Patent Application
20230085307
The present invention relates to a novel pyridazinone compound or a salt thereof, and an agricultural chemical (in particular, a herbicide) containing the compound as an active ingredient.
For example, Patent Documents 1 and 2 disclose a certain type of pyridazinone compound. However, the pyridazinone compound according to the present invention has not been disclosed at all.
An object of the present invention is to provide a chemical substance which reliably exhibits effects on various weeds even when applied in a small amount, which is less likely to cause problems (e.g., land pollution and adverse effects on succeeding crops), and which exhibits high safety and is useful as an active ingredient of a herbicide.
The present inventors have conducted extensive studies for solving the aforementioned problems, and as a result have found that a novel pyridazinone compound of Formula (1) described below is a very useful compound having excellent herbicidal activity as a herbicide and high safety against target crops, and exhibiting almost no adverse effects on non-target living organisms (e.g., such as mammals, fishes, beneficial insects, and natural enemies). The present invention has been accomplished on the basis of this finding.
Accordingly, the present invention is directed to the following [1] to [152].
[1]
A pyridazinone compound of the following Formula (1) or a salt thereof:
[wherein W1 is an oxygen atom or a sulfur atom;
X is an oxygen atom or a sulfur atom;
Z1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, (C3-6) cycloalkyl substituted with R44, phenyl, phenyl substituted with (Z4)p5c, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-10, Q-11, Q-12, Q-13, —NR15R16, —OR35, —S(O)r1R36, —CN, —NO2, —C(O)OH, —C(═W3)R20, or —N═C(C6H5)2, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
G is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R4, —C(═W4)R5, or —S(O)2R6;
R1 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, or C1-6 alkyl substituted with R34;
R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl, or —NR30R31;
R3 is D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-11, D-12, D-13, D-14, D-15, D-16, D-17, D-18, D-19, D-20, D-21, D-22, D-23, D-24, D-25, D-26, D-27, D-28, D-29, D-30, D-31, D-32, D-33, D-34, D-35, D-36, D-37, D-38, D-39, D-40, D-41, D-42, D-43, D-44, D-45, D-46, D-47, D-48, D-49, D-50, D-51, D-52, D-53, D-54, D-55, or D-56;
D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-11, D-12, D-13, D-14, D-15, D-16, D-17, D-18, D-19, D-20, D-21, D-22, D-23, D-24, D-25, D-26, D-27, D-28, D-29, D-30, D-31, D-32, D-33, D-34, D-35, D-36, D-37, D-38, D-39, D-40, D-41, D-42, D-43, D-44, D-45, D-46, D-47, D-48, D-49, D-50, D-51, D-52, D-53, D-54, D-55, and D-56 are respectively the following structures:
Y1 is substituted on the aromatic ring of each of D-1 to D-56, and Y3 is substituted on the aliphatic ring of D-19, D-20, D-21, D-22, D-24, D-29, D-30, D-31, or D-32;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-6 haloalkenyl, C2-6 haloalkynyl, (C1-6) alkyl substituted with R10, C3-6 cycloalkyl substituted with R44, —OR11, —S(O)r2R38, —NR8R9, —CN, —NO2, —C(O)OH, —C(═W2)R13, phenyl, phenyl substituted with (Z4)p5c, tri(C1-6 alkyl)silyl, Q-6, Q-7, Q-10, Q-11, Q-12, or Q-13, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R4 is a halogen atom, —CN, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, —OR24, —S(O)r4R54, —C(O)R23, phenyl, phenyl substituted with (Z4)p5c, U-1, U-2, U-3, U-4, U-5, U-9, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, U-34, U-35, Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, or Q-36;
R5 is C1-6 alkyl, (C1-6) alkyl substituted with R26, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkoxy, —OR58, —SR59, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, —NR56R57, U-1, U-2, U-3, U-4, U-5, U-6, U-7, U-8, U-9, U-10, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29U-30, U-31, U-32, U-33, U-34, U-35, Q-1, Q-2, Q-3, Q-4, Q-5, Q-7, Q-8, Q-9, Q-10, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, Q-36, Q-37, Q-38, Q-39, Q-40, phenyl, phenyl substituted with (Z2)p5a, or —C(O)R53;
R6 is C1-6 alkyl, C1-6 haloalkyl, phenyl, phenyl substituted with (Z2)p5a, U-6, U-7, U-8, Q-10, or —NR28R29;
R7 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy (C1-2) alkyl, C1-6 alkylthio (C1-2) alkyl, C3-6 cycloalkyl (C1-2) alkyl, benzyl, or benzyl substituted with (Z4)p5c;
R8 and R9 are each independently a hydrogen atom, or C1-6 alkyl;
R10 is a halogen atom, —OR40, —S(O)r3R41, —CN, C3-6 cycloalkyl, (C3-6 cycloalkyl substituted with R44, Q-6, Q-7, Q-10, Q-11, Q-12, or Q-13;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6 alkyl substituted with R12, C3-6 cycloalkyl, (C1-6 cycloalkyl substituted with R44, phenyl, phenyl substituted with (Z4)p5c, tri(C1-4 alkyl)silyl, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, —C(═W2)R13, —S(O)r5R49, U-1, U-2, U-3, U-4, U-5, U-12, U-14, U-15, U-16, Q-17, Q-18, Q-19, or Q-20;
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl, (C1-6 cycloalkyl substituted with R45, —OR48, —S(O)r5R49, —CN, phenyl, phenyl substituted with (Z3)p5b, —C(═W2)R13, U-1, U-2, U-3, U-4, U-5, U-9, U-10, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, U-34, U-35, Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, Q-36, or —ON═CR42R43;
Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, Q-36, Q-37, Q-38, Q-39, and Q-40 are respectively the following structures:
Y2 is substituted on the aromatic ring of each of Q-1 to Q-40;
U-1, U-2, U-3, U-4, U-5, U-6, U-7, U-8, U-9, U-10, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, U-34, and U-35 are respectively the following structures:
R13 is a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, di(C1-6) alkylamino, C1-6 haloalkylamino, C1-6 alkylthio, C1-6 haloalkylthio, or —NH2;
R14 is a halogen atom, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-6 haloalkenyl, C2-6 haloalkynyl, (C3-6) cycloalkyl substituted with R45, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkoxy, C1-6 haloalkylthio, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, phenyl, phenyl substituted with (Z4)p5c, —CN, U-1, U-2, U-3, U-9, U-10, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, U-34, U-35, Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, or Q-36;
R15 and R16 are each independently a hydrogen atom, C1-6 alkyl, —C(O)R17, or —S(O)2R18;
R17 is C1-6 alkyl, C1-6 alkoxy, or C1-6 alkoxy (C1-2) alkyl;
R18 is C1-6 alkyl or C1-6 haloalkyl;
R19 is C3-6 cycloalkyl or tri(C1-6 alkyl)silyl;
R20 is a hydrogen atom, C1-6 alkyl, or C1-6 alkoxy;
R21 is a hydrogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy (C1-2) alkyl, or C1-6 alkylthio (C1-2) alkyl;
R22 is a halogen atom, —OH, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylthio, —CN, or Q-7;
R23 is C1-6 alkyl, C1-6 alkoxy, di(C1-6) alkylamino, phenyl, phenyl substituted with (Z4)p5c, U-6, U-7, or U-8;
R24 is C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, C3-6 haloalkenyl, C3-6 alkynyl, C3-6 haloalkynyl, (C1-6) alkoxy (C1-2) alkyl, —C(O)R25, —S(O)2R33, phenyl, or phenyl substituted with (Z4)p5c;
R25 is C1-6 alkyl, C1-6 alkoxy, phenyl, phenyl substituted with (Z4)p5c, di(C1-6) alkylamino, U-6, U-7, or U-8;
R26 is a halogen atom, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, —CN, —OR32, phenyl, phenyl substituted with (Z4)p5c, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, Q-36, U-1, U-2, U-3, U-4, U-5, U-9, U-10, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, U-34, or U-35;
R27 is a halogen atom, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, C3-6 halocycloalkyl, C1-6 alkylthio, C1-6 haloalkylthio, —CN, phenyl, phenyl substituted with (Z3)p5b, 9-fluorenyl, Q-2, Q-3, Q-4, Q-5, Q-17, U-1, U-2, U-3, U-4, U-5, U-9, U-10, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, U-34, or U-35;
R28 and R29 are each independently a hydrogen atom or C1-6 alkyl;
R30 and R31 are each independently a hydrogen atom, C1-6 alkyl, or benzyl;
R32 is phenyl, phenyl substituted with (Z4)p5c, or Q-17;
R33 is C1-6 alkyl, C1-6 haloalkyl, or di(C1-6 alkyl)amino;
R34 is a halogen atom, C1-6 alkoxy, phenyl, or —CN;
R35 is a hydrogen atom, C1-6 alkyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R14, (C1-6) cycloalkyl substituted with R44, or —S(O)2R33;
R36 is C1-6 alkyl, (C1-6) alkyl substituted with R37, C3-6 cycloalkyl, or (C1-6) cycloalkyl substituted with R44;
R37 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl, C3-6 halocycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, phenyl, phenyl substituted with (Z4)p5c, —CN, U-1, U-2, U-3, U-9, U-10, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, U-34, U-35, Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, or C1-10 alkoxycarbonyl;
R38 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-6 cycloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, (C1-6) alkyl substituted with R39, (C3-6) cycloalkyl substituted with R44, U-1, U-2, U-4, U-5, U-6, U-7, U-8, U-12, U-14, U-15, U-16, or —NR60R61;
R39 is a halogen atom, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, —OR51, —S(O)R52, —C(═W2)R13, —CN, phenyl, phenyl substituted with (Z)p5b, U-1, U-2, U-3, U-4, U-5, U-9, U-10, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, U-34, U-35, Q-1, Q-2, Q-3, Q-4, Q-5, Q-8, Q-9, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, Q-36, or —ON═CR42R43;
R40 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R46, (C3-6) cycloalkyl substituted with R44, or U-4;
R41 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, or (C1-6) alkyl substituted with R47;
R42 and R43 are each independently a hydrogen atom, C1-6 alkyl, phenyl, or phenyl substituted with (Z4)p5c, or R42 and R43 form C3-6 cycloalkyl together with the carbon atom to which R42 and R43 are bonded;
R44 is a halogen atom, C1-6 alkyl, or —CN;
R45 is a halogen atom, C1-6 alkyl, or —CN;
R46 is C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, —CN, U-1, U-2, U-3, U-4, U-5, U-9, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, or Q-36;
R47 is C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, U-1, U-2, U-3, U-4, U-5, U-9, U-11, U-12, U-13, U-14, U-15, U-16, U-17, U-18, U-19, U-20, U-21, U-22, U-23, U-24, U-25, U-26, U-27, U-28, U-29, U-30, U-31, U-32, U-33, Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, Q-20, Q-21, Q-22, Q-23, Q-24, Q-25, Q-26, Q-27, Q-28, Q-29, Q-30, Q-31, Q-32, Q-33, Q-34, Q-35, Q-36, or —CN; R48 is a hydrogen atom, C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, C3-6 haloalkenyl, C3-6 alkynyl, C3-6 haloalkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, —C(O)R50, or —S(O)2R33;
R49 is C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, C3-6 haloalkenyl, C3-6 alkynyl, C3-6 haloalkynyl, C3-6 cycloalkyl, or (C3-6) cycloalkyl substituted with R44;
R50 is C1-6 alkyl, C1-6 alkoxy, or di(C1-6 alkyl)amino;
R51 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C3-6 haloalkenyl, or C3-6 haloalkynyl;
R52 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, or C3-6 cycloalkyl; R53 is C1-6 alkyl, C1-6 alkoxy, phenyl, or phenyl substituted with (Z4)p5c;
R54 is C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, C3-6 alkynyl, phenyl, or phenyl substituted with (Z4)p5c;
R55 is C1-6 alkyl, C1-6 alkoxy, —OH, or NR56R57;
R56 and R57 are each independently a hydrogen atom or C1-6 alkyl;
R58 is (C1-6) alkyl substituted with R27, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, phenyl, or phenyl substituted with (Z3)p5b;
R59 is C1-6 alkyl, C1-6 haloalkyl, C1-6 alkenyl, C1-6 alkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, phenyl, or phenyl substituted with (Z3)p5b;
R60 and R61 are each independently a hydrogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy (C1-6) alkyl, phenyl, phenyl substituted with (Z4)p5c, benzyl, or benzyl substituted with (Z4)p5c;
RN is a hydrogen atom or C1-6 alkyl;
Y2 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6haloalkylthio, —CN, —NH2, or —NO2, and when q4, q3, or q2 is an integer of 2 or more, each Y2 is the same as or different from each other;
Y3 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkoxycarbonyl, —CN, —C(O)OH, —OH, or —NH2, and when t is 2, each Y3 is the same as or different from each other;
Z2 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, —S(O)2NR56R57, —OH, —NH2, —CN, —NO2, or —C(O)R55, and when p5a is an integer of 2 or more, each Z2 is the same as or different from each other;
Z3 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, —CN, C1-6 alkoxycarbonyl, or —NO2, and when p5b is an integer of 2 or more, each Z3 is the same as or different from each other;
Z4 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, —CN, —NO2, or C1-6 alkoxycarbonyl, and when p5c is an integer of 2 or more, each Z4 is the same as or different from each other;
W2 is an oxygen atom or N—OR7;
W3 is an oxygen atom or N—OR21;
W4 is an oxygen atom or a sulfur atom;
r1 is an integer of 0, 1, or 2;
r2 is an integer of 0, 1, or 2;
r3 is an integer of 0, 1, or 2;
r4 is an integer of 0, 1, or 2;
r5 is an integer of 0, 1, or 2;
r6 is an integer of 0, 1, or 2;
n is an integer of 0, 1, 2, 3, or 4;
t is an integer of 0, 1, or 2;
p2 is an integer of 0, 1, or 2;
p3 is an integer of 0, 1, 2, or 3;
p4 is an integer of 0, 1, 2, 3, or 4;
p5 is an integer of 0, 1, 2, 3, 4, or 5;
p6 is an integer of 0, 1, 2, 3, 4, 5, or 6;
p7 is an integer of 0, 1, 2, 3, 4, 5, 6, or 7;
p5a is an integer of 1, 2, 3, 4, or 5;
p5b is an integer of 1, 2, 3, 4, or 5;
p5c is an integer of 1, 2, 3, 4, or 5;
q1 is an integer of 0 or 1;
q2 is an integer of 0, 1, or 2;
q3 is an integer of 0, 1, 2, or 3; and
q4 is an integer of 0, 1, 2, 3, or 4].
