C


2


H


5






NO


2






H




CH




O







3-38




OCH(CH


3


)CO


2


C


2


H


5






NO


2






H




N




O







3-39




OCH(CH


3


)CO


2


C


2


H


5






H




Cl




CH




O







3-40




OCH(CH


3


)CO


2


C


2


H


5






H




Cl




N




O







3-41




OCH


2


C≡CH




NO


2






H




CH




O







3-42




OCH


2


C≡CH




NO


2






H




N




O







3-43




OCH


2


C≡CH




H




Cl




CH




O







3-44




OCH


2


C≡CH




H




Cl




N




O







3-45




OCH(CH


3


)C≡CH




NO


2






H




N




O







3-46




OCH(CH


3


)C≡CH




NO


2






H




CH




O







3-47




OCH(CH


3


)C≡CH




H




Cl




N




O







3-48




OCH(CH


3


)C≡CH




H




Cl




CH




O







3-49




SCH(CH


3


)CO


2


C


2


H


5






NO


2






H




CH




O







3-50




SCH(CH


3


)CO


2


C


2


H


5






NO


2






H




N




O










































TABLE 54











Compound




R


2






R


3






R


4






A




Y













3-2001




H




H




H




CH




CH







3-2002




H




H




H




CH




N







3-2003




H




H




H




N




CH







3-2004




H




H




H




N




N







3-2005




OCH


3






H




H




CH




CH







3-2006




OCH


3






H




H




CH




N







3-2007




OCH


3






H




H




N




CH







3-2008




OCH


3






H




H




N




N







3-2009




CO


2


Et




H




H




CH




CH







3-2010




CO


2


Et




H




H




CH




N







3-2011




CO


2


Et




H




H




N




CH







3-2012




CO


2


Et




H




H




N




N







3-2013




OCH


2


CO


2


C


2


H


5






H




H




CH




CH







3-2014




OCH


2


CO


2


C


2


H


5






H




H




CH




N







3-2015




OCH


2


CO


2


C


2


H


5






H




H




N




CH







3-2016




OCH


2


CO


2


C


2


H


5






H




H




N




N







3-2017




OCH(CH


3


)CO


2


C


2


H


5






H




H




CH




CH







3-2018




OCH(CH


3


)CO


2


C


2


H


5






H




H




CH




N







3-2019




OCH(CH


3


)CO


2


C


2


H


5






H




H




N




CH







3-2020




OCH(CH


3


)CO


2


C


2


H


5






H




H




N




N







3-2021




OCH


2


C≡CH




H




H




CH




CH







3-2022




OCH


2


C≡CH




H




H




CH




N







3-2023




OCH


2


C≡CH




H




H




N




CH







3-2024




OCH


2


C≡CH




H




H




N




N







3-2025




OCH(CH


3


)C≡CH




H




H




N




N















For some of the present compounds, melting points or


1


H-NMR data as their physical properties are shown below.




The Present Compound 1-4




m.p.: 132.1° C.




The Present Compound 1-11






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.20 (3H, t, J=7.14 Hz), 1.44 (3H, d, J=6.92 Hz), 3.56 (3H, m), 4.06-4.20 (4H, m), 6.38 (1H, s), 6.42 (1H, d, J=2.33 Hz), 6.67 (1H, dd, J=8.87 Hz, 2.33 Hz), 7.32 (1H, d, J=8.87 Hz), 7.72 (1H, s).




The Present Compound 1-76






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.60 (3H, s), 6.40 (1H, s), 7.39 (1H, d, J=1.52 Hz), 7.51 (1H, d, J=1.52 Hz), 7.91 (1H, s).




The Present Compound 1-77






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.59 (3H, s), 6.40 (1H, s), 7.61 (1H, s), 7.69 (1H, s), 7.84 (1H, s).




The Present Compound 1-80






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 3.58-3.60 (3H, m), 5.47 (1H, s), 6.40 (1H, s), 6.92 (1H, s), 7.56 (1H, s), 7.80 (1H, s).




The Present Compound 1-82






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.60-3.61 (3H, m), 6.41 (1H, s), 7.02 (1H, s), 8.05 (1H, s), 8.35 (1H, s), 10.46 (1H, s).




The Present Compound 1-83






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.59 (3H, s), 3.80 (3H, s), 6.39 (1H, s), 6.64 (1H, d, J=2.19 Hz), 7.00 (1H, d, J=2.19 Hz), 7.85 (1H, s).