[2]
The pyridazinone compound and a salt thereof according to [1], wherein:
W1 is an oxygen atom;
Z1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, (C3-6) cycloalkyl substituted with R44, phenyl, phenyl substituted with (Z4)p5c, Q-3, —NR15R16, —OR35, —S(O)r1R36, —CN, —NO2, —C(O)OH, —C(═W3)R20, or —N═C(C6H5)2, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R1 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, or C1-6 alkyl substituted with R34;
R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, C1-6 alkoxy, or —NR30R31; R3 is D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-13, D-14, D-15, D-16, D-17, D-18, D-19, D-20, D-21, D-22, D-23, D-24, D-25, D-26, D-27, or D-28;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-6 haloalkenyl, C2-6 haloalkynyl, (C1-6) alkyl substituted with R10, C3-6 cycloalkyl substituted with R44, —OR11, —S(O)r2R38, —NR8R9, —CN, —NO2, —C(O)OH, —C(═W2)R13, phenyl, phenyl substituted with (Z4)p5c, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R4 is a halogen atom, —CN, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, —OR24, —S(O)r4R54, —C(O)R23, phenyl, or phenyl substituted with (Z4)p5c;
R5 is C1-6 alkyl, (C1-6) alkyl substituted with R26, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, —OR58, C3-6 cycloalkyl, C3-6 cycloalkyl substituted with R44, —NR56R57, U-1, U-6, U-7, U-8, Q-1, Q-2, Q-3, Q-4, Q-5, Q-7, Q-8, Q-9, Q-10, Q-17, Q-18, Q-19, Q-20, phenyl, phenyl substituted with (Z2)p5a, or —C(O)R53;
R6 is C1-6 alkyl, C1-6 haloalkyl, phenyl, phenyl substituted with (Z2)p5a, or —NR28R29;
R7 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy (C1-2) alkyl, or C1-6 alkylthio (C1-2) alkyl;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, phenyl, phenyl substituted with (Z4)p5c, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2, U-4, Q-17, Q-18, or Q-19;
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, —OR48, —S(O)r5R49, —CN, phenyl, phenyl substituted with (Z3)p5b, —C(═W2)R13, U-1, U-2, U-3, Q-1, Q-2, Q-3, Q-4, Q-5, Q-18, or —ON═CR42R43;
R14 is a halogen atom, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-6 haloalkenyl, C2-6 haloalkynyl, (C3-6) cycloalkyl substituted with R45, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, phenyl, phenyl substituted with (Z4)p5c, —CN, U-1, U-2, U-3, U-9, Q-17, Q-18, Q-19, or Q-20;
R19 is tri(C1-6 alkyl)silyl; R22 is a halogen atom, —OH, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, or —CN;
R23 is C1-6 alkyl, C1-6 alkoxy, di(C1-6) alkylamino, phenyl, phenyl substituted with (Z4)p5c, U-7, or U-8;
R24 is C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, C3-6 alkynyl, (C1-6) alkoxy (C1-2) alkyl, —C(O)R25, or —S(O)2R33;
R25 is C1-6 alkyl, C1-6 alkoxy, or di(C1-6) alkylamino;
R26 is a halogen atom, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, —OR32, phenyl, or phenyl substituted with (Z4)p5c;
R27 is a halogen atom, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, or C1-6 alkylthio;
R36 is C1-6 alkyl, (C1-6) alkyl substituted with R37, or C3-6 cycloalkyl;
R37 is a halogen atom, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkylthio, or C1-10 alkoxycarbonyl;
R38 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-6 cycloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, (C1-6) alkyl substituted with R39, or (C3-6) cycloalkyl substituted with R44;
R39 is a halogen atom, C3-6 cycloalkyl, —OR51, —S(O)r6R52, —C(═W2)R13, —CN, phenyl, phenyl substituted with (Z3)p5b, U-1, U-3, U-9, Q-1, or Q-18;
R40 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R46, or U-4;
R41 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, C3-6 cycloalkyl, or (C1-6) alkyl substituted with R47;
R46 is C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C3-6 cycloalkyl, —CN, U-1, U-3, or U-9;
R47 is C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, or —CN;
R48 is a hydrogen atom, C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, C3-6 haloalkenyl, C3-6 alkynyl, C3-6 haloalkynyl, or C3-6 cycloalkyl;
R49 is C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, or C3-6 alkynyl;
R51 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, or C1-6 haloalkyl;
R52 is C1-6 alkyl, C3-6 alkenyl, or C3-6 alkynyl;
R54 is C1-6 alkyl or C3-6 alkenyl;
R59 is C1-6 alkyl, C1-6 alkenyl, or phenyl;
Y2 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, or C1-6 haloalkylthio; and
Z2 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, —OH, —NH2, —CN, —NO2, or —C(O)R55, and when p5a is an integer of 2 or more, each Z2 is the same as or different from each other.
[3]
The pyridazinone compound and a salt thereof according to [2], wherein:
Z1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, phenyl, phenyl substituted with (Z4)p5c, Q-3, —N15R16, —OR35, —S(O)r1R36, —CN, —C(═W3)R20, or —N═C(C6H5)2, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R1 is a hydrogen atom, C1-6 alkyl, or C1-6 alkyl substituted with R34;
R3 is D-1, D-2, D-3, D-4, D-6, D-7, D-8, D-9, D-10, D-17, D-18, D-19, D-20, D-21, D-22, D-23, D-24, D-25, D-26, or D-28;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, C2-6 alkenyl, (C1-6) alkyl substituted with R10, —C(O)OH, —OR11, —S(O)r2R38, —NR8R9, —CN, —NO2, —C(═W2)R13, phenyl, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R4 is a halogen atom, —CN, C2-6 alkenyl, C2-6 alkynyl, —OR24, —S(O)r4R54, —C(O)R23, or phenyl;
R5 is C1-6 alkyl, (C1-6) alkyl substituted with R26, C2-6 alkenyl, C1-6 alkoxy, —OR58, —SR59, C3-6 cycloalkyl, —NR56R57, U-1, U-6, Q-2, Q-4, phenyl substituted with (Z2)p5a, or —C(O)R53;
R6 is C1-6 alkyl, phenyl substituted with (Z2)p5a, or —NR28R29;
R7 is a hydrogen atom or C1-6 alkyl;
R8 and R9 are each independently C1-6 alkyl;
R10 is a halogen atom, —OR40, or —S(O)r3R41;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, phenyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2, U-4, or Q-17;
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, —OR48, —CN, phenyl, —C(═W2)R13, U-3, Q-1, or —ON═CR42R43;
R13 is C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkylamino;
R14 is a halogen atom, C2-6 alkenyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, phenyl, or U-1;
R18 is C1-6 alkyl;
R21 is a hydrogen atom or C1-6 alkyl;
R22 is a halogen atom, —OH, or C1-6 alkoxy;
R23 is C1-6 alkyl, C1-6 alkoxy, or phenyl;
R24 is C1-6 alkyl, (C1-6) alkoxy (C1-2) alkyl, or —C(O)R25;
R25 is C1-6 alkoxy;
R26 is C1-6 alkoxy, —OR32, or phenyl;
R27 is a halogen atom, C2-6 alkenyl, or C1-6 alkoxy;
R28 and R29 are each independently C1-6 alkyl;
R30 and R31 are each independently a hydrogen atom or benzyl;
R32 is phenyl;
R33 is C1-6 haloalkyl or di(C1-6) alkylamino;
R34 is C1-6 alkoxy, phenyl, or —CN;
R35 is a hydrogen atom, C1-6 alkyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R14, or —S(O)2R33;
R36 is C1-6 alkyl or (C1-6) alkyl substituted with R37;
R37 is a halogen atom or (C1-10) alkoxycarbonyl;
R38 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-6 cycloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, or (C1-6) alkyl substituted with R39;
R39 is a halogen atom, —OR51, —S(O)r6R52, —C(═W2)R13, or —CN;
R40 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C1-6 haloalkyl, or (C1-6) alkyl substituted with R46;
R41 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, or (C1-6) alkyl substituted with R47;
R42 and R43 are each independently C1-6 alkyl;
R45 is a halogen atom;
R46 is C1-6 alkoxy or C1-6 alkylthio;
R47 is C1-6 alkoxy or C1-6 alkylthio;
R48 is C1-6 alkyl or C1-6 haloalkyl;
R49 is C1-6 alkyl;
R51 is C1-6 alkyl;
R52 is C1-6 alkyl;
R53 is phenyl;
R54 is C1-6 alkyl;
R56 and R57 are each independently C1-6 alkyl;
R58 is (C1-6) alkyl substituted with R27 or phenyl;
R59 is C1-6 alkyl or phenyl;
Y2 is a halogen atom or C1-6 haloalkyl;
Z2 is a halogen atom, C1-6 alkyl, or C1-6 alkoxy, and when p5a is an integer of 2 or more, each Z2 is the same as or different from each other;
Z4 is a halogen atom or C1-6 alkoxy, and when p5c is an integer of 2 or more, each Z4 is the same as or different from each other; and
t is 0.
[4]
The pyridazinone compound and a salt thereof according to [3], wherein:
Z1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, —NR15R16, —OR35, —S(O)r1R36, or —CN, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, or C1-6 alkoxy;
R3 is D-1, D-2, D-3, D-4, D-6, D-7, D-8, D-9, D-10, D-17, D-18, D-20, D-21, D-22, D-23, D-24, or D-28;
Y1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, (C1-6) alkyl substituted with R10, —OR11, —S(O)r2R38, —NR8R9, —CN, —NO2, or —C(═W2)R13, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, phenyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2, or U-4; and
R37 is a halogen atom.
[5]
The pyridazinone compound or a salt thereof according to [3] or [4], wherein X is a sulfur atom.
[6]
The pyridazinone compound or a salt thereof according to [2], wherein:
X is an oxygen atom;
Z1 is a halogen atom, C1-6 alkyl, —OR35, or —S(O)r1R36, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R1 is C1-6 alkyl;
R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, or C1-6 alkoxy;
R3 is D-1, D-3, D-7, D-20, D-21, D-22, or D-24;
Y1 is a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —OR11, or —S(O)r2R38, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R4 is —OR24 or —S(O)r4R54;
R5 is C1-6 alkyl, (C1-6) alkyl substituted with R26, or C1-6 alkoxy;
R6 is C1-6 alkyl or —NR28R29;
R10 is a halogen atom, —OR40, or —S(O)r3R41;
R11 is a hydrogen atom, C1-6 alkyl, or (C1-6) alkyl substituted with R12;
R12 is a halogen atom, C2-6 alkenyl, —OR48, —S(O)r5R49, phenyl, or —C(═W2)R13;
R13 is a hydrogen atom or C1-6 alkyl;
R14 is a halogen atom, C2-6 alkenyl, C1-6 alkoxy, or C1-6 alkylthio;
R24 is C1-6 alkyl;
R26 is C1-6 alkoxy;
R28 and R29 are each independently C1-6 alkyl;
R34 is C1-6 alkoxy or —CN;
R35 is C1-6 alkyl or (C1-6) alkyl substituted with R14;
R36 is C1-6 alkyl or (C1-6) alkyl substituted with R37;
R37 is a halogen atom, C1-6 alkoxy, or C1-6 alkylthio;
R38 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, or (C1-6) alkyl substituted with R39;
R39 is —OR51 or —S(O)r6R52;
R40 is C1-6 alkyl, C3-6 alkenyl, or C3-6 alkynyl;
R41 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, or (C1-6) alkyl substituted with R47;
R48 is C1-6 alkyl;
r1 is an integer of 0, 1, or 2;
r4 is an integer of 0, 1, or 2;
r5 is an integer of 0, 1, or 2;
r6 is an integer of 0, 1, or 2;
n is an integer of 0, 1, 2, 3, or 4;
p3 is an integer of 0, 1, 2, or 3;
p4 is an integer of 0, 1, 2, 3, or 4; and
p5 is an integer of 0, 1, 2, 3, 4, or 5.
[7]
The pyridazinone compound or a salt thereof according to [6], wherein: Z1 is a halogen atom, C1-6 alkyl, or —OR35;
R1 is C1-6 alkyl;
R2 is C1-6 alkyl or C1-6 alkoxy;
R3 is D-1, D-7, or D-24;
Y1 is a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —OR11, or —S(O)r2R38;
G is a hydrogen atom, C1-6 alkyl, or —C(═W4)R5;
R5 is C1-6 alkyl;
R10 is a halogen atom or —OR40;
R12 is a halogen atom, C2-6 alkenyl, —OR48, —S(O)r5R49, or phenyl;
R35 is C1-6 alkyl;
R38 is C1-6 alkyl;
R40 is C1-6 alkyl;
R48 is C1-6 alkyl; and
R49 is C1-6 alkyl.
[8]
The pyridazinone compound and a salt thereof according to [5], wherein:
Z1 is a halogen atom, C1-6 alkyl, —OR35, or —S(O)r1R36, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R1 is C1-6 alkyl;
R2 is a hydrogen atom, a halogen atom, or C1-6 alkyl;
R3 is D-1 or D-3;
R4 is —OR24;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —OR11, —S(O)r2R38, or —C(═W2)R13, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R7 is C1-6 alkyl;
R11 is C1-6 alkyl, (C1-6) alkyl substituted with R12, or C3-6 cycloalkyl;
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, —OR48, —CN, —C(═W2)R13, or —ON═CR42R43,
R14 is a halogen atom, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, C1-6 alkylthio, C1-6 alkylsulfonyl, or U-1;
R24 is C1-6 alkyl or (C1-6) alkoxy (C1-2) alkyl;
R35 is C1-6 alkyl or (C1-6) alkyl substituted with R14;
R38 is C1-6 alkyl, C3-6 cycloalkyl, or (C1-6) alkyl substituted with R39;
R39 is a halogen atom, —OR51, —S(O)r6R52, —C(═W2)R13, or —CN;
R40 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C1-6 haloalkyl, or (C1-6) alkyl substituted with R46;
R41 is a hydrogen atom, C1-6 alkyl, C1-6 haloalkyl, or (C1-6) alkyl substituted with R47;
R46 is C1-6 alkoxy or C1-6 alkylthio; and
W2 is N—OR7.
[9]
The pyridazinone compound and a salt thereof according to [8], wherein:
G is a hydrogen atom;
R11 is C1-6 alkyl or (C1-6) alkyl substituted with R12;
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, —OR48, —S(O)r5R49, or —C(═W2)R13;
R36 is C1-6 alkyl;
R38 is C1-6 alkyl or (C1-6) alkyl substituted with R39; and n is an integer of 0 or 1.
[10]
The pyridazinone compound and a salt thereof according to [3], wherein:
W1 is an oxygen atom;
Z1 is C1-6 alkyl, (C1-6) alkyl substituted with R22, phenyl substituted with (Z)p5c, —NR15R16, —OR35, —C(═W3)R20, or —N═C(C6H5)2, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
G is a hydrogen atom, C1-6 alkyl, or (C1-6) alkyl substituted with R4;
R1 is a hydrogen atom, C1-6 alkyl, or C1-6 alkyl substituted with R34;
R2 is a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, or —NR30R31;
R3 is D-1, D-3, D-4, or D-6;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —C(O)OH, —CN, —C(═W2)R13, phenyl, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R4 is a halogen atom, —CN, C2-6 alkenyl, C2-6 alkynyl, or phenyl;
R7 is a hydrogen atom or C1-6 alkyl;
R8 and R9 are each independently C1-6 alkyl;
R10 is a halogen atom, —OR40, or —S(O)r3R41;
R13 is C1-6 alkyl or C1-6 alkoxy;
R14 is a halogen atom, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, or C1-6 alkylsulfonyl;
R15 and R16 are each independently a hydrogen atom or C1-6 alkyl;
R20 is a hydrogen atom or C1-6 alkyl;
R21 is a hydrogen atom or C1-6 alkyl;
R22 is —OH or C1-6 alkoxy;
R27 is a halogen atom or C1-6 alkoxy;
R30 and R31 are a hydrogen atom;
R33 is C1-6 haloalkyl or di(C1-6) alkylamino;
R34 is C1-6 alkoxy or —CN;
R35 is a hydrogen atom, C1-6 alkyl, or (C1-6) alkyl substituted with R14;
R40 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, or C1-6 haloalkyl;
R41 is a hydrogen atom, C1-6 alkyl, or C1-6 haloalkyl;
Z4 is a halogen atom or C1-6 alkoxy, and when p5c is an integer of 2 or more, each Z4 is the same as or different from each other;
W2 is an oxygen atom or N—OR7; and
W3 is an oxygen atom or N—OR21.
[11]
The pyridazinone compound and a salt thereof according to [3], wherein:
n is 0.
[12]
The pyridazinone compound and a salt thereof according to [4], wherein:
G is a hydrogen atom;
R1 is C1-6 alkyl;
R2 is a halogen atom or C1-6 alkyl;
R3 is D-1;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —OR11, or —S(O)r2R38, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
Z1 is a halogen atom or —OR35, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R10 is a halogen atom;
R11 is C1-6 alkyl or (C1-6) alkyl substituted with R12;
R12 is a halogen atom, —OR48, or S(O)r5R49;
R35 is C1-6 alkyl or (C1-6) alkyl substituted with R14;
R38 is C1-6 alkyl or (C1-6) alkyl substituted with R39;
R39 is a halogen atom; and
n is 0 or 1.
[13]
The pyridazinone compound and a salt thereof according to [3], wherein:
Z1 is —OR35, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R1 is C1-6 alkyl;
R2 is a hydrogen atom, a halogen atom, or C1-6 alkyl;
R3 is D-1, D-3, or D-7;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —OR11, —S(O)r2R38, —CN, or —C(═W2)R13, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R7 is C1-6 alkyl; and
W2 is N—OR7.
[14]
The pyridazinone compound and a salt thereof according to [3], wherein:
X is a sulfur atom;
Z1 is a halogen atom, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R1 is C1-6 alkyl;
R2 is a hydrogen atom, a halogen atom, or C1-6 alkyl;
R3 is D-1;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —OR11, —S(O)r2R38, —CN, or —C(═W2)R13, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R7 is C1-6 alkyl;
R13 is C1-6 alkyl; and
W2 is N—OR7.
[15]
The pyridazinone compound and a salt thereof according to [3], wherein:
Z1 is C3-6 cycloalkyl, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R1 is C1-6 alkyl;
R2 is a hydrogen atom, a halogen atom, or C1-6 alkyl;
R3 is D-1 or D-3;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —OR11, —S(O)r2R38, —CN, or —C(═W2)R13, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
R7 is C1-6 alkyl; and
W2 is N—OR7.
[16]
The pyridazinone compound and a salt thereof according to [7], wherein:
R3 is D-1;
R10 is a halogen atom; and
n is an integer of 0 or 1.
[17]
The pyridazinone compound and a salt thereof according to [9], wherein:
Y1 is a hydrogen atom, a halogen atom, or —OR11, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
Z1 is a halogen atom, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R11 is (C1-6) alkyl substituted with R12;
R12 is a halogen atom; and
[18]
The pyridazinone compound and a salt thereof according to [9], wherein:
Y1 is a hydrogen atom, C1-6 alkyl, or (C1-6) alkyl substituted with R10, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other;
Z1 is C1-6 alkyl or —OR35, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R14 is a halogen atom or C1-6 alkoxy;
R35 is a hydrogen atom, C1-6 alkyl, or (C1-6) alkyl substituted with R14; and
n is 0 or 1.
[19]
The pyridazinone compound or a salt thereof according to any of [1] to [3], wherein:
Za is a hydrogen atom, a halogen atom, C1-6 alkyl, or —OR35;
Zb is a hydrogen atom, a halogen atom, C1-6 alkyl, or (C1-6) alkyl substituted with R22;
Zc is a hydrogen atom, a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, phenyl, phenyl substituted with (Z4)p5c, Q-3, —NR15R16, —OR35, —S(O)r1R36, —CN, —C(═W3)R20, or —N═C(C6H5)2;
Zd is a hydrogen atom or a halogen atom;
R14 is a halogen atom, C2-6 alkenyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, phenyl, or U-1;
R15 and R16 are each independently a hydrogen atom, C1-6 alkyl, —C(O)R17, or —S(O)2R18;
R17 is C1-6 alkyl, C1-6 alkoxy, or C1-6 alkoxy (C1-2) alkyl;
R18 is C1-6 alkyl;
R19 is tri(C1-6 alkyl)silyl;
R20 is a hydrogen atom or C1-6 alkyl;
R21 is a hydrogen atom or C1-6 alkyl;
R22 is a halogen atom, —OH, or C1-6 alkoxy;
R33 is di(C1-6) alkylamino;
R35 is a hydrogen atom, C1-6 alkyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R14, or —S(O)2R33;
R36 is C1-6 alkyl or (C1-6) alkyl substituted with R37;
R37 is a halogen atom or (C1-10) alkoxycarbonyl;
R45 is a halogen atom;
Z4 is a halogen atom or C1-6 alkoxy, and when p5c is an integer of 2 or more, each Z4 is the same as or different from each other;
W3 is an oxygen atom or N—OR21;
r1 is an integer of 0 or 2;
p5c is an integer of 1 or 2; and
q3 is 0.
[20]
The pyridazinone compound or a salt thereof according to any of [1] to [19], wherein:
W1 is an oxygen atom.
[21]
The pyridazinone compound or a salt thereof according to any of [1] to [19], wherein:
W1 is a sulfur atom.
[22]
The pyridazinone compound or a salt thereof according to any of [1] to [21], wherein:
Z1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, (C3-6) cycloalkyl substituted with R44, phenyl, phenyl substituted with (Z4)p5c, Q-3, —NR15R16, —OR35, —S(O)r1R36, —CN, —NO2, —C(O)OH, —C(═W3)R20, or —N═C(C6H5)2, and when n is an integer of 2 or more, each Z1 is the same as or different from each other.
[23]
The pyridazinone compound or a salt thereof according to [22], wherein:
Z1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, phenyl, phenyl substituted with (Z4)p5c, Q-3, —N15R16, —OR35, —S(O)r1R36, —CN, —C(═W3)R20, or —N═C(C6H5)2, and when n is an integer of 2 or more, each Z1 is the same as or different from each other.
[24]
The pyridazinone compound or a salt thereof according to [22], wherein:
Z1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, —NR15R16, —OR35, —S(O)r1R36, or —CN, and when n is an integer of 2 or more, each Z1 is the same as or different from each other.
[25]
The pyridazinone compound or a salt thereof according to [22], wherein:
Z1 is a halogen atom, C1-6 alkyl, —OR35, or —S(O)r1R36, and when n is an integer of 2 or more, each Z1 is the same as or different from each other.
[26]
The pyridazinone compound or a salt thereof according to [22], wherein:
Z1 is a halogen atom, C1-6 alkyl, or —OR35, and when n is an integer of 2 or more, each Z1 is the same as or different from each other.
[27]
The pyridazinone compound or a salt thereof according to any of [1] to [26], wherein:
G is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R4, —C(═W4)R5, or —S(O)2R6.
[28]
The pyridazinone compound or a salt thereof according to [27], wherein:
G is a hydrogen atom, C1-6 alkyl, or —C(═W4)R5.
[29]
The pyridazinone compound or a salt thereof according to [27], wherein:
G is a hydrogen atom or C1-6 alkyl.
[30]
The pyridazinone compound or a salt thereof according to any of [1] to [29], wherein:
R1 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, or C1-6 alkyl substituted with R34.
[31]
The pyridazinone compound or a salt thereof according to [30], wherein:
R1 is a hydrogen atom, C1-6 alkyl, or C1-6 alkyl substituted with R34.
[32]
The pyridazinone compound or a salt thereof according to [30], wherein:
R1 is C1-6 alkyl.
[33]
The pyridazinone compound or a salt thereof according to any of [1] to [32], wherein:
R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, C1-6 alkoxy, or —NR30R31.
[34]
The pyridazinone compound or a salt thereof according to [33], wherein:
R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, or C1-6 alkoxy.
[35]
The pyridazinone compound or a salt thereof according to [33], wherein:
R2 is C1-6 alkyl or C1-6 alkoxy.
[36]
The pyridazinone compound or a salt thereof according to [33], wherein:
R2 is C1-6 alkoxy, C3-6 cycloalkyl, or —NR30R31.
[37]
The pyridazinone compound or a salt thereof according to [33], wherein:
R2 is C3-6 cycloalkyl or —NR30R31.
[38]
The pyridazinone compound or a salt thereof according to any of [1] to [37], wherein:
R3 is D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-13, D-14, D-15, D-16, D-17, D-18, D-19, D-20, D-21, D-22, D-23, D-24, D-25, D-26, D-27, or D-28.
[39]
The pyridazinone compound or a salt thereof according to [38], wherein:
R3 is D-1, D-2, D-3, D-4, D-6, D-7, D-8, D-9, D-10, D-17, D-18, D-19, D-20, D-21, D-22, D-23, D-24, D-25, D-26, or D-28.
[40]
The pyridazinone compound or a salt thereof according to [38], wherein:
R3 is D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-17, D-18, D-20, D-21, D-22, D-23, D-24, or D-28.
[41]
The pyridazinone compound or a salt thereof according to [38], wherein:
R3 is D-1, D-3, D-7, D-20, D-21, D-22, or D-24.
[42]
The pyridazinone compound or a salt thereof according to [38], wherein:
R3 is D-1, D-7, or D-24.
[43]
The pyridazinone compound or a salt thereof according to [38], wherein:
R3 is D-1.
[44]
The pyridazinone compound or a salt thereof according to [38], wherein:
R3 is D-3.
[45]
The pyridazinone compound or a salt thereof according to [38], wherein:
R3 is D-7.
[46]
The pyridazinone compound or a salt thereof according to [38], wherein:
R3 is D-24.
[47]
The pyridazinone compound or a salt thereof according to any of [1] to [46], wherein:
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-6 haloalkenyl, C2-6 haloalkynyl, (C1-6) alkyl substituted with R10, C3-6 cycloalkyl substituted with R44, —OR11, —S(O)r2R38, —NR8R9, —CN, —NO2, —C(O)OH, —C(═W2)R13, phenyl, phenyl substituted with (Z4)p5c, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[48]
The pyridazinone compound or a salt thereof according to [47], wherein:
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, C2-6 alkenyl, (C1-6) alkyl substituted with R10, —C(O)OH, —OR11, —S(O)r2R38, —NR8R9, —CN, —NO2, —C(═W2)R13, phenyl, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[49]
The pyridazinone compound or a salt thereof according to [47], wherein:
Y1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, (C1-6) alkyl substituted with R10, —OR11, —S(O)r2R38, —NR8R9, —CN, —NO2, or —C(═W2)R13, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[50]
The pyridazinone compound or a salt thereof according to [47], wherein:
Y1 is a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —OR11, or —S(O)r2R38, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[51]
The pyridazinone compound or a salt thereof according to [47], wherein: Y1 is a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, or —OR11, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[52]
The pyridazinone compound or a salt thereof according to [47], wherein:
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R10, —C(O)OH, —CN, —C(═W2)R13, phenyl, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[53]
The pyridazinone compound or a salt thereof according to [47], wherein:
Y1 is a hydrogen atom, C1-6 alkyl, or (C1-6) alkyl substituted with R10, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[54]
The pyridazinone compound or a salt thereof according to [47], wherein:
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, phenyl, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[55]
The pyridazinone compound or a salt thereof according to [47], wherein:
Y1 is —OR11 or —S(O)r2R38, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[56]
The pyridazinone compound or a salt thereof according to [47], wherein:
Y1 is a hydrogen atom, a halogen atom, or —OR11, and when p7, p6, p5, p4, p3, or p2 is an integer of 2 or more, each Y1 is the same as or different from each other.
[57]
The pyridazinone compound or a salt thereof according to any of [1] to [56], wherein:
R4 is a halogen atom, —CN, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, —OR24, —S(O)r4R54, —C(O)R23, phenyl, or phenyl substituted with (Z4)p5c.
[58]
The pyridazinone compound or a salt thereof according to [57], wherein:
R4 is a halogen atom, —CN, C2-6 alkenyl, C2-6 alkynyl, —OR24, —S(O)r4R54, —C(O)R23, or phenyl.
[59]
The pyridazinone compound or a salt thereof according to [57], wherein:
R4 is —OR24 or —S(O)r4R54.
[60]
The pyridazinone compound or a salt thereof according to any of [1] to [59], wherein:
R5 is C1-6 alkyl, (C1-6) alkyl substituted with R26, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, —OR58, —SR59, C3-6 cycloalkyl, C3-6 cycloalkyl substituted with R44, —NR56R57, U-1, U-6, U-7, U-8, Q-1, Q-2, Q-3, Q-4, Q-5, Q-7, Q-8, Q-9, Q-10, Q-17, Q-18, Q-19, Q-20, phenyl, phenyl substituted with (Z2)p5a, or —C(O)R53.
[61]
The pyridazinone compound or a salt thereof according to [60], wherein:
R5 is C1-6 alkyl, (C1-6) alkyl substituted with R26, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, —OR58, —SR59, C3-6 cycloalkyl, —NR56R57, U-1, U-6, Q-2, Q-4, phenyl, phenyl substituted with (Z2)p5a, or —C(O)R53.
[62]
The pyridazinone compound or a salt thereof according to [60], wherein:
R5 is C1-6 alkyl, (C1-6) alkyl substituted with R26, or C1-6 alkoxy.
[63]
The pyridazinone compound or a salt thereof according to [60], wherein:
R5 is C1-6 alkyl.
[64]
The pyridazinone compound or a salt thereof according to any of [1] to [63], wherein:
R6 is C1-6 alkyl, C1-6 haloalkyl, phenyl, phenyl substituted with (Z2)p5a, or —NR28R29.
[65]
The pyridazinone compound or a salt thereof according to [64], wherein:
R6 is C1-6 alkyl, phenyl substituted with (Z2)p5a, or —NR28R29.
[66]
The pyridazinone compound or a salt thereof according to [64], wherein:
R6 is C1-6 alkyl or —NR28R29.
[67]
The pyridazinone compound or a salt thereof according to any of [1] to [66], wherein:
R7 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy (C1-2) alkyl, or C1-6 alkylthio (C1-2) alkyl.
[68]
The pyridazinone compound or a salt thereof according to [67], wherein:
R7 is a hydrogen atom or C1-6 alkyl.
[69]
The pyridazinone compound or a salt thereof according to any of [1] to [68], wherein:
Rm is a halogen atom, —OR40, —S(O)r3R41, C3-6 cycloalkyl, or (C3-6) cycloalkyl substituted with R44.
[70]
The pyridazinone compound or a salt thereof according to [69], wherein: R10 is a halogen atom, —OR40, or —S(O)r3R41.
[71]
The pyridazinone compound or a salt thereof according to [69], wherein: R10 is a halogen atom or —OR40.
[72]
The pyridazinone compound or a salt thereof according to any of [1] to [71], wherein:
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R44, phenyl, phenyl substituted with (Z4)p5c, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2, U-4, Q-17, Q-18, or Q-19.
[73]
The pyridazinone compound or a salt thereof according to [72], wherein:
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, phenyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2, U-4, or Q-17.
[74]
The pyridazinone compound or a salt thereof according to [72], wherein:
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, phenyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2, or U-4.
[75]
The pyridazinone compound or a salt thereof according to [72], wherein:
R11 is C1-6 alkyl or (C1-6) alkyl substituted with R12.
[76]
The pyridazinone compound or a salt thereof according to any of [1] to [75], wherein:
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, —OR48, —S(O)r5R49, —CN, phenyl, phenyl substituted with (Z3)p5b, —C(═W2)R13, U-1, U-2, U-3, Q-1, Q-2, Q-3, Q-4, Q-5, Q-18, or —ON═CR42R43.
[77]
The pyridazinone compound or a salt thereof according to [76], wherein:
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, —OR48, —S(O)r5R49, —CN, phenyl, —C(═W2)R13, U-3, Q-1, or —ON═CR42R43.
[78]
The pyridazinone compound or a salt thereof according to [76], wherein:
R12 is a halogen atom, C2-6 alkenyl, —OR48, —S(O)r5R49, or —C(═W2)R13.
[79]
The pyridazinone compound or a salt thereof according to [76], wherein:
R12 is a halogen atom, C2-6 alkenyl, —OR48, or —S(O)r5R49.
[80]
The pyridazinone compound or a salt thereof according to any of [1] to [79], wherein:
R13 is C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkylamino.
[81]
The pyridazinone compound or a salt thereof according to [80], wherein:
R13 is a hydrogen atom or C1-6 alkyl.
[82]
The pyridazinone compound or a salt thereof according to any of [1] to [81], wherein:
R14 is a halogen atom, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-6 haloalkenyl, C2-6 haloalkynyl, (C3-6) cycloalkyl substituted with R45, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, phenyl, phenyl substituted with (Z4)p5c, —CN, U-1, U-2, U-3, U-9, Q-17, Q-18, Q-19, or Q-20.
[83]
The pyridazinone compound or a salt thereof according to [82], wherein:
R14 is a halogen atom, C2-6 alkenyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, phenyl, or U-1.
[84]
The pyridazinone compound or a salt thereof according to [82], wherein:
R14 is a halogen atom, C2-6 alkenyl, C1-6 alkoxy, or C1-6 alkylthio.
[85]
The pyridazinone compound or a salt thereof according to any of [1] to [84], wherein:
R15 and R16 are each independently a hydrogen atom, C1-6 alkyl, —C(O)R17, or —S(O)2R18.
[86]
The pyridazinone compound or a salt thereof according to [85], wherein:
R15 and R16 are each independently a hydrogen atom or C1-6 alkyl.
[87]
The pyridazinone compound or a salt thereof according to any of [1] to [86], wherein:
R17 is C1-6 alkyl, C1-6 alkoxy, or C1-6 alkoxy (C1-2) alkyl.
[88]
The pyridazinone compound or a salt thereof according to any of [1] to [87], wherein:
R22 is a halogen atom, —OH, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, or —CN.
[89]
The pyridazinone compound or a salt thereof according to [88], wherein:
R22 is a halogen atom, —OH, or C1-6 alkoxy.
[90]
The pyridazinone compound or a salt thereof according to any of [1] to [89], wherein:
R23 is C1-6 alkyl, C1-6 alkoxy, di(C1-6) alkylamino, phenyl, phenyl substituted with (Z4)p5c, U-7, or U-8.
[91]
The pyridazinone compound or a salt thereof according to [90], wherein:
R23 is C1-6 alkyl, C1-6 alkoxy, or phenyl.
[92]
The pyridazinone compound or a salt thereof according to any of [1] to [91], wherein:
R24 is C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, C3-6 alkynyl, (C1-6) alkoxy (C1-2) alkyl, —C(O)R25, or —S(O)2R33.
[93]
The pyridazinone compound or a salt thereof according to [92], wherein:
R24 is C1-6 alkyl, (C1-6) alkoxy (C1-2) alkyl, or —C(O)R25.
[94]
The pyridazinone compound or a salt thereof according to [92], wherein: R24 is C1-6 alkyl.
[95]
The pyridazinone compound or a salt thereof according to any of [1] to [94], wherein:
R25 is C1-6 alkyl, C1-6 alkoxy, or di(C1-6) alkylamino.
[96]
The pyridazinone compound or a salt thereof according to any of [1] to [95], wherein:
R26 is a halogen atom, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, —OR32, phenyl, or phenyl substituted with (Z4)p5c.
[97]
The pyridazinone compound or a salt thereof according to [96], wherein:
R26 is C1-6 alkoxy, —OR32, or phenyl.