The Present Compound 1-84






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 3.60-3.61 (3H, m), 3.91 (3H, s), 6.41 (1H, s), 6.75 (1H, s), 7.61 (1H, s), 7.80 (1H, s).




The Present Compound 1-86






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.61 (3H, m), 3.95 (3H, s), 6.42 (1H, s), 6.89 (1H, s), 8.00 (1H, s), 8.09 (1H, s).




The Present Compound 1-128






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.22 (3H, t, J=7.08 Hz), 1.60 (3H, d, J=6.76 Hz), 3.58 (3H, m), 4.15-4.24 (2H, m), 4.71 (1H, q, J=6.78 Hz), 6.39 (1H, s), 6.66 (1H, d, J=2.33 Hz), 7.03 (1H, d, J=2.33 Hz), 7.86 (1H, s).




The Present Compound 1-129






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.20 (3H, t, J=7.17 Hz), 1.66 (3H, d, J=6.76 Hz), 3.57 (3H, s), 4.18 (2H, q, J=7.10 Hz), 4.72 (1H, q, J=6.85 Hz), 6.38 (1H, s), 6.83 (1H, s), 7.60 (1H, s), 7.80 (1H, s).




The Present Compound 1-131






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.20 (3H, t, J=7.20 Hz), 1.67 (3H, d, J=6.90 Hz), 3.60 (3H, m), 4.18 (2H, q, J=7.09 Hz), 4.80 (1H, q, J=6.80 Hz), 6.40 (1H, s), 6.92 (1H, s), 8.02 (1H, s), 8.09 (1H, s).




The Present Compound 1-246






1


H-NMR (250 MHz, CDCl


3


, TMS, δ (ppm)): 1.13 (3H, t, J=7.07 Hz), 1.55 (3H, d, J=7.25 Hz), 3.61-3.62 (3H, m), 3.96 (1H, q, J=7.14 Hz), 4.08-4.15 (2H, m), 6.42 (1H, s), 8.10 (1H, s), 8.28 (1H, s).




The Present Compound 1-285






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.61 (3H, m), 6.42 (1H, s), 7.72 (1H, s), 7.73 (1H, s), 7.98 (1H, s).




The Present Compound 1-289






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.61-3.62 (3H, m), 6.43 (1H, s), 7.81 (1H, d, J=1.26 Hz), 7.93 (1H, d, J=1.44 Hz), 8.02 (1H, s), 10.00 (1H, s).




The Present Compound 1-304






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.60 (3H, s), 3.94 (3H, s), 6.41 (1H, s), 7.97 (1H, s), 7.98 (1H, d, J=1.35 Hz), 8.09 (1H,d, J=1.35 Hz).




The Present Compound 1-305






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.59 (3H, m), 3.93 (3H, s), 6.40 (1H, s), 7.67 (1H, s), 7.87 (1H, s), 7.89 (1H, s).




The Present Compound 1-358






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 2.40 (3H, s), 3.59 (3H, m), 6.40 (1H, s), 7.01 (1H, s), 7.19 (1H, s), 7.85 (1H, s).




The Present Compound 1-361






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 2.67 (3H, s), 3.61 (3H, m), 6.42 (1H, s), 7.27 (1H, s), 8.03 (1H, s), 8.27 (1H, s).




The Present Compound 1-378




m.p.: 208.2° C.




The Present Compound 1-861




m.p.: 135.9° C.




The Present Compound 1-864




m.p.: 183.8° C.




The Present Compound 1-871




m.p.: 193.2° C.




The Present Compound 1-882






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.59-3.61 (3H, m), 6.42 (1H, s), 6.98 (1H, s), 7.85 (1H, s).




The Present Compound 1-887






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 3.61 (3H, s), 3.96 (1H, s), 6.44 (1H, s), 6.91 (1H, s), 7.94 (1H, s).




The Present Compound 1-892






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.41 (6H, d, J=6.3 Hz), 3.60 (3H, d, J=1.1 Hz), 4.56-4.68 (1H, m), 6.43 (1H, s), 6.91 (1H, s), 7.91 (1H, s).




The Present Compound 1-932






1


H-NMR (300 MHz, CDCl


3


, TMS, δ (ppm)): 1.19 (3H, t, J=7.1 Hz), 1.73 (3H, d, J=7.0), 3.59-3.61 (3H, m), 4.14-4.23 (2H, m), 4.81 (1H, q, J=7.1 Hz), 6.42 (1H, s), 6.87 (1H, s), 7.96 (1H, s).