[98]
The pyridazinone compound or a salt thereof according to [96], wherein:
R26 is C1-6 alkoxy.
[99]
The pyridazinone compound or a salt thereof according to any of [1] to [98], wherein:
R27 is a halogen atom, C2-6 alkenyl, or C1-6 alkoxy.
[100]
The pyridazinone compound or a salt thereof according to any of [1] to [99], wherein:
R34 is C1-6 alkoxy, phenyl, or —CN.
[101]
The pyridazinone compound or a salt thereof according to [100], wherein:
R34 is C1-6 alkoxy or —CN.
[102]
The pyridazinone compound or a salt thereof according to any of [1] to [101], wherein:
R35 is a hydrogen atom, C1-6 alkyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R14, or —S(O)2R33.
[103]
The pyridazinone compound or a salt thereof according to [102], wherein:
R35 is C1-6 alkyl or (C1-6) alkyl substituted with R14.
[104]
The pyridazinone compound or a salt thereof according to [102], wherein:
R35 is C1-6 alkyl.
[105]
The pyridazinone compound or a salt thereof according to any of [1] to [104], wherein:
R36 is C1-6 alkyl, (C1-6) alkyl substituted with R37, or C3-6 cycloalkyl.
[106]
The pyridazinone compound or a salt thereof according to [105], wherein:
R36 is C1-6 alkyl or (C1-6) alkyl substituted with R37.
[107]
The pyridazinone compound or a salt thereof according to any of [1] to [106], wherein:
R37 is a halogen atom, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkylthio, or C1-10 alkoxycarbonyl.
[108]
The pyridazinone compound or a salt thereof according to [107], wherein:
R37 is a halogen atom or (C1-10) alkoxycarbonyl.
[109]
The pyridazinone compound or a salt thereof according to [107], wherein:
R37 is a halogen atom.
[110]
The pyridazinone compound or a salt thereof according to any of [1] to [109], wherein:
R38 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-6 cycloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, (C1-6) alkyl substituted with R39, or (C3-6) cycloalkyl substituted with R44.
[111]
The pyridazinone compound or a salt thereof according to [110], wherein:
R38 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, or (C1-6) alkyl substituted with R39.
[112]
The pyridazinone compound or a salt thereof according to [110], wherein:
R38 is C1-6 alkyl.
[113]
The pyridazinone compound or a salt thereof according to any of [1] to [112], wherein:
R39 is a halogen atom, C3-6 cycloalkyl, —OR51, —S(O)r6R52, —C(═W2)R13, —CN, phenyl, phenyl substituted with (Z3)p5b, U-1, U-3, U-9, Q-1, or Q-18.
[114]
The pyridazinone compound or a salt thereof according to [113], wherein:
R39 is a halogen atom, —OR51, —S(O)r6R52, —C(═W2)R13, or —CN.
[115]
The pyridazinone compound or a salt thereof according to [113], wherein:
R39 is —OR51 or —S(O)r6R52.
[116]
The pyridazinone compound or a salt thereof according to any of [1] to [115], wherein:
R40 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R46, or U-4.
[117]
The pyridazinone compound or a salt thereof according to [116], wherein:
R40 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C1-6 haloalkyl, or (C1-6) alkyl substituted with R46.
[118]
The pyridazinone compound or a salt thereof according to [116], wherein:
R40 is C1-6 alkyl, C3-6 alkenyl, or C3-6 alkynyl.
The pyridazinone compound or a salt thereof according to [116], wherein:
R40 is C1-6 alkyl.
[120]
The pyridazinone compound or a salt thereof according to any of [1] to [119], wherein:
R41 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, C3-6 cycloalkyl, or (C1-6) alkyl substituted with R47.
[121]
The pyridazinone compound or a salt thereof according to [120], wherein:
R41 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, or (C1-6) alkyl substituted with R47.
[122]
The pyridazinone compound or a salt thereof according to [120], wherein:
R41 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, or (C1-6) alkyl substituted with R47.
[123]
The pyridazinone compound or a salt thereof according to any of [1] to [122], wherein:
R48 is a hydrogen atom, C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, C3-6 haloalkenyl, C3-6 alkynyl, C3-6 haloalkynyl, or C3-6 cycloalkyl.
[124]
The pyridazinone compound or a salt thereof according to [123], wherein:
R48 is C1-6 alkyl or C1-6 haloalkyl.
[125]
The pyridazinone compound or a salt thereof according to [123], wherein:
R48 is C1-6 alkyl.
[126]
The pyridazinone compound or a salt thereof according to any of [1] to [125], wherein:
R49 is C1-6 alkyl, C1-6 haloalkyl, C3-6 alkenyl, or C3-6 alkynyl.
[127]
The pyridazinone compound or a salt thereof according to [126], wherein:
R49 is C1-6 alkyl.
[128]
The pyridazinone compound or a salt thereof according to any of [1] to [127], wherein: Y2 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, or C1-6 haloalkylthio.
[129]
The pyridazinone compound or a salt thereof according to [128], wherein: Y2 is a halogen atom or C1-6 haloalkyl.
[130]
The pyridazinone compound or a salt thereof according to any of [1] to [129], wherein:
Z2 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, —OH, —NH2, —CN, —NO2, or —C(O)R55, and when p5a is an integer of 2 or more, each Z2 is the same as or different from each other.
[131]
The pyridazinone compound or a salt thereof according to [130], wherein: Z2 is a halogen atom, C1-6 alkyl, or C1-6 alkoxy, and when p5a is an integer of 2 or more, each Z2 is the same as or different from each other.
[132]
The pyridazinone compound or a salt thereof according to any of [1] to [131], wherein:
Z4 is a halogen atom, C1-6 alkyl, or C1-6 alkoxy, and when p5c is an integer of 2 or more, each Z3 is the same as or different from each other.
[133]
The pyridazinone compound or a salt thereof according to [132], wherein: Z4 is a halogen atom or C1-6 alkoxy, and when p5c is an integer of 2 or more, each Z3 is the same as or different from each other.
[134]
The pyridazinone compound or a salt thereof according to any of [1] to [133], wherein:
r1 is an integer of 0 or 2;
r2 is an integer of 0, 1, or 2;
r3 is an integer of 0, 1, or 2;
r5 is an integer of 0, 1, or 2; and
r6 is 0.
[135]
The pyridazinone compound or a salt thereof according to any of [1] to [134], wherein:
n is an integer of 0, 1, or 2.
[136]
The pyridazinone compound or a salt thereof according to any of [1] to [135], wherein:
p2 is an integer of 0 or 1;
p3 is an integer of 0, 1, 2, or 3;
p4 is an integer of 0, 1, or 2;
p5 is an integer of 0, 1, 2, 3, or 4;
p6 is an integer of 0, 1, or 2; and
p7 is an integer of 0, 1, or 2.
[137]
The pyridazinone compound or a salt thereof according to [136], wherein:
p2 is an integer of 1;
p3 is an integer of 0, 1, or 2;
p4 is an integer of 1;
p5 is an integer of 0, 1, 2, or 3;
p6 is an integer of 0; and
p7 is an integer of 0.
[138] The number of substituents (corresponding to Examples+a)
The pyridazinone compound or a salt thereof according to any of [1] to [137], wherein:
p5a is an integer of 1;
p5b is an integer of 1 or 2; and
p5c is an integer of 1 or 2.
[139]
The pyridazinone compound or a salt thereof according to [138], wherein:
p5a is an integer of 1; and
p5c is an integer of 1 or 2.
[140]
The pyridazinone compound or a salt thereof according to any of [1] to [139], wherein:
q1 is an integer of 0 or 1;
q2 is an integer of 0 or 1;
q3 is an integer of 0 or 1; and
q4 is an integer of 0 or 2.
[141]
The pyridazinone compound or a salt thereof according to [140], wherein:
q2 is an integer of 1;
q3 is 0; and
q4 is an integer of 2.
[142]
A production intermediate of the pyridazinone compound or a salt thereof according to any of [1] to [141], the production intermediate being of the following formula A:
[wherein X is an oxygen atom or a sulfur atom;
Z1 is a halogen atom, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R22, (C2-6) alkynyl substituted with R19, phenyl, phenyl substituted with (Z4)p5c, Q-3, —NR15R16, —OR35, —S(O)r1R36, —CN, —C(═W3)R20, or —N═C(C6H5)2, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, C2-6 alkenyl, (C1-6) alkyl substituted with R10, —C(O)OH, —OR11, —S(O)r2R38, —NR8R9, —CN, —NO2, —C(═W2)R13, phenyl, or tri(C1-6 alkyl)silyl, and when p5 is an integer of 2 or more, each Y1 is the same as or different from each other;
R7 is a hydrogen atom or C1-6 alkyl;
R8 and R9 are each independently C1-6 alkyl;
R10 is a halogen atom, —OR40, or —S(O)r3R41;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, phenyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2, U-4, or Q-17;
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with R45, —OR48, —S(O)r5R49, —CN, phenyl, —C(═W2)R13, U-3, Q-1, or —ON═CR42R43;
R13 is C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkylamino;
R14 is a halogen atom, C2-6 alkenyl, C3-6 cycloalkyl, (C3-6) cycloalkyl substituted with
R45, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, phenyl, or U-1;
R15 and R16 are each independently a hydrogen atom, C1-6 alkyl, —C(O)R17, or —S(O)2R18;
R17 is C1-6 alkyl, C1-6 alkoxy, or C1-6 alkoxy (C1-2) alkyl;
R18 is C1-6 alkyl;
R19 is tri(C1-6 alkyl)silyl;
R20 is a hydrogen atom or C1-6 alkyl;
R21 is a hydrogen atom or C1-6 alkyl;
R22 is a halogen atom, —OH, or C1-6 alkoxy;
R33 is C1-6 haloalkyl or di(C1-6) alkylamino;
R35 is a hydrogen atom, C1-6 alkyl, C3-6 cycloalkyl, (C1-6) alkyl substituted with R14, or —S(O)2R33;
R36 is C1-6 alkyl or (C1-6) alkyl substituted with R37;
R37 is a halogen atom or (C1-10) alkoxycarbonyl;
R38 is C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-6 cycloalkyl, C3-6 haloalkenyl, C3-6 haloalkynyl, or (C1-6) alkyl substituted with R39;
R39 is a halogen atom, —OR51, —S(O)r6R52, —C(═W2)R13, or —CN;
R40 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C1-6 haloalkyl, or (C1-6) alkyl substituted with R46;
R41 is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, or (C1-6) alkyl substituted with R47;
R42 and R43 are each independently C1-6 alkyl;
R44 is a halogen atom, C1-6 alkyl, or —CN;
R45 is a halogen atom;
R46 is C1-6 alkoxy or C1-6 alkylthio;
R47 is C1-6 alkoxy or C1-6 alkylthio;
R48 is C1-6 alkyl or C1-6 haloalkyl;
R49 is C1-6 alkyl;
R51 is C1-6 alkyl;
R52 is C1-6 alkyl;
Ra is —OH, C1-6 alkoxy, or —NRa1Ra2;
Ra1 is a hydrogen atom or C1-6 alkyl;
Ra2 is a hydrogen atom, —NH2, or —N═C(Ra3)Ra4;
Ra3 is a hydrogen atom or C1-6 alkyl;
Ra4 is C1-6 alkyl or C1-6 alkoxycarbonyl;
Y2 is a halogen atom or C1-6 haloalkyl;
W2 is an oxygen atom or N—OR7;
W3 is an oxygen atom or N—OR21;
Z4 is a halogen atom or C1-6 alkoxy, and when p5c is an integer of 2 or more, each Z4 is the same as or different from each other;
n is an integer of 0, 1, or 2;
p5 is an integer of 0, 1, 2, 3, 4, or 5;
q3 is 0; and
p5c is an integer of 1 or 2].
[143]
The production intermediate of the pyridazinone compound or a salt thereof according to [142], wherein:
Z1 is a halogen atom, C1-6 alkyl, or —OR35, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
Y1 is a hydrogen atom, a halogen atom, or —OR11, and when p5 is an integer of 2 or more, each Y1 is the same as or different from each other;
R11 is C1-6 alkyl or (C1-6) alkyl substituted with R12;
R12 is a halogen atom;
R14 is phenyl;
R35 is C1-6 alkyl or (C1-6) alkyl substituted with R14;
Ra is —OH, C1-6 alkoxy, or —NRa1Ra2;
Ra1 is C1-6 alkyl;
Ra2 is —NH2 or —N═C(Ra3)Ra4;
Ra3 is C1-6 alkyl;
Ra4 is C1-6 alkoxycarbonyl;
p5 is an integer of 0, 1, or 2; and
n is an integer of 0, 1, or 2.
[144]
The production intermediate of the pyridazinone compound or a salt thereof according to [143], wherein:
X is a sulfur atom; and
Ra is —OH or C1-6 alkoxy.
[145]
The production intermediate of the pyridazinone compound or a salt thereof according to [143], wherein:
X is a sulfur atom;
R35 is C1-6 alkyl; and
Ra is —NRa1Ra2.
[146]
The production intermediate of the pyridazinone compound or a salt thereof according to [143], wherein:
X is an oxygen atom;
Z1 is —OR35;
Y1 is —OR11;
R11 is C1-6 alkyl;
R35 is C1-6 alkyl;
Ra is —OH;
p5 is an integer of 1; and
n is an integer of 1.
[147]
A pyridazinone compound of the following Formula (1) or a salt thereof:
[wherein W1 is an oxygen atom or a sulfur atom;
X is an oxygen atom or a sulfur atom;
Z1 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, —OH, —NH2, —CN, —NO2, or —CO2H, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
G is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R4, —C(O)R5, or —S(O)2R6;
R1 is C1-6 alkyl, C3-6 alkenyl, or C3-6 alkynyl;
R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, or C1-6 alkoxy;
R3 is D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-17, D-20a, D-22a, D-24a, D-25, D-23, D-21a, or D-19a;
D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-17, D-20a, D-22a, D-24a, D-25, D-23, D-21a, and D-19a are respectively the following structures:
Y1 is substituted on the aromatic ring of each of D-1 to D-25;
Y1 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, —NR8R9, —CN, —NO2, —CO2H, —C(═W2)R13, phenyl, (C1-6) alkyl substituted with R10, or —OR11, and when p7, p5, p4, or p3 is an integer of 2 or more, each Y1 is the same as or different from each other;
W2 is an oxygen atom or N—OR7;
R4 is phenyl;
R5 is C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, phenyl, or phenyl substituted with (Z2)p5a;
R6 is C1-6 alkyl, C1-6 haloalkyl, phenyl, or phenyl substituted with (Z2)p5a;
R7 is a hydrogen atom or C1-6 alkyl;
R8 and R9 are each independently a hydrogen atom or C1-6 alkyl;
R10 is C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, or —CN;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, phenyl, tri(C1-4 alkyl)silyl, C1-6 alkylcarbonyl, or C1-6 alkylsulfonyl;
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, C3-6 halocycloalkyl, C1-6 alkylthio, C1-6 alkylsulfinyl, alkylsulfonyl, —CN, phenyl, phenyl substituted with (Z3)p5b, —C(═W2)R13, U-1a, U-2a, U-3a, or U-4a;
U-1a, U-2a, U-3a, and U-4a are respectively the following structures:
R13 is a hydrogen atom or C1-6 alkyl;
Z2 is a halogen atom, C1-6 alkyl, or C1-6 alkoxy, and when p5a is an integer of 2 or more, each Z2 is the same as or different from each other;
Z3 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, —CN, or —NO2, and when p5b is an integer of 2 or more, each Z3 is the same as or different from each other;
n is an integer of 0, 1, 2, 3, or 4;
p3 is an integer of 0, 1, 2, or 3;
p4 is an integer of 0, 1, 2, 3, or 4;
p5 is an integer of 0, 1, 2, 3, 4, or 5;
p7 is an integer of 0, 1, 2, 3, 4, 5, 6, or 7;
p5a is an integer of 1, 2, 3, 4, or 5; and
p5b is an integer of 1, 2, 3, 4, or 5].
[148]
The pyridazinone compound or a salt thereof according to [147], wherein:
W1 is an oxygen atom;
Z1 is a halogen atom, C1-6 alkyl, or C1-6 alkoxy, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
G is a hydrogen atom, C1-6 alkyl, —C(O)R5, or —S(O)2R6;
R1 is C1-6 alkyl;
R2 is a hydrogen atom, C1-6 alkyl, or C1-6 alkoxy;
R3 is D-1, D-3, D-6, D-8, D-9, D-10, D-17, D-20a, D-22a, D-24a, D-25, D-23, D-21a, or D-19a;
Y1 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, —NR8R9, —CN, —NO2, —C(═W2)R13, phenyl, or —OR11, and when p7, p5, p4, or p3 is an integer of 2 or more, each Y1 is the same as or different from each other;
R5 is C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, or phenyl substituted with (Z2)p5a;
R6 is C1-6 alkyl;
R8 and R9 are each independently C1-6 alkyl;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, or phenyl;
R12 is a halogen atom;
R13 is C1-6 alkyl;
Z2 is C1-6 alkyl;
n is an integer of 0, 1, or 2;
p3 is an integer of 0 or 1;
p4 is an integer of 0, 1, or 2;
p5 is an integer of 0, 1, 2, or 3;
p7 is an integer of 0; and
p5a is an integer of 1.