The following are Formulation Examples in which the present compounds are indicated by their compound numbers in Tables 1 to 54 and parts are by weight.




Formulation Example 1




Fifty parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2-2025, 3-1 to 3-50 and 3-2001 to 3-2025, 3 parts of calcium lignin sulfonate, 2 parts of sodium lauryl sulfate, and 45 parts of synthetic hydrated silicon oxide are well pulverized and mixed to give a wettable powder for each compound.




Formulation Example 2




Ten parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025, 3-1 to 3-50 and 3-2001 to 3-2025, 14 parts of polyoxyethylene styryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate, 35 parts of xylene, and 35 parts of cyclohexanone are well mixed to an emulsifiable concentrate for each compound.




Formulation Example 3




Two parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025, 3-1 to 3-50 and 3-2001 to 3-2025, 2 parts of synthetic hydrated silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite, and 64 parts of kaolin clay are well pulverized and mixed, and the mixture is well kneaded with water, followed by granulation and drying, to give a granule for each compound.




Formulation Example 4




Twenty-five parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025, 3-1 to 3-50 and 3-2001 to 3-2025, 50 parts of 10% aqueous polyvinyl alcohol solution, and 25 parts of water are mixed and pulverized until the mean particle size reaches 5 μm or smaller to give a flowable for each compound.




Formulation Example 5




Five parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2-2025, 3-1 to 3-50 and 3-2001 to 3-2025 is added to 40 parts of 10% aqueous polyvinyl alcohol solution, and the mixture is emulsified by dispersion with a homogenizer until the mean particle size reaches 10 μm or smaller, followed by addition of 55 parts of water, to give a concentrated emulsion for each compound




The following are Test Examples for demonstrating that the present compounds are useful as active ingredients of herbicides. In Test Examples, the present compounds are designated by their compound numbers in Tables 1 to 54.




Test Example 1




Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, seeded with velvetleaf (Abutilon theophrasti), and kept in a greenhouse for 14 days. After that, according to Formulation Example 2, compound 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-871, 1-877, 1-892, 1-2068, 2-4 or 2-2011 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water containing a spreading agent and then uniformly sprayed over the foliage of the plants with a sprayer at a ratio of 1000 liters per hectare. The pots were further kept in the greenhouse for 8 days and examined for herbicidal activity. As a result, it was found that compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-871, 1-877, 1-892, 1-2068, 2-4 and 2-2011 completely inhibited the growth of velvetleaf at a dosage of 2000 g/ha.




Test Example 2




Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, seeded with velvetleaf (


Abutilon theophrasti


), and kept in a greenhouse for 14 days. After that, according to Formulation Example 2, compound 2-2001 or 3-2001 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water containing a spreading agent and then uniformly sprayed over the foliage of the plants with a sprayer at a ratio of 1000 liters per hectare. The pots were further kept in the greenhouse for 5 days and examined for herbicidal activity. As a result, it was found that compounds .2-2001 and 3-2001 completely killed velvetleaf at a dosage of 8000 g/ha.




Test Example 3




Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil and seeded with velvetleaf (


Abutilon theophrasti


). According to Formulation Example 2, compound 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-877 or 1-892 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water and then uniformly sprayed over the surface of the soil in the pots with a sprayer at a ratio of 1000 liters per hectare. The pots were kept in a greenhouse for 9 days and examined for herbicidal activity. As a result, it was found that compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-877 and 1-892 completely inhibited the germination of velvetleaf at a dosage of 2000 g/ha.




Test Example 4




Cylindrical plastic pots of 9 cm in diameter and 11 cm of depth were filled with soil, seeded with barnyardgrass (


Echinochloa oryzicola


), flooded into a paddy field, and kept in a greenhouse for 12 days. According to Formulation Example 2, compound 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-864, 1-877 or 1-892 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water and then applied on the water surface in the pots at a ratio of 50 liters per are. The pots were further kept in the greenhouse for 9 days and examined for herbicidal activity. As a result, it was found that compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-864, 1-877 and 1-892 completely inhibited the growth of barnyardgrass at a dosage of 1000 g/ha.




Industrial applicability




The condensed heterocyclic compounds of the present invention are useful as active ingredients of herbicides because of their excellent herbicidal activity.



Claims
  • 1. A condensed heterocyclic compound of general formula I wherein T is carbon and the bond between T and A is a double bond, the bond between A and Y is a single bond, and Y is oxygen;A is C—R141 wherein R141 is hydrogen; R1 is hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, hydroxymethyl, nitro, or cyano; R2 is hydrogen, halogen, C1-C11, alkyl C1-C11 haloalkyl, hydroxymethyl, nitro, cyano, —N(R9)R19, —OR11, —SR12, —SO2R13, —COX, —COOR14, —CON(R15)R16, —COOR17, —C(R26)═NOR19, —C(R27)═C(R21)R22, or —OH(R23)—CH(R24)R25; R3 is hydrogen, halogen, C1-C11 alkyl, C1-C11 haloalkyl, hydroxymethyl, nitro, cyano, —N(R59)R60, —OR61, —SR62, —SO2R63, —COX, —COOR64, —CON(R65)R66, —COR67, —C(R76)═CR69, —C(R77)═C(R71)R72, or —CH(R73)—CH(R74)R75; R4 is hydrogen, halogen, C1-C3, alkyl, C1-C3 haloalkyl, hydroxymethyl, nitro, or cyano;  wherein X is chlorine or bromine; R9 and R59 are independently hydrogen, C1-C5 alkyl, (C1-C5 alkyl)carbonyl, or (C1-C5 alkoxy) carbonyl; R10, R11, and R12 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, (C1-C5 alkyl)carbonyl, (C1-C5 haloalkyl)carbonyl, (C3-C10 cycloalkyl)carbonyl, (C1-C5 alkyl)carbonyl C1-C5 alkyl, (C1-C5 haloalkyl)carbonyl C1-C5 alkyl, hydroxy C1-C5 alkyl, C1-C5 alkoxy C1-C5 alkyl, C1-C5 alkylthio C1-C5 alkyl, (C1-C5 alkoxy)carbonyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —C(R43) (R44)—C(═O)ON(R45)R46, —C(R47) (R48)—CON(R49)R50, —CH2—C(R56)═N—OR55, —CHMe—C(R58)═NOR57, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, carboxy(C1-C5 alkyl)carbonyl, (C1-C10 alkoxy)carbonyl(C1-C5 alkyl)carbonyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkyl)carbonyl, C1-C5 alkylsulfonyl, C1-C5 haloalkylsulfonyl, —SO2N(R51)R52, —CON(R53)R54, optionally substituted benzyl, or optionally substituted phenyl; R60, R61, and R62 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, (C1-C5 alkyl)carbonyl, (C1-C5 haloalkyl)carbonyl, (C3-C10 cycloalkyl)carbonyl, (C1-C5 alkyl)carbonyl C1-C5 alkyl, (C1-C5 haloalkyl)carbonyl C1-C5 alkyl, hydroxy C1-C5 alkyl, C1-C5 alkoxy C1-C5 alkyl, C1-C5 alkylthio C1-C5 alkyl, C1-C6 alkoxy)carbonyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —C(R163)(R164)—C(═O)ON(R165)R166, —C(R167)(R168)—CON(R169)R170, —CH2—C(═NOR175)R176, —CHMe—C(═NOR177)R178, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, carboxy(C1-C5 alkyl)carbonyl, (C1-C10 alkoxy)carbonyl(C1-C5 alkyl)carbonyl, (C1-C10 haloalkoxy)carbonyl(C1-C5 alkyl)carbonyl, C1-C5 alkylsulfonyl, C1-C5 haloalkylsulfonyl, —SO2N(R171)R172, —CON(R173)R174, optionally substituted benzyl, or optionally substituted phenyl;  wherein R43, R44, R163, and R164 are independently hydrogen, halogen, C1-C5 alkyl, or C1-C5 haloalkyl; R45, R46, R165, and R166 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R45 and R46 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated rind, or R165 and R166 may be combined at their ends to form together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; R47, R48, R167, and R168 are independently hydrogen, halogen, C1-C5 alkyl, or C1-C5 haloalkyl; R49, R50, R169, and R170 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R49 and R50 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R169 and R170 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; P51, R52, R171 and R172 are independently hydrogen, C1-C5 alkyl C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl; or C3-C6 alkynyl; or R51 and R52 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R171 and 172 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R53, R54, R173, and R174 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkynyl, or C3-C6 alkynyl; or R53 and R54 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R173 and R174 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R55, R57, R175, and R177 are independently hydrogen or C1-C3 alkyl; R56, R58, R176, and R178 are independently hydrogen, C1-C5 alkyl, (C1-C5 alkoxy)carbonyl, (C1-C5 haloalkoxy)carbonyl, (C3-C5 cycloalkoxy)carbonyl, (C3-C5 alkenoxy)carbonyl, or (C3-C5 alkynoxy)carbonyl; R13 is hydroxy, chlorine, C1-C10 alkyl, C1-C10 haloalkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl, C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —N(R79)R80, or —OR81; R63 hydroxy, chlorine, C1-C10 alkyl, C1-C10 haloalkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl, C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —N(R179)R180, or —OR181;  wherein R79 and R179 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl, C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R80 and R180 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R79 and R80 