[149]
A pyridazinone compound of the following Formula (1) or a salt thereof:
[wherein W1 is an oxygen atom or a sulfur atom;
X is an oxygen atom or a sulfur atom;
Z1 is a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R22, C2-6 alkenyl, C2-6 alkynyl, (C2-6) alkynyl substituted with R19, C3-6 cycloalkyl, C1-6 alkoxy, (C1-6) alkoxy substituted with R14, phenyl, phenyl substituted with (Z4)p5c, Q-3a, —OH, —NR15R16, —OR35, —CN, —NO2, —CO2H, or —C(═W3)R20, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
G is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R4, —C(O)R5, or —S(O)2R6;
R1 is C1-6 alkyl, C3-6 alkenyl, or C3-6 alkynyl;
R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, C1-6 alkoxy, or —NR30R31;
R3 is D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-17, D-20a, D-22a, D-24a, D-25, D-23, D-21a, D-19a, D-26, or D-18;
D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-17, D-20a, D-22a, D-24a, D-25, D-23, D-21a, D-19a, D-26, and D-18 are respectively the following structures:
Y1 is substituted on the aromatic ring of each of D-1 to D-26;
Y1 is a hydrogen atom, a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, —NR8R9, —CN, —NO2, —CO2H, —C(═W2)R13, phenyl, (C1-6) alkyl substituted with R10, or —OR11, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, or p3 is an integer of 2 or more, each Y1 is the same as or different from each other;
R4 is a halogen atom, —CN, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkylthio, —C(O)R23, —OR24, or phenyl;
R5 is C1-6 alkyl, C1-6 alkyl substituted with R26, C1-6 alkoxy, (C1-6) alkoxy substituted with R27, C1-6 alkylthio, U-6a, Q-2a, phenyl, or phenyl substituted with (Z2)p5a;
R6 is C1-6 alkyl, C1-6 haloalkyl, phenyl, phenyl substituted with (Z2)p5a, or —NR28R29;
W2 is an oxygen atom or N—OR7;
R7 is a hydrogen atom or C1-6 alkyl;
R8 and R9 are each independently a hydrogen atom, or C1-6 alkyl;
R10 is C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, or —CN;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, phenyl, tri(C1-4 alkyl)silyl, C1-6 alkylcarbonyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2a, or U-4a;
R12 is a halogen atom, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, C3-6 halocycloalkyl, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, —CN, phenyl, phenyl substituted with (Z3)p5b, —C(═W2)R13, U-1a, U-2a, U-3a, U-4a, U-5a, or Q-1a;
U-1a, U-2a, U-3a, U-4a, U-5a, U-6a, Q-1a, Q-2a, and Q-3a are respectively the following structures:
R13 is a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkylamino;
R14 is a halogen atom, C3-6 cycloalkyl, C3-6 halocycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, phenyl, or U-1a;
R15 and R16 are each independently a hydrogen atom, C1-6 alkyl, —C(O)R17, or —S(O)2R18;
R17 is C1-6 alkyl, C1-6 alkoxy, or C1-6 alkoxy (C1-2) alkyl;
R18 is C1-6 alkyl or C1-6 haloalkyl;
R19 is tri(C1-6 alkyl)silyl;
R20 is a hydrogen atom or C1-6 alkyl;
W3 is an oxygen atom or N—OR21;
R21 is a hydrogen atom or C1-6 alkyl;
R22 is a halogen atom, —OH, or C1-6 alkoxy;
R23 is phenyl;
R24 is (C1-6) alkoxy (C1-2) alkyl or —C(O)R25;
R25 is C1-6 alkyl or C1-6 alkoxy;
R26 is a halogen atom, (C1-6) alkoxy, or —OR32;
R27 is (C1-6) alkoxy;
R28 and R29 are each independently a hydrogen atom or C1-6 alkyl;
R30 and R31 are each independently a hydrogen atom or benzyl;
R32 is phenyl;
R33 is C1-6 alkyl, C1-6 haloalkyl, or di(C1-6) alkylamino;
R35 is —SO2R33;
Z2 is a halogen atom, C1-6 alkyl, or C1-6 alkoxy, and when p5a is an integer of 2 or more, each Z2 is the same as or different from each other;
Z3 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, —CN, or —NO2, and when p5b is an integer of 2 or more, each Z3 is the same as or different from each other;
Z4 is a halogen atom, C1-6 alkyl, or C1-6 alkoxy, and when p5c is an integer of 2 or more, each Z3 is the same as or different from each other;
n is an integer of 0, 1, 2, 3, or 4;
p3 is an integer of 0, 1, 2, or 3;
p4 is an integer of 0, 1, 2, 3, or 4;
p5 is an integer of 0, 1, 2, 3, 4, or 5;
p6 is an integer of 0, 1, 2, 3, 4, 5, or 6;
p7 is an integer of 0, 1, 2, 3, 4, 5, 6, or 7;
p5a is an integer of 1, 2, 3, 4, or 5;
p5b is an integer of 1, 2, 3, 4, or 5; and
p5c is an integer of 1, 2, 3, 4, or 5].
[150]
The pyridazinone compound or a salt thereof according to [149], wherein:
W1 is an oxygen atom;
Z1 is a halogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R22, C2-6 alkenyl, C2-6 alkynyl, (C2-6) alkynyl substituted with R19, C3-6 cycloalkyl, C1-6 alkoxy, (C1-6) alkoxy substituted with R14, phenyl, phenyl substituted with (Z4)p5c, Q-3a, —OH, —NR15R16, —OR35, —CN, or —C(═W3)R20, and when n is an integer of 2 or more, each Z1 is the same as or different from each other;
R1 is C1-6 alkyl;
R3 is D-1, D-3, D-6, D-8, D-9, D-10, D-17, D-20a, D-22a, D-24a, D-25, D-23, D-21a, D-19a, D-26, or D-18;
Y1 is a halogen atom, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C1-6 alkylthio, C1-6 alkylsulfonyl, —NR8R9, —CN, —NO2, —CO2H, —C(═W2)R13, phenyl, (C1-6) alkyl substituted with R10, —OR11, or tri(C1-6 alkyl)silyl, and when p7, p6, p5, p4, or p3 is an integer of 2 or more, each Y1 is the same as or different from each other;
R4 is C2-6 alkynyl, C1-6 alkoxy, —C(O)R23, —OR24, or phenyl;
R5 is C1-6 alkyl, (C1-6) alkyl substituted with R26, C1-6 alkoxy, (C1-6) alkoxy substituted with R27, C1-6 alkylthio, U-6a, Q-2a, or phenyl substituted with (Z2)p5a;
R6 is C1-6 alkyl, phenyl substituted with (Z2)p5a, or —NR28R29;
R8 and R9 are each independently C1-6 alkyl;
R10 is C1-6 alkoxy;
R11 is a hydrogen atom, C1-6 alkyl, (C1-6) alkyl substituted with R12, C3-6 cycloalkyl, phenyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, U-2a, or U-4a;
R12 is a halogen atom, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-6 cycloalkyl, C3-6 halocycloalkyl, C1-6 alkylthio, —CN, phenyl, —C(═W2)R13, or Q-1a;
R13 is C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkylamino;
R14 is a halogen atom, C3-6 cycloalkyl, C3-6 halocycloalkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, phenyl, or U-1a;
R18 is C1-6 alkyl;
R20 is C1-6 alkyl;
R25 is C1-6 alkoxy;
R26 is C1-6 alkoxy, or —OR32;
R28 and R29 are C1-6 alkyl;
R33 is di(C1-6) alkylamino;
R35 is —SO2R33;
Z2 is a halogen atom or C1-6 alkyl;
Z4 is a halogen atom or C1-6 alkoxy;
n is an integer of 0, 1, or 2;
p3 is an integer of 0 or 1;
p4 is an integer of 0, 1, or 2;
p5 is an integer of 0, 1, 2, or 3;
p6 is an integer of 0;
p7 is an integer of 0; and
p5a is an integer of 1.
[151]
An agricultural chemical comprising, as an active ingredient, one or more selected from the pyridazinone compound and a salt thereof according to any of [1] to [141].
[152]
A herbicide comprising, as an active ingredient, one or more selected from the pyridazinone compound and a salt thereof according to any of [1] to [141].
The compound of the present invention exhibits excellent herbicidal activity against various weeds, and has high safety to target crops. Furthermore, the compound has almost no adverse effect on non-target living organisms, such as mammals, fishes, and beneficial insects, and has low environmental burden because of its low residual property.
Thus, the present invention can provide a herbicide useful in the agricultural and horticultural fields, such as paddy fields, farmlands, and orchards.
The compound of the present invention may include geometrical isomers (i.e., E-form and Z-form) depending on the types of substituents. The present invention includes an E-form, a Z-form, and a mixture containing an E-form and a Z-form in any proportions.
The compound of the present invention may include, depending on the types of substituents, optically active substances attributed to the presence of one or more asymmetric carbon atoms. The present invention includes all optically active substances or racemates.
The compound of the present invention may include tautomers depending on the types of substituents. The present invention includes all tautomers or a mixture containing tautomers in any proportions. For example, among compounds of Formula (1) (hereinafter will be referred to “compounds (1)”), the compound of the following Formula (1-1a), in which G is a hydrogen atom and W1 is an oxygen atom, may include a tautomer such as a compound of the following Formula (1-1a-1) or a compound of the following Formula (1-1a-2). Thus, in the case of introduction of the substituent G1 (G1 corresponds to structures represented by G (except for a hydrogen atom)) the enol structure (1-1a) is formed into a structure (1-1a-3), and the enol structure (1-1a-2) is formed into a structure (1-1a-4). The present invention includes all these structures.
The compound of the present invention may include one or more rotational isomers attributed to limited bond rotation caused by the steric hindrance between substituents. The present invention includes all rotational isomers or a mixture containing diastereomers in any proportions.
The compound of the present invention may be formed into an acid addition salt by any common method. Examples of the acid addition salt include salts of hydrohalic acids such as hydrogen fluoride, hydrogen chloride, hydrogen bromide, and hydrogen iodide; salts of inorganic acids such as nitric acid, sulfuric acid, phosphoric acid, chloric acid, and perchloric acid; salts of sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; salts of carboxylic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid, and citric acid; or salts of amino acids such as glutamic acid and aspartic acid.
Alternatively, the compound of the present invention may be formed into a metal salt by any common method. Examples of the metal salt include salts of alkali metals such as lithium, sodium, and potassium; salts of alkaline earth metals such as calcium, barium, and magnesium; salt of aluminum; or quaternary ammonium salts such as tetramethylammonium salt, tetrabutylammonium salt, and benzyltrimethylammonium salt.
The terms or phrases as used herein have the meanings or usages described below.
The term “agricultural chemical” as used herein refers to a insecticide, a miticides, a nematicide, a herbicide, and a fungicide in the agricultural and horticultural fields.
Examples of the “halogen atom” as used herein include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. The term “halo” as used herein also refers to such a halogen atom.
In the specific description of substituents in the present specification, the term “n-” refers to “normal”; the term “i-” refers to “iso”; the term “sec-” refers to “secondary”; and the term “tert-” refers to “tertiary.”
The expression “Ca-b alkyl” as used herein refers to a linear or branched hydrocarbon group having a carbon atom number of a to b. Specific examples of the Ca-b alkyl include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, n-pentyl, 1-ethylpropyl, 2,2-dimethylpropyl, and n-hexyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b haloalkyl” as used herein refers to a linear or branched hydrocarbon group having a carbon atom number of a to b wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. When the hydrocarbon group is substituted with two or more halogen atoms, these halogen atoms may be identical to or different from one another. Specific examples of the Ca-b haloalkyl include fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, dichloromethyl, trifluoromethyl, chlorodifluoromethyl, trichloromethyl, bromodifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2,2-trichloroethyl, 2-bromo-2,2-difluoroethyl, 1,1,2,2-tetrafluoroethyl, 2-chloro-1,1,2-trifluoroethyl, pentafluoroethyl, 2,2-difluoropropyl, 3,3,3-trifluoropropyl, 3-bromo-3,3-difluoropropyl, 2,2,3,3-tetrafluoropropyl, 2,2,3,3,3-pentafluoropropyl, 1,1,2,3,3,3-hexafluoropropyl, heptafluoropropyl, 2,2,2-trifluoro-1-methylethyl, 2,2,2-trifluoro-1-(trifluoromethyl)ethyl, 1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl, 2,2,2-trifluoro-1,1-dimethylethyl, 2,2,3,4,4,4-hexafluorobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, and nonafluorobutyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkenyl” as used herein refers to a linear or branched unsaturated hydrocarbon group having a carbon atom number of a to b and having one or more double bonds in the molecule. Specific examples of the Ca-b alkenyl include vinyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, and 3-methyl-3-butenyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b haloalkenyl” as used herein refers to a linear or branched unsaturated hydrocarbon group having a carbon atom number of a to b and having one or more double bonds in the molecule wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. When the hydrocarbon group is substituted with two or more halogen atoms, these halogen atoms may be identical to or different from one another. Specific examples of the Cab haloalkenyl include 2,2-difluorovinyl, 2,2-dichlorovinyl, 2-fluoro-2-propenyl, 2-chloro-2-propenyl, 3-chloro-2-propenyl, 2-bromo-2-propenyl, 3,3-difluoro-2-propenyl, 2,3-dichloro-2-propenyl, 3,3-dichloro-2-propenyl, 2,3,3-trifluoro-2-propenyl, 2,3,3-trichloro-2-propenyl, 1-(trifluoromethyl)ethenyl, 4,4-difluoro-3-butenyl, 3,4,4-trifluoro-3-butenyl, and 3-chloro-4,4,4-trifluoro-2-butenyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkynyl” as used herein refers to a linear or branched unsaturated hydrocarbon group having a carbon atom number of a to b and having one or more triple bonds in the molecule. Specific examples of the Cab alkynyl include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 1-hexynyl, 3-hexynyl, 3-methyl-1-pentynyl, 4-methyl-1-pentynyl, and 3,3-dimethyl-1-butynyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b haloalkynyl” as used herein refers to a linear or branched unsaturated hydrocarbon group having a carbon atom number of a to b and having one or more triple bonds in the molecule wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. When the hydrocarbon group is substituted with two or more halogen atoms, these halogen atoms may be identical to or different from one another. Specific examples of the Cab haloalkynyl include 2-chloroethynyl, 2-bromoethynyl, 2-iodoethynyl, 3-chloro-2-propynyl, 3-bromo-2-propynyl, and 3-iodo-2-propynyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkoxy” as used herein refers to an alkyl-O— group wherein the alkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b alkoxy include methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, i-butyloxy, sec-butyloxy, tert-butyloxy, n-pentyloxy, and n-hexyloxy. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b haloalkoxy” as used herein refers to a haloalkyl-O-group wherein the haloalkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b haloalkoxy include difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy, bromodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-chloro-1,1,2-trifluoroethoxy, and 1,1,2,3,3,3-hexafluoropropyloxy. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkylthio” as used herein refers to an alkyl-S— group wherein the alkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b alkylthio include methylthio, ethylthio, n-propylthio, i-propylthio, n-butylthio, i-butylthio, sec-butylthio, and tert-butylthio. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Cab haloalkylthio” as used herein refers to a haloalkyl-S-group wherein the haloalkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b haloalkylthio include difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, trichloromethylthio, bromodifluoromethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthio, 2-chloro-1,1,2-trifluoroethylthio, pentafluoroethylthio, 1,1,2,3,3,3-hexafluoropropylthio, heptafluoropropylthio, 1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethylthio, and nonafluorobutylthio. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Cab alkylsulfinyl” as used herein refers to an alkyl-S(O)-group wherein the alkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Cab alkylsulfinyl include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, i-propylsulfinyl, n-butylsulfinyl, i-butylsulfinyl, sec-butylsulfinyl, and tert-butylsulfinyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b haloalkylsulfinyl” as used herein refers to a haloalkyl-S(O)— group wherein the haloalkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b haloalkylsulfinyl include difluoromethylsulfinyl, trifluoromethylsulfinyl, chlorodifluoromethylsulfinyl, bromodifluoromethylsulfinyl, 2,2,2-trifluoroethylsulfinyl, 1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethylsulfinyl, and nonafluorobutylsulfinyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkylsulfonyl” as used herein refers to an alkyl-S(O)2— group wherein the alkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b alkylsulfonyl include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, i-propylsulfonyl, n-butylsulfonyl, i-butyl sulfonyl, sec-butyl sulfonyl, and tert-butyl sulfonyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b haloalkylsulfonyl” as used herein refers to a haloalkyl-S(O)2— group wherein the haloalkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b haloalkylsulfonyl include difluoromethylsulfonyl, trifluoromethylsulfonyl, chlorodifluoromethylsulfonyl, bromodifluoromethylsulfonyl, 2,2,2-trifluoroethylsulfonyl, 1,1,2,2-tetrafluoroethylsulfonyl, and 2-chloro-1,1,2-trifluoroethylsulfonyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b cycloalkyl” as used herein refers to a cyclic hydrocarbon group having a carbon atom number of a to b, and the hydrocarbon group can form a monocyclic or multi-cyclic structure of a 3-membered to 10-membered ring. Each ring is optionally substituted with alkyl within a range of the specified number of carbon atoms. Specific examples of the Ca-b cycloalkyl include cyclopropyl, 1-methylcyclopropyl, 2-methylcyclopropyl, 2,2-dimethylcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b halocycloalkyl” as used herein refers to a cyclic hydrocarbon group having a carbon atom number of a to b wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom, and the hydrocarbon group can form a monocyclic or multi-cyclic structure of a 3-membered to 10-membered ring. Each ring is optionally substituted with alkyl within a range of the specified number of carbon atoms, and the halogen atom may be substituted on a cyclic structure moiety, a side chain moiety, or both of these moieties. When the hydrocarbon group is substituted with two or more halogen atoms, these halogen atoms may be identical to or different from one another. Specific examples of the Ca-b halocycloalkyl include 2,2-difluorocyclopropyl, 2,2-dichlorocyclopropyl, 2,2-dibromocyclopropyl, 2,2-difluoro-1-methylcyclopropyl, 2,2-dichloro-1-methylcyclopropyl, 2,2-dibromo-1-methylcyclopropyl, and 2,2,3,3-tetrafluorocyclobutyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “benzyl” as used herein refers to “C6H5—CH2—.”