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R179 and R180 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; and R81 and R181 are independently C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R14 is hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy) carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, —N(R82)R83, optionally substituted benzyl, or optionally substituted phenyl; R64 is hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, —N(R182)R183, optionally substituted benzyl, or optionally substituted phenyl; wherein R82 and R182 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R83 sand R183 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R82 and R83 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R182 and R183 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R15 and R65 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, cyano C1-C6 alkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, optionally substituted benzyl, or optionally substituted phenyl; R16 and R56 are independently hydrogen, C1-C10 alkyl, or C1-C10 haloalkyl; or R15 and R16 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R65 and R66 may be, combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R17, R26, R27, R67, R76, and R77 are independently hydrogen, cyano, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, (C1-C6 alkoxy)carbonyl, or (C1-C6 alkoxy)carbonylmethyl; R19 and R69 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R21 and R71 are independently hydrogen, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; R22 and R25 are independently carboxy, (C1-C10 alkoxy)carbonyl, (C1-C10 haloalkoxy)carbonyl, (C3-C10 cyrloalkoxy)carbonyl (C3-C10 halocycloalkoxy)carbonyl, carboxy(C1-C5 alkoxy)carbonyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkenoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkynoxy)carbonyl (C1-C5 alkoxy)carbonyl, —CON(R84)R85, or —C(═O)ON(R86)R87; R72 and R75 are independently carboxy, (C1-C10 alkoxy)carbonyl, (C1-C10 haloalkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl, (C3-C10 halocycloalkoxy)carbonyl, carboxy(C1-C5 alkoxy)carbonyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy) carbonyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkenoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkynoxy)carbonyl (C1-C5 alkoxy carbonyl, —CON(R184)R185, or —C(═O)ON(R186)R187;  wherein R84 and R184 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, (C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R85 and R185 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R84 and R85 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R184 and R185 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R86 and R186 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R87 and R187 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R86 and R87 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; or R186 and R187 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; R23, R24, R73, and R74 are independently hydrogen, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; and Q is any one group of Q14, Q15, or Q17 of the general formula:  wherein: in Q14, E25 is hydrogen, C1-C3 alkyl, or halogen; E26 is C1-C3 alkyl optionally substituted with halogen; E27 is hydrogen, amino, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, or optionally substituted benzyl; and D7 is oxygen or sulfur; in Q15, E28 is C1-C3 alkyl optionally substituted with halogen; E29 is hydrogen, amino, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, or optionally substituted benzyl; and Do is oxygen or sulfur; and in Q17, E32 is C1-C3 alkyl optionally substituted with halogen; E33 is hydrogen, halogen, amino, C1-C3 alkyl optionally substituted with halogen, C1-C3 alkoxy optionally substituted with halogen, or C1-C3 alkylthio optionally substituted with halogen; and E43 is hydrogen or C1-C3 alkyl optionally substituted with halogen.
  • 2. The condensed heterocyclic compound according to claim 1, wherein Q is Q14.
  • 3. The condensed heterocyclic compound according to claim 1, wherein Q is Q15.
  • 4. The condensed heterocyclic compound according to claim 1, wherein Q is Q1, of which E1 and E2 are combined at their ends to form C2-C6 alkylene (which alkylene may optionally be substituted with methyl or halogen) or C2-C5 alkenylene (which alkenylene may optionally be substituted with methyl or halogen); orQ is Q2, of which E3 and E4 are combined at their ends to form C2-C5 alkylene (which alkylene may optionally be substituted with methyl or halogen) or C2-C5 alkenylene (which alkenylene may optionally be substituted with methyl or halogen), and D1 and Z1 are as defined above; or Q is Q4, of which E6 is C1-C6 alkyl optionally substituted with halogen and E7 is C1-C6 alkyl optionally substituted with halogen; or Q is Q4, of which E6 and E7 are combined at their ends to form C2-C5 alkylene (which alkylene may optionally be substituted with methyl or halogen) or C2-C5 alkenylene (which alkenylene may optionally be substituted with methyl or halogen); or Q is Q6, of which E44 is chlorine or bromine, E10 is C1-C6 alkyl optionally substituted with halogen, and E11 is C1-C6 alkyl optionally substituted with halogen; or Q is Q6, of which E44 is chlorine or bromine, and E10 and E11 are combined at their ends to form C2-C5 alkylene (which alkylene may optionally be substituted with methyl or halogen) or C2-C5 alkenylene (which alkylene may optionally be substituted with methyl or halogen).
  • 5. The condensed heterocyclic compound according to claim 1, wherein Q is Q1, of which E1 and E2 are combined at their ends to form tetramethylene (which tetramethylene may optionally be substituted with methyl or halogen); orQ is Q2, of which E3 and E4 are combined at their ends to form tetramethylene (which tetramethylene may optionally be substituted with methyl or halogen), D1 is oxygen, and Z1 is nitrogen; or Q is Q4, of which E6 is methyl substituted with fluorine, or ethyl substituted with fluorine, and E7 is methyl or ethyl; or Q is Q4, of which E6 and E7 are combined at their ends to form tetramethylene (which tetramethylene may optionally be substituted with methyl or halogen); or Q is Q6, of which E44 is chlorine or bromine, E10 is methyl substituted with fluorine, or ethyl substituted with fluorine, and E11 is methyl or ethyl; or Q is Q6, of which E10 and E11 are combined at their ends to form tetramethylene (which tetramethylene may optionally be substituted with methyl or halogen).
  • 6. The condensed heterocyclic compound according to claim 1, wherein Q is Q17.
  • 7. The condensed heterocyclic compound according to claim 1, wherein Q is Q14, of which E25 is hydrogen, E26 is C1-C3 alkyl optionally substituted with halogen, E27 is C1-C3 alkyl, and D7 is oxygen.
  • 8. The condensed heterocyclic compound according to claim 1, wherein Q is Q14, of which E25 is hydrogen, E26 is methyl substituted with fluorine, or ethyl substituted with fluorine, E27 is methyl or ethyl, and D7 is oxygen.
  • 9. The condensed heterocyclic compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, or 8 wherein A s nitrogen, CH, CCH3, CCl, or CBr.
  • 10. The condensed heterocyclic compound according to claim 1, wherein R1 is hydrogen or halogen.
  • 11. The condensed heterocyclic compound according to claim 1, wherein T is nitrogen.
  • 12. The condensed heterocyclic compound according to claim 1, wherein R2 is hydrogen, halogen, C1-C11 alkyl, nitro, cyano, —N(R9)R10, —OR11, —SR12, COOR14, —CON(R15)R16, —COR17, —C(R26)═NOR19, —C(R27)═C(R21)R22, or —CH(R23)—CH(R24)R25.
  • 13. The condensed heterocyclic compound according to claim 1, wherein R3 is hydrogen, halogen, or nitro.
  • 14. The condensed heterocyclic compound according to claim 1, wherein R4 is hydrogen or halogen.
  • 15. The condensed heterocyclic compound according to claim 1, wherein T is carbon, A is CH, Y is oxygen, R1 is hydrogen, Q is Q14, E25 is hydrogen, E26 is trifluoromethyl, and E27 is methyl.
  • 16. A herbicidal composition comprising a condensed heterocyclic compound according to claim 1, and an inert carrier or diluent.
  • 17. A method for controlling weeds, which comprises applying an effective amount of a condensed heterocyclic compound according to claim 1, to weeds or to a place where weeds are growing or will grow.
Priority Claims (3)
Number Date Country Kind
10-257237 Sep 1998 JP
11-004373 Jan 1999 JP
11-143300 May 1999 JP
Parent Case Info

This application is the national phase under 35 U.S.C. § 371 of PCT International Application No. PCT/JP99/04758, which has an International filing date of Sep. 2, 1999, which designated the, United States of America.

PCT Information
Filing Document Filing Date Country Kind
PCT/JP99/04758 WO 00
Publishing Document Publishing Date Country Kind
WO00/15633 3/23/2000 WO A
Foreign Referenced Citations (8)
Number Date Country
A188259 Jul 1986 EP
0476679 Mar 1992 EP
A476697 Mar 1992 EP
A563916 Oct 1993 EP
A9712884 Apr 1997 WO
A9712886 Apr 1997 WO
A9838188 Aug 1998 WO
WO 2002000653 Feb 2002 WO
Non-Patent Literature Citations (5)
Entry
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Gilchrist et al., JCS Chemical Communications, pp. 1519-1520 (1971).
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