The expression “(Ca-b) alkyl substituted with R4”, “(Ca-b) alkyl substituted with R10”, “(Ca-b) alkyl substituted with R12”, “(Ca-b) alkyl substituted with R14”, “(Ca-b) alkyl substituted with R22”, “(Ca-b) alkyl substituted with R26”, “(Ca-b) alkyl substituted with R27”, “(Ca-b) alkyl substituted with R34”, “(Ca-b) alkyl substituted with R37”, “(Ca-b) alkyl substituted with R39”, “(Ca-b) alkyl substituted with R46”, or “(Ca-b) alkyl substituted with R47” as used herein refers to an alkyl group having a carbon atom number of a to b wherein any hydrogen atom bonded to a carbon atom is partially or completely substituted with one or more substituents R4, R10, R12, R14, R22, R26, R27, R34, R37, R39, R46, or R47, and the alkyl has the same meaning as defined above. Each group is selected within a range of the specified number of carbon atoms. When two or more substituents R4, R10, R12, R14, R22, R26, R27, R34, R37, R39, R46 or R47 are present, the substituents R4, R10, R12, R14, R22, R26, R27, R34, R37, R39, R46 or R47 may be identical to or different from one another.
The expression “(Ca-b) alkynyl substituted with R19” as used herein refers to an alkynyl group having a carbon atom number of a to b wherein any hydrogen atom bonded to a carbon atom is partially or completely substituted with one or more substituents R19, and the alkynyl has the same meaning as defined above. Each group is selected within a range of the specified number of carbon atoms. When two or more substituents R19 are present, the substituents R19 may be identical to or different from one another.
The expression “(Ca-b) cycloalkyl substituted with R44” or “(Ca-b) cycloalkyl substituted with R45” as used herein refers to a cycloalkyl group having a carbon atom number of a to b wherein any hydrogen atom bonded to a carbon atom is partially or completely substituted with one or more substituents R44 or R45, and the cycloalkyl has the same meaning as defined above. Each group is selected within a range of the specified number of carbon atoms. When two or more substituents R44 or R45 are present, the substituents R44 or R45 may be identical to or different from one another.
The expression “Ca-b cycloalkyl (Cd-e) alkyl” as used herein refers to an alkyl group having a carbon atom number of d to e and the same meaning as defined above wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a Ca-b cycloalkyl group having the same meaning as defined above. Each group is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkoxy (Cd-e) alkyl” as used herein refers to an alkyl group having a carbon atom number of d to e and the same meaning as defined above wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a Ca-b alkoxy group having the same meaning as defined above. Each group is selected within a range of the specified number of carbon atoms.
The expression “tri(Ca-b alkyl)silyl” as used herein refers to a silyl group substituted with alkyl groups having a carbon atom number of a to b and having the same meaning as defined above wherein the alkyl groups may be identical to or different from one another. Specific examples of the tri(Ca-b alkyl)silyl include trimethylsilyl, triethylsilyl, tri(n-propyl)silyl, ethyldimethylsilyl, n-propyldimethylsilyl, n-butyldimethylsilyl, i-butyldimethylsilyl, and tert-butyldimethylsilyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkylcarbonyl” as used herein refers to an alkyl-C(O)— group wherein the alkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b alkylcarbonyl include acetyl, n-propionyl, n-butyryl, i-butyryl, n-valeryl, i-valeryl, 2-methylbutanoyl, pivaloyl, n-hexanoyl, and n-heptanoyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkoxycarbonyl” as used herein refers to an alkyl-O—C(O)— group wherein the alkyl has the same meaning as defined above and has a carbon atom number of a to b. Specific examples of the Ca-b alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl, n-propyloxycarbonyl, i-propyloxycarbonyl, n-butoxycarbonyl, i-butoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, and 2-ethylhexyloxycarbonyl. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkylamino” as used herein refers to an amino group wherein one hydrogen atom is substituted with alkyl having the same meaning as defined above and having a carbon atom number of a to b. Specific examples of the Ca-b alkylamino include methylamino, ethylamino, n-propylamino, i-propylamino, n-butylamino, i-butylamino, and tert-butylamino. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b haloalkylamino” as used herein refers to an amino group wherein one hydrogen atom is substituted with haloalkyl having the same meaning as defined above and having a carbon atom number of a to b. Specific examples of the Ca-b haloalkylamino include 2,2,2-trifluoroethylamino, 2-chloro-2,2-difluoroethylamino, and 3,3,3-trifluoropropylamino. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “di(Ca-b) alkylamino” as used herein refers to an amino group wherein both hydrogen atoms are substituted with alkyl groups which have the same meaning as defined above and have a carbon atom number of a to b and which may be identical to or different from each other. Specific examples of the di(Cab) alkylamino include dimethylamino, ethyl(methyl)amino, diethylamino, n-propyl(methyl)amino, i-propyl(methyl)amino, di(n-propyl)amino, and di(n-butyl)amino. Each of these groups is selected within a range of the specified number of carbon atoms.
The expression “Ca-b alkylthio (Cd-e) alkyl” as used herein refers to an alkyl group having the same meaning as defined above and having a carbon atom number of d to e wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a Cab alkylthio group having the same meaning as defined above. Each group is selected within a range of the specified number of carbon atoms.
The expression “phenyl substituted with (Z2)p5a”, “phenyl substituted with (Z3)p5b”, or “phenyl substituted with (Z4)p5c” as used herein refers to a phenyl group wherein p5a, p5b, or p5c hydrogen atoms bonded to carbon atoms of the benzene ring are substituted with substituents Z2, Z3, or Z4 at any positions.
The expression “benzyl substituted with (Z4)p5c” as used herein refers to a benzyl group (C6H5—CH2—) wherein p5c hydrogen atoms bonded to carbon atoms of the benzene ring are substituted with substituents Z4 at any positions.
The production method of the present invention will next be described. In the following description, the symbol Ph denotes phenyl, and the symbol Bn denotes a benzyl group.
The compound of the present invention may include geometrical isomers (i.e., E-form and Z-form) depending on the types of substituents. In the following description, a mixture containing an E-form and a Z-form in any proportions is represented as a bond of a wavy line shown below.
The compound of the present invention of Formula (1) can be produced by, for example, any of the methods described below.
Production Method A
A compound of Formula (1) [wherein G, W1, X, R1, R2, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1)”] can be produced by reacting a compound of Formula (2) [wherein G, W1, X, R1, R2, Z1, and n have the same meanings as defined above, and J1 is a chlorine atom, a bromine atom, or an iodine atom] [hereinafter the compound will be referred to as “compound (2)”] with a compound of Formula (3) [wherein R3 has the same meaning as defined above] [hereinafter the compound will be referred to as “compound (3)”] or a compound of Formula (4) [wherein R3 has the same meaning as defined above] [hereinafter the compound will be referred to as “compound (4)”] in the presence of a palladium catalyst (e.g., palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), or [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride) in an amount of 0.001 to 0.5 equivalents by mole relative to compound (2) at a temperature ranging from room temperature to the reflux temperature of the reaction mixture for one hour to 48 hours, with optional use of a solvent (e.g., benzene, toluene, methanol, ethanol, propanol, 1,4-dioxane, tetrahydrofuran, dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, water, or a mixture containing two or more of these in any proportions), with optional use of a base (e.g., sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, or N,N-diisopropylethylamine) in an amount of 1 to 10 equivalents by mole relative to compound (2), and with optional addition of a ligand (e.g., triphenylphosphine, tricyclohexylphosphine, 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl, 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl, or 1,1′-bis(diphenylphosphino)ferrocene) in an amount of 0.001 to 0.5 equivalents by mole relative to compound (2).
Some of compounds (3) and compounds (4) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by known methods described in literature, for example, methods described in Japanese Unexamined Patent Application Publication No. 2002-47292 (JP 2002-47292 A), Tetrahedron, 2006, Vol. 62, page 2831, and European Journal of Organic Chemistry, 2009, Vol. 2009, No. 23, page 3964.
Production Method B
A compound of Formula (1-3) [wherein W1, X, R1, R2, R3, R5, Z1, same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-3)”], which is a type of compound (1) wherein G is —C(O)R5, can be produced by reacting a compound of Formula (1-1) [wherein W1, X, R1, R2, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-1)”], which is a type of compound (1) wherein G is a hydrogen atom, with a compound of Formula (5) [wherein R5 has the same meaning as defined above, and J2 is a chlorine atom, a bromine atom, a C1-4 alkylcarbonyloxy group (e.g., pivaloyl), a C1-4 alkoxycarbonyloxy group (e.g., isobutyloxycarbonyloxy), or an azolyl group (e.g., imidazol-1-yl)] [hereinafter the compound will be referred to as “compound (5)”] at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with optional use of a solvent (e.g., benzene, toluene, dichloromethane, chloroform, 1,2-dichloroethane, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, water, or a mixture containing two or more of these in any proportions), and optionally in the presence of a base (e.g., sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N,N-diisopropylethylamine, pyridine, or 4-(dimethylamino)pyridine) in an amount of 1 to 3 equivalents by mole relative to compound (1-1).
Some of compounds (5) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method C
A compound of Formula (1-4) [wherein W1, X, R1, R2. R3, R6, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-4)”], which is a type of compound (1) wherein G is —S(O)2R6, can be produced by reacting compound (1-1) with a compound of Formula (6) [wherein R6 has the same meaning as defined above, and J3 is a fluorine atom, a chlorine atom, a bromine atom, or —OS(O)2R6] [hereinafter the compound will be referred to as “compound (6)”] at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with optional use of a solvent (e.g., benzene, toluene, dichloromethane, chloroform, 1,2-dichloroethane, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, water, or a mixture containing two or more of these in any proportions), and optionally in the presence of a base (e.g., sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N,N-diisopropylethylamine, pyridine, or 4-(dimethylamino)pyridine) in an amount of 1 to 3 equivalents by mole relative to compound (1-1).
Some of compounds (6) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method D
A compound of Formula (1-2) [wherein G2, W1, X, R1, R2, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-2)”], which is a type of compound (1) wherein G is G2, can be produced by reacting compound (1-1) with a compound of Formula (7) [wherein G2 is C1-6 alkyl or (C1-6) alkyl substituted with R4; J4 is a chlorine atom, a bromine atom, an iodine atom, C1-6 alkylsulfonyloxy, or C1-6 haloalkylsulfonyloxy; and R4 has the same meaning as defined above] [hereinafter the compound will be referred to as “compound (7)”] at a temperature ranging from −78° C. to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with optional use of a solvent (e.g., benzene, toluene, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, sulfolane, triamide hexamethylphosphate, water, or a mixture containing two or more of these in any proportions), and optionally in the presence of a base (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, potassium hydride, potassium tert-butoxide, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, or lithium bis(trimethylsilyl)amide) in an amount of 1 to 3 equivalents by mole relative to compound (1-1).
Some of compounds (7) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method E
A compound of Formula (1b) [wherein G, X, R1, R2, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1b)”], which is a type of compound (1) wherein W1 is a sulfur atom, can be produced by reacting a compound of Formula (1a) [wherein G, X, R1, R2, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1a)”], which is a type of compound (1) wherein W1 is an oxygen atom, with diphosphorus pentasulfide or Lawesson's reagent: 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide] in an amount of 1 to 10 equivalents by mole relative to compound (1a) at a temperature ranging from room temperature to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with optional use of a solvent (e.g., benzene, toluene, xylene, pyridine, piperidine, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, or a mixture containing two or more of these in any proportions).
Compound (1-1a) can be produced by the method described below.
Production Method F
A compound of Formula (1-1a) [wherein X, R1, R2, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-1a)”], which is a type of compound (1-1) wherein W1 is an oxygen atom, can be produced by reacting a compound of Formula (8) [wherein X, R1, R2, R3, Z1, and n have the same meanings as defined above, and Rx is C1-6 alkyl] [hereinafter the compound will be referred to as “compound (8)”] at a temperature ranging from room temperature to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with optional use of a solvent (e.g., hexane, heptane, benzene, toluene, diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, acetone, methyl ethyl ketone, acetonitrile, water, or a mixture containing two or more of these in any proportions), and optionally in the presence of a base (e.g., triethylamine, tributylamine, diisopropylethylamine, pyridine, 4-(dimethylamino)pyridine, 1,8-diazabicyclo[5,4,0]-7-undecene, 1,4-diazabicyclo[2,2,2]octane, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, or potassium tert-butoxide) in an amount of 1 to 5 equivalents by mole relative to compound (8).
Production Method G
Compound (1-1) can be produced by reacting compound (1-2) with morpholine in an amount of 1 to 20 equivalents by mole relative to compound (1-2) at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for one hour to 48 hours, with optional use of a solvent (e.g., benzene, toluene, xylene, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, sulfolane, acetonitrile, water, or a mixture containing two or more of these in any proportions); or reacting compound (1-2) with a protonic acid (e.g., sulfuric acid or hydrochloric acid) or a Lewis acid (e.g., boron bromide, aluminum chloride, or zinc chloride) in an amount of 1 to 100 equivalents by mole relative to compound (1-2) at a temperature ranging from −78° C. to the reflux temperature of the reaction mixture for one hour to 48 hours, with optional use of a solvent (e.g., dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride, or a mixture containing two or more of these in any proportions); or reacting compound (1-2) with a base (e.g., sodium hydroxide, potassium hydroxide, or lithium hydroxide) in an amount of 1 to 20 equivalents by mole relative to compound (1-2) at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for one hour to 48 hours, with optional use of a solvent (e.g., methanol, ethanol, normal propanol, isopropanol, normal butanol, 1,4-dioxane, 1,2-dimethoxyethane, tetrahydrofuran, water, or a mixture containing two or more of these in any proportions).
Production Method H
Compound (1-1) can be produced by reacting compound (1-3) with sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, or sodium ethoxide in an amount of 1 to 5 equivalents by mole relative to compound (1-3) at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for one hour to 48 hours, with optional use of a solvent (e.g., methanol, ethanol, benzene, toluene, tetrahydrofuran, 1,4-dioxane, acetonitrile, acetone, water, or a mixture containing two or more of these in any proportions).
Production Method I
A compound of Formula (1-5) [wherein W1, X, G, R1, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-5)”], which is a type of compound (1) wherein R2 is a hydrogen atom, can be produced by reacting a compound of Formula (1-6) [wherein W1, X, G, R1, R3, J1, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-6)”], which is a type of compound (1) wherein R2 is J1-, in a hydrogen atmosphere at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for 30 minutes to 50 hours in the presence of a palladium carbon catalyst in an amount of 0.1 to 3 parts by mass relative to compound (1-6), with use of a solvent (e.g., methanol, ethanol, benzene, toluene, 1,4-dioxane, tetrahydrofuran, dimethoxyethane, ethyl acetate, acetonitrile, N,N-dimethylformamide, acetic acid, water, or a mixture containing two or more of these in any proportions), and with optional use of an acid (e.g., hydrochloric acid, sulfuric acid, or methanesulfonic acid) or a base (e.g., triethylamine, N,N-diisopropylethylamine, or pyridine).
Production Method J
A compound of Formula (1-6) [wherein X, G, R1, R3, Z1, n, and J1 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-6)”], which is a type of compound (1) wherein R2 is J1, can be produced by reacting a compound of Formula (1-7) [wherein W1, X, G, R1, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-7)”], which is a type of compound (1) wherein R2 is —NH2, with sodium nitrite (9) or a compound of Formula (10) [wherein J5 is C3-6 alkyl] [hereinafter the compound will be referred to as “compound (10)”] in an amount of 0.5 to 5 equivalents by mole relative to compound (1-7) and a compound of Formula (11) [wherein J1 has the same meaning as defined above] [hereinafter the compound will be referred to as “compound (11)”] at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with optional use of, for example, copper chloride, copper bromide, copper iodide, or potassium iodide, and with use of a solvent (e.g., methanol, ethanol, 1,4-dioxane, tetrahydrofuran, acetonitrile, dichloromethane, N,N-dimethylformamide, water, or a mixture containing two or more of these in any proportions).
Compounds (9), (10), and (11) used herein are known compounds and some of them are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method K
Compound (1-7) can be produced by reacting a compound of Formula (1-8) [wherein X, G, R1, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-8)”], which is a type of compound (1) wherein R2 is —N(Bn)2, in a hydrogen atmosphere at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for 30 minutes to 100 hours in the presence of a palladium carbon catalyst in an amount of 0.1 to 3 parts by mass relative to compound (1-8), with use of a solvent (e.g., methanol, ethanol, benzene, toluene, 1,4-dioxane, tetrahydrofuran, dimethoxyethane, ethyl acetate, acetonitrile, N,N-dimethylformamide, acetic acid, water, or a mixture containing two or more of these in any proportions), and with optional addition of an acid catalyst (e.g., hydrochloric acid, sulfuric acid, or methanesulfonic acid).
Production Method L
A compound of Formula (1-10) [wherein W1, G, X, R1, R2, and R3 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-10)”], which is a type of compound (1) wherein Z1 is a hydroxy group, can be produced by reacting a compound of Formula (1-9) [wherein W1, G, X, R1, R2, and R3 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-9)”], which is a type of compound (1) wherein at least one Z1 is —OBn, in a hydrogen atmosphere at a temperature ranging from 0° C. to the reflux temperature of the reaction mixture for 30 minutes to 50 hours in the presence of a palladium carbon catalyst in an amount of 0.1 to 3 parts by mass relative to compound (1-9), with use of a solvent (e.g., methanol, ethanol, benzene, toluene, 1,4-dioxane, tetrahydrofuran, dimethoxyethane, ethyl acetate, acetonitrile, N,N-dimethylformamide, acetic acid, water, or a mixture containing two or more of these in any proportions), and with optional use of an acid (e.g., hydrochloric acid, sulfuric acid, or methanesulfonic acid) or a base (e.g., triethylamine, N,N-diisopropylethylamine, or pyridine). Subsequently, a compound of Formula (1-11) [wherein G, X, R1, R2, R3, and R35a have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-11)”] can be produced by reacting compound (1-10) with a compound of Formula (12) [wherein J4 has the same meaning as defined above, and R35a corresponds to substituents represented by R35 (except for a hydrogen atom)] [hereinafter the compound will be referred to as “compound (12)”] at a temperature ranging from room temperature to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with use of a solvent (e.g., tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, acetone, methyl ethyl ketone, acetonitrile, water, or a mixture containing two or more of these in any proportions), and in the presence of a base (e.g., sodium hydroxide, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, potassium hydride, potassium tert-butoxide, triethylamine, tributylamine, diisopropylethylamine, pyridine, 4-(dimethylamino)pyridine, or 1,8-diazabicyclo[5,4,0]-7-undecene) in an amount of 1 to 5 equivalents by mole relative to compound (1-10).
Some of compounds (12) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method M
A compound of Formula (1-13) [wherein W1, Z1, X, G, n, R1, R2, and R3 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-13)”], which is a type of compound (1) wherein at least one Y1 is a hydroxy group, can be produced by reacting a compound of Formula (1-12) [wherein W1, Z1, X, G, n, R1, R2, and R3 have the same meanings as defined above; note: BnO—, HO—, and R11aO— are originally included in R3, but are shown in the Formulae separately from R3 for the sake of convenience and clarity] [hereinafter the compound will be referred to as “compound (1-12)”], which is a type of compound (1) wherein at least one Y1 in R3 is —OBn, under the same conditions as in production method L. Subsequently, a compound of Formula (1-14) [wherein W1, Z1, X, G, n, R1, R2, R3, and R11a have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-14)”], which is a type of compound (1) wherein at least one Y1 is —OR11a can be produced by reacting compound (1-13) with a compound of Formula (13) [wherein J4 has the same meaning as defined above, and R11a corresponds to substituents represented by (except for a hydrogen atom)] [hereinafter the compound will be referred to as “compound (13)”] in the same manner as in production method L.
Some of compounds (13) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method N
A compound of Formula (1-16) [wherein W1, G, X, R1, R2, and R3 have the same meanings as defined above, and Z1b is —NR15R16 or —N═C(C6H5)2] [hereinafter the compound will be referred to as “compound (1-16)”], which is a type of compound (1) wherein at least one Z1 is —NR15R16 or —N═C(C6H5)2, can be produced by reacting a compound of Formula (1-15) [wherein W1, X, G, R1, R2, and R3 have the same meanings as defined above, and Z1a is a chlorine atom, a bromine atom, an iodine atom, C1-6 alkylsulfonyloxy or C1-6 haloalkylsulfonyloxy] [hereinafter the compound will be referred to as “compound (1-15)”], which is a type of compound (1) wherein at least one Z1 is Z1a, with a compound of Formula (14) [wherein R15 and R16 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (14)”] or benzophenoneimine (15) through a method described in, for example, International Publication WO 2013/033228 or WO 2016/102420 in the presence of a palladium catalyst.
Some of compounds (14) and (15) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method 0
A compound of Formula (1-17) [wherein W1, X, G, R1, R2, R3, and Z1c have the same meanings as defined above], which is a type of compound (1) wherein at least one Z1 is Z1c, can be produced by reacting compound (1-15) with a compound of Formula (16) [wherein Z1c is phenyl, phenyl substituted with (Z4)p5c, Q-2, Q-3, Q-4, Q-5, or C3-6 cycloalkyl] or a compound of Formula (17) [wherein Z1c has the same meaning as defined above] through a method described in, for example, International Publication WO 2019/178129 or Angewandte Chemie, International Edition, 2018, Vol. 57, page 14198 in the presence of a palladium catalyst.
Some of compounds (16) and (17) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method P
A compound of Formula (1-18) [wherein W1, X, G, R1, R2, R3, and Ra have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-18)”] can be produced by reacting compound (1-15) with a compound of Formula (18) [wherein Ra is C1-4 alkyl, C3-6 cycloalkyl, or tri(C1-6 alkyl)silyl] [hereinafter the compound will be referred to as “compound (18)”] through a method described in, for example, The Journal of Organic Chemistry, 2007, Vol. 72, page 6672.
Some of compounds (18) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method Q
A compound of Formula (1-19) [wherein W1, X, G, R1, R2, R3, and R36a have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-19)”], which is a type of compound (1) wherein at least one Z1 is —SR36a, can be produced by reacting compound (1-15) with a compound of Formula (19) [wherein R36a is C1-6 haloalkyl] [hereinafter the compound will be referred to as “compound (19)”] through a method described in, for example, U.S. Patent Application Publication No. 6215021.
Some of compounds (19) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Production Method R
A compound of Formula (1-20) [wherein W1, X, G, R1, R2, R3, and Ry have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-20)”] is prepared by reacting compound (1-15) with a compound of Formula (20) [wherein Ry is C1-10 alkyl] [hereinafter the compound will be referred to as “compound (20)”] through a method described in, for example, International Publication WO 2016/044770 in the presence of a palladium catalyst. Subsequently, a compound of Formula (1-21) [wherein X, G, R1, R2, R3, and R36 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (1-21)”], which is a type of compound (1) wherein at least one Z1 is —SR36, can be produced by reacting compound (1-20) with a compound of Formula (20) [wherein R36 and J4 have the same meanings defined above] [hereinafter the compound will be referred to as “compound (20)”] in the presence of a base (e.g., sodium methoxide, sodium ethoxide, or potassium tert-butoxide) in an amount of 1 to 20 equivalents by mole relative to compound (1-20).
Some of compounds (20) and (21) used herein are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
In production methods A to R, the reaction mixture after completion of the reaction can be subjected to a common post-treatment (e.g., direct concentration; or dissolution in an organic solvent, washing with water, and subsequent concentration; or addition into ice water, extraction with an organic solvent, and subsequent concentration), to thereby yield a pyridazinone compound of interest. When purification is required, the reaction mixture can be purified through separation of impurities by any purification technique, such as recrystallization, column chromatography, thin-layer chromatography, or preparative liquid chromatography.
Compound (2) used in production method A can be synthesized as shown in, for example, reaction scheme 1.
Compound (2) can be produced by reacting a compound of Formula (21) [wherein W1, G, R1, R2, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (21)”] with a compound of Formula (22) [wherein J1 has the same meaning as defined above] [hereinafter the compound will be referred to as “compound (22)”] or a compound of Formula (23) [wherein J1 has the same meaning as defined above] [hereinafter the compound will be referred to as “compound (23)”] through a method described in, for example, Chemistry of Heterocyclic Compounds, 2017, Vol. 53, page 1156.
Some of compounds (21) used in reaction scheme 1 are known compounds and can be synthesized by a method described in literature, for example, a method described in International Publication WO 2015/168010 or WO 2017/074992.
Compound (22) or (23) used in reaction scheme 1 is also a known compound and is available as a commercial product.
Compound (8) used in production method F can be synthesized as shown in reaction scheme 2 or 3, and compound (8-1a), which is a type of compound (8) wherein R1 is R1a, can be synthesized as shown in reaction scheme 4.
A compound of Formula (26) [wherein X, R3, Z1, n, and J6 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (26)”] is prepared by reacting a compound of Formula (24) [wherein X, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (24)”] with a compound of Formula (25) [wherein J6 is pentafluorophenyl or 2,4,6-trichlorophenyl] [hereinafter the compound will be referred to as “compound (25)”] through a method described in, for example, International Publication WO 2017/074992 with use of a condensing agent such as N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride. Subsequently, a compound of Formula (28) [wherein X, R1, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (28)”] can be produced by reacting compound (26) with a hydrazine derivative of Formula (27) [wherein R1 has the same meaning as defined above] or a salt thereof [e.g., hydrochloride, bromate, or sulfate, hereinafter referred to as “compound (27)”]. Subsequently, compound (8) can be produced by reacting compound (28) with a compound of Formula (29) [wherein R2 and Rx have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (29)”].
Some of compounds (25), (27), and (29) used in reaction scheme 2 are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
A compound of Formula (32) [wherein X, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (32)”] is prepared by reacting compound (24) with oxalyl chloride (30) or thionyl chloride (31) in an amount of 1 to 20 equivalents by mole relative to compound (24) at 0° C. to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with optional use of a solvent (e.g., dichloromethane, chloroform, 1,2-dichloroethane, toluene, xylene, or a mixture containing two or more of these in any proportions), and with optional addition of N,N-dimethylformamide. Subsequently, compound (8) can be produced by reacting compound (32) with a compound of Formula (33) [wherein R1, R2, and Rx have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (33)”] at 0° C. to the reflux temperature of the reaction mixture for 30 minutes to 24 hours, with use of a solvent (e.g., dichloromethane, chloroform, 1,2-dichloroethane, pyridine, toluene, xylene, ethyl acetate, butyl acetate, heptane, 2-butanone, water, or a mixture containing two or more of these in any proportions), and optionally in the presence of a base (e.g., triethylamine, diisopropylethylamine, pyridine, 4-dimethylaminopyridine, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, cesium carbonate, sodium hydroxide, or potassium hydroxide).
Some of compounds (33) used herein are known compounds, and the other compounds can also be synthesized by synthesis methods for known compounds; for example, a method described in Nature Communications, 2017, Vol. 8, page 1 or International Publication WO 2012/091156.
A compound of Formula (8-1a) [hereinafter the compound will be referred to as “compound (8-1a)”], which is a type of compound (8) wherein R1 is R1a, can be synthesized by reacting a compound of Formula (8-1) [hereinafter the compound will be referred to as “compound (8-1)”], which is a type of compound (8) wherein R1 is a hydrogen atom, with a compound of Formula (34) [wherein R1a is C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, or C1-6 alkyl substituted with R34, and R34 and J4 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (34)”] through a method described in, for example, Advanced Synthesis & Catalysis, 2016, Vol. 358, page 276.
Compound (8-1) used herein can be synthesized by the method shown in reaction scheme 2 or 3. Some of compounds (34) are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
Some of compounds (24) used in reaction schemes 2 and 3 are known compounds and are available as commercial products. The other compounds can be synthesized by a method shown in, for example, reaction scheme 5, 6, or 7.
A compound of Formula (36) [wherein X, Rx, Z1, J1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (36)”] can be produced by reacting a compound of Formula (35) [wherein X, Rx, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (35)”] with compound (22) or compound (23) in the same manner as shown in reaction scheme 1. Subsequently, a compound of Formula (37) [wherein X, R3, Rx, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (37)”] can be produced by reacting with compound (36) with compound (3) or compound (4) in the same manner as in production method A. Subsequently, compound (24) can be produced by reacting compound (37) with an aqueous solution of an alkali metal (e.g., sodium hydroxide, potassium hydroxide, or lithium hydroxide) through a method described in, for example, International Publication WO 2013/009259.
Some of compounds (35) used in reaction scheme 5 are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds. The synthesis method for known compounds is described in, for example, Der Pharma Chemica, 2017, Vol. 9, page 85 and Organic Letters, 2008, Vol. 10, page 573.
A compound of Formula (37-1) [wherein X, Z1, R3, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (37-1)”], which is a type of compound (37) wherein Rx is methyl, can be produced by reacting a compound of Formula (38) [wherein X, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (38)”] with a compound of Formula (39) [wherein R3 and J1 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (39)”] in the presence of a palladium catalyst, and by treating the reaction mixture with methyl iodide and potassium carbonate through a synthesis method for a known compound; for example, a method described in Chemistry Letters, 2011, Vol. 40, page 1015. Subsequently, compound (24) can be produced through hydrolysis of compound (37-1) in the same manner as shown in reaction scheme 5.
Some of compounds (38) used in reaction scheme 6 are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds. The synthesis method for known compounds is described in, for example, Heterocycles, 1995, Vol. 41, page 647.
Some of compounds (39) are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
A compound of Formula (42) [wherein X, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (42)”] can be produced by reacting a compound of Formula (40) [wherein Z1 and n have the same meanings as defined above, and J7 is a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom] [hereinafter the compound will be referred to as “compound (40)”] with a compound of Formula (41) [wherein X and R3 have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (41)”] in the presence of a base (e.g., sodium hydroxide, potassium hydroxide, sodium carbonate, or potassium carbonate) through a synthesis method for a known compound; for example, a method described in Tetrahedron Letters, 2003, Vol. 44, page 6665. Subsequently, a compound of Formula (46) [wherein X, R3, J1, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (46)”] can be produced by reacting compound (42) with a formaldehyde equivalent such as 1,3,5-trioxane (43), paraformaldehyde (44), or with formaldehyde (45) in the presence of compound (11) through a method described in, for example, Journal of the American Chemical Society, 1948, Vol. 70, page 3768. Subsequently, a compound of Formula (49) [wherein X, R3, Z1, and n have the same meanings as defined above] [hereinafter the compound will be referred to as “compound (49)”] can be produced by reacting compound (46) with a compound of Formula (47) [wherein J8 is methyl or ethyl] [hereinafter the compound will be referred to as “compound (47)”] or a compound of Formula (48) [wherein M is an alkali metal such as sodium or potassium] [hereinafter the compound will be referred to as “compound (48)”] through a method described in, for example, Journal of Heterocyclic Chemistry, 1965, Vol. 2, page 231. Subsequently, compound (24) can be produced by reacting compound (49) with an aqueous solution of an alkali metal (e.g., sodium hydroxide, potassium hydroxide, or lithium hydroxide) or an acidic compound (e.g., hydrochloric acid, sulfuric acid, or acetic acid) through a method described in, for example, International Publication WO 2002/016353.
Some of compounds (40), (41), (47), and (48) used in reaction scheme 7 are known compounds and are available as commercial products. The other compounds can also be synthesized by synthesis methods for known compounds.
A production intermediate serving as a raw material compound for each of reaction schemes 1 to 7 can be produced by performing a common post-treatment after completion of the aforementioned reaction.
Each of the production intermediates produced by such a method can be used for the reaction in the subsequent step without isolation or purification.
Examples of the pyridazinone compound of Formula (1) of the present invention, which can be produced by any of the aforementioned methods, include compounds shown in Table 1. However, Table 1 is merely provided for illustration, and the pyridazinone compound of the present invention is not limited to examples shown in Table 1.
In Table 1, Me denotes methyl; Et, ethyl; n-Pr or Pr-n, normal propyl; i-Pr or Pr-i, isopropyl; c-Pr or Pr-c, cyclopropyl; n-Bu or Bu-n, normal butyl; i-Bu or Bu-i, isobutyl; sec-Bu or Bu-sec, secondary butyl; tert-Bu or Bu-tert, tertiary butyl; c-Bu or Bu-c, cyclobutyl; c-Pen or Pen-c, cyclopentyl; and c-Hex or Hex-c, cyclohexyl.
In Table 1, D-1 to D-56 correspond to the following structures.
In Table 1, U-1a to U-32a, T-1-1 to T-1-5, and Q-1-1 to Q-35-1 correspond to the following structures.
The expression “(Y1)” in Table 1 refers to (Y1)p7, (Y1)p6, (Y1)p5, (Y1)P4, (Y1)P3, or (Y1)P2 corresponding to each of the aforementioned structures of D-1 to D-56 specified in the column of R3. The substitution position number corresponds to the numbered position in each of the aforementioned structural formulae. The expression “-” in the column of (Z1)n and “(Y1)” refers to no substitution.
Table 1-2 has the same structure as Table 1, except that the condition of Table 1 (i.e., R1 is Me, R2 is Me, W1 is O, G is H, X is S, and (Z1) is “-” (no substitution)) is replaced with the following condition (i.e., R1 is Me, R2 is Me, W1 is O, G is Me, X is O, and (Z1)n is “-” (no substitution)).
Specifically, the “condition” described in Table 1-2 of Table 2 corresponds to a compound of Formula (1) wherein R1 is methyl, R2 is methyl, W1 is an oxygen atom, G is methyl, X is 0, (Z1) is “-” (i.e., n is 0, and the substituent Z1 is not present), R3 is D-1, and (Y1) is “-” (no substitution). The same shall apply to Tables 1-3 to 1-1342.
The compound of the present invention can be used as a herbicide for paddy fields in both soil treatment and foliage treatment under submerged conditions. Examples of paddy field weeds include Gramineae weeds, such as chinese sprangletop (Leptochloa chinensis), bearded sprangletop (Leptochloa fascicularis), barnyard grass (Echinochloa crus-galli), junglerice (Echinochloa colonum), late watergrass (Echinochloa oryzicola), southern cutgrass (Leersia hexandra), knotgrass (Paspalum distichum) saramollagrass (Ischaemum rugosum), itchgrass (Rottboellia cochinchinensis), broadleaf signalgrass (Brachiaria platyphylla), Alexandergrass (Brachiaria plantaginea), large crabgrass (Digitaria sanguinalis), crowfoot grass (Dactyloctenium aegyptium), goosegrass (Eleusine indica), red rice (Oryza sativa), bermuda grass (Cynodon dactylon), and fall panicum (Panicum dichotomiflorum); Cyperaceae weeds, such as Eleocharis kuroguwai, globe fringerush (Fimbristylis miliacea), Japanese bulrush (Schoenoplectus juncoides), Schoenoplectus nipponicus, ricefield bulrush (Schoenoplectus mucronatus), Cyperus serotinus, smallflower umbrella sedge (Cyperus difformis), rice flat sedge (Cyperus iria), purple nutsedge (Cyperus rotundus), yellow nutsedge (Cyperus esculentus), and cosmopolitan bulrush (Bolboschoenus martimus); Alismataceae weeds, such as water plantain (Alisma canaliculatum), pygmy arrowhead (Sagittaria pygmaea), and threeleaf arrowhead (Sagittaria trifolia); Commelinaceae weeds, such as asian spiderwort (Murdannia keisak) and benghal dayflower (Commelina benghalensis); Pontederiaceae weeds, such as heartleaf false pickerelweed (Monochoria korsakowii), oval-leafed pondweed (Monochoria vaginalis), ducksalad (Heteranthera limosa), and water hyacinth (Eichhornia crassipes); Elatinaceae weeds, such as threestamen waterwort (Elatine triandra); Lythraceae weeds, such as redstem (Ammannia coccinea) and indian toothcup (Rotala indica); Oenotheraceae weeds, such as Ludwigia epilobioides and mexican primrose-willow (Ludwigia octovalvis); Scrophulariaceae weeds, such as rushlike dopatrium (Dopatrium junceum), Gratiola japonica, dwarf ambulia (Limnophila sessiliflora), prostrate false pimpernel (Lindernia pyxidaria), and yellowseed false pimpernel (Lindernia dubia); Amaranthaceae weeds, such as alligator weed (Alternanthera philoxeroides) and spiny amaranth (Amaranthus spinosus); Polygonaceae weeds, such as water pepper (Polygonum hydropiper); Sphenocleaceae weeds, such as gooseweed (Sphenoclea zeylanica); Fabaceae weeds, Indian jointvetch (Aeschynomene indica) and hemp sesbania (Sesbania exaltata); Asteraceae weeds, such as devil's beggarticks (Bidens frondosa), three-lobe beggarticks (Bidens tripartita), false daisy (Eclipta prostrata), and goatweed (Ageratum conyzoides); Convolvulaceae weeds, such as swamp morningglory (Ipomoea aquatica); Marsileaceae weeds, such as water clover (Marsilea minuta); Lemnaceae weeds, such as common duckmeat (Spirodela polyrhiza) and duckweed (Lemna paucicostata); and Potamogetonaceae weeds, such as roundleaf pondweed (Potamogeton distinctus).
When the composition of the present invention is used in paddy fields, the treatment can be performed before and after rice planting in a usual manner, and can also be performed in parallel with rice planting.
The compound of the present invention can also be used as a herbicide for farmlands and orchards in any of soil treatment, soil incorporation treatment, and foliage treatment. Examples of farmland weeds include Poaceae weeds, such as fall panicum (Panicum dichotomiflorum), shattercane (Sorgham bicolor), Johnson grass (Sorghum halepense), barnyard grass (Echinochloa crus-galli var crus-galli), cockspur grass (Echinochloa crus-galli var. praticola), Japanese barnyard millet (Echinochloa utilis), southern crabgrass (Digitaria ciliaris), sourgrass (Digitaria insularis), Jamaican crabgrass (Digitaria horizontalis), wild oat (Avena fatua), blackgrass (Alopecurus myosuroides), shortawn foxtail (Alopecurus aequalis), windgrass (Apera spica-venti), downy brome (Bromus tectorum), Italian ryegrass (Lolium multiflorum), rigid ryegrass (Lolium rigidum), littleseed canarygrass (Phalaris minor), annual bluegrass (Poa annua), goosegrass (Eleusine indica), green foxtail (Setaria viridis), giant foxtail (Setaria faberi), signalgrass (Brachiaria decumbens), and southern sandbur (Cenchrus echinatus); Cyperaceae weeds, such as purple nutsedge (Cyperus rotundus); Solanaceae weeds, such as black nightshade (Solanum nigrum) and jimsonweed (Datura stramonium); Malvaceae weeds, velvetleaf (Abutilon theophrasti) and prickly sida (Sida spinosa); Convolvulaceae weeds, such as tall morning-glory (Ipomoea purpurea), ivyleaf morning-glory (Ipomoea hederacea), and Japanese bindweed (Calystegia hederacea); Amaranthaceae weeds, such as purple amaranth (Amaranthus lividus), redroot pigweed (Amaranthus retroflexus), palmer amaranth (Amaranthus palmeri), and tall waterhemp (Amaranthus tuberculatus); Asteraceae weeds, such as common cocklebur (Xanthium strumarium), common ragweed (Ambrosia artemisiifolia), giant ragweed (Ambrosia trifida), horseweed (Conyza canadensis), common sunflower (Helianthus annuus), pineappleweed (Matricaria matricarioides), hairy galinsoga (Galinsoga ciliata), Canada thistle (Cirsium arvense), common groundsel (Senecio vulgaris), and annual fleabane (Erigeron annuus); Brassicaceae weeds, such as variable leaf yellowcress (Rorippa indica), wild mustard (Sinapis arvensis), and shepherd's purse (Capsella bursa pastoris); Polygonaceae weeds, such as oriental lady's thumb (Persicaria longiseta) and wild buckwheat (Polygonum convolvulus); Portulacaceae weeds, such as common purslane (Portulaca oleracea); Chenopodiaceae weeds, such as lamb squarters (Chenopodium album), figleaved goosefoot (Chenopodium ficifolium), kochia (Kochia scoparia), and Russian thistle (Salsola tragus); Caryophyllaceae weeds, such as common chickweed (Stellaria media); Plantaginaceae weeds, such as Persian speedwell (Veronica persica); Commelinaceae weeds, such as Asiatic dayflower (Commelina communis) and Benghal dayflowe (Commelina benghalensis); Lamiaceae weeds, such as henbit (Lamium amplexicaule) and purple deadnettle (Lamium purpureum); Euphorbiaceae weeds, such as wild poinsettia (Euphorbia heterophylla) and spotted spurge (Euphorbia maculata); Rubiaceae weeds, such as false cleavers (Galium spurium) and Asian madder (Rubia akane); Violaceae weeds, such as pansy (Viola tricolor); Papaveraceae weeds, such as filed poppy (Papaver rhoeas); Fabaceae weeds, such as hemp sesbania (Sesbania exaltata) and sicklepod (Cassia obtusifolia); and Oxalidaceae weeds, such as creeping woodsorrel (Oxalis corniculata).
The compound of the present invention can be used for any of soil treatment, soil incorporation treatment, and foliage treatment in non-agricultural lands such as turfs, play grounds, open grounds, road sides, and line ends, other than the agricultural and horticultural fields, such as paddy fields, farmlands, and orchards. Examples of the weeds in these non-agricultural lands include, besides the aforementioned weeds in farmlands and orchards, annual bluegrass (Poa annua), dandelion (Taraxacum officinale), hairy fleabane (Conyza bonariensis), horseweed (Conyza canadensis), guernsey fleabane (Conyza sumatrensis), wavy bittercress (Cardamine flexuosa), white clover (Trifohum repens), lawn pennywort (Hydrocotyle sibthorpioides), Chinese plantain (Plantago asiatica), green kyllinga (Kyllinga brevifolia), and field horsetail (Equisetum arvense).
The composition of the present invention can be applied to a useful plant, a place where the useful plant is to be grown or where it is growing, or a non-agricultural land in a simultaneous or separate manner, to thereby control the growth of an unwanted plants relative to the useful plant. The aforementioned useful plant encompasses, for example, a field crop or a paddy crop, a horticultural crop, turf, and a fruit tree.
Specific examples of the term “useful plant” as used herein include, but are not limited to, crops, such as corn, rice, wheat, barley, rye, oat, sorghum, cotton, soybean, peanut, buckwheat, beet, rapeseed, sunflower, sugar cane, and tobacco; vegetables, such as solanaceous vegetables (e.g., eggplant, tomato, pepper, capsicum, and potato), cucurbitaceous vegetables (e.g., cucumber, pumpkin, zucchini, watermelon, and melon), brassicaceous vegetables (e.g., radish, turnip, horseradish, kohlrabi, Chinese cabbage, cabbage, mustard, broccoli, and cauliflower), Asteraceous vegetables (e.g., burdock, garland chrysanthemum, artichoke, and lettuce), liliaceae vegetables (e.g., leek, onion, garlic, and asparagus), ammiaceous vegetables (e.g., carrot, parsley, celery, and parsnip), chenopodiaceous vegetables (e.g., spinach and Swiss chard), labiatae vegetables (e.g., beefsteak plant, mint, and basil), strawberry, sweet potato, Japanese yam, and aroid; fruits, such as pomaceous fruits (e.g., apple, pear, Japanese pear, quince, and marmelo), stone fleshy fruits (e.g., peach, plum, nectarine, Japanese apricot, cherry, apricot, and prune), citrus fruits (e.g., Citrus unshiu, orange, lemon, lime, and grapefruit), nuts (e.g., chestnut, walnut, hazelnut, almond, pistachio, cashew nut, and macadamia nut), berry fruits (e.g., blueberry, cranberry, blackberry, and raspberry), grape, persimmon, olive, loquat, banana, coffee, date palm, coconut, and oil palm; trees other than fruit trees, such as tea, mulberry, street trees (e.g., ash, birch, dogwood, eucalyptus, ginkgo, lilac, maple, oak, poplar, cercis, liquidambar, plane, zelkova, Japanese arborvitae, Japanese fir, hemlock, juniper, pine, spruce, yew, elm, and buckeye), sweet viburnum, shrubby Japanese yew, cedar, cypress, croton, Japanese spindle, and Japanese photinia; turfs, such as Korean lawn grass (e.g., Zoysia japonica, and Zoysia tenuifolia), Bermuda grass (e.g., Cynodon dactylon), bent grass (e.g., creeping bent, Agrostis stolonifera, and Agrostis capillaris), bluegrass (e.g., Kentucky bluegrass and rough bluegrass), fescue (e.g., Festuca arundinacea, Festuca rubra var. commutate, and creeping red fescue), ryegrass (e.g., darnel, rye grass, and Italian grass), cocksfoot, and timothy grass; oil crops, such as oil palm and Jatropha curcas; flowers and ornamental plants (e.g., rose, carnation, chrysanthemum, prairie gentian, gypsophila, gerbera, marigold, salvia, petunia, verbena, tulip, aster, gentian, lily, pansy, cyclamen, orchid, lily of the valley, lavender, stock, ornamental cabbage, primrose, poinsettia, gladiolus, cattleya, daisy, verbena, cymbidium, and begonia); and foliage plants.
Examples of the term “useful plant” as used herein also include plants that are provided with resistance to HPPD inhibitors (e.g., isoxaflutole), ALS inhibitors (e.g., imazethapyr and thifensulfuron-methyl), EPSP synthase inhibitors (e.g., glyphosate), glutamine synthase inhibitors (e.g., glufosinate), acetyl-CoA carboxylase inhibitors (e.g., sethoxydim), PPO inhibitors (e.g., flumioxazin), and herbicides (e.g., bromoxynil, dicamba, and 2,4-D) by a classical breeding method and a genetic transformation technique.
Examples of the “agricultural and horticultural plant” provided with resistance by a classical breeding method include rapeseed, wheat, sunflower, rice, and corn exhibiting resistance to an imidazolinone-based ALS inhibitory herbicide (e.g., imazethapyr), which are already commercially available under a trade name of Clearfield <registered trademark>.
Similarly, there is soybean provided with resistance to a sulfonylurea-based ALS inhibitory herbicide (e.g., thifensulfuron-methyl) by a classical breeding method, which is already commercially available under a trade name of STS soybean. Similarly, examples of the agricultural and horticultural plant provided with resistance to an acetyl-CoA carboxylase inhibitor (e.g., trione oxime or aryloxy phenoxypropionic acid herbicide) by a classical breeding method include SR corn. The agricultural and horticultural plant provided with resistance to an acetyl-CoA carboxylase inhibitor is described in, for example, Proceedings of the National Academy of Sciences of the United States of America (Proc. Natl. Acad. Sci. USA), Vol. 87, pp. 7175-7179 (1990). A variant acetyl-CoA carboxylase resistant to an acetyl-CoA carboxylase inhibitor is reported in, for example, Weed Science, Vol. 53, pp. 728-746 (2005) and a plant resistant to an acetyl-CoA carboxylase inhibitor can be generated by introducing the gene of such a variant acetyl-CoA carboxylase into a plant by genetically engineering technology, or by introducing a resistant-imparting variation into a crop acetyl-CoA carboxylase. Furthermore, a plant resistant to a acetyl-CoA carboxylase inhibitor/herbicide can be generated by inducing a site-specific amino acid substitution variation in a crop (acetyl-CoA carboxylase/herbicide target) gene through introduction, into a plant cell, of a nucleic acid into which a base substitution variation, such as a chimeraplasty technique (Gura T. 1999. Repairing the Genome's Spelling Mistakes. Science 285: 316-318) has been introduced.
Examples of the agricultural and horticultural plant provided with resistance by genetic engineering technology include corn, soybean, cotton, rapeseed, and sugar beet resistant to glyphosate, which are already commercially available under trade names of, for example, RoundupReady <registered trademark> and Agrisure GT <registered trademark>. Similarly, there are corn, soybean, cotton, and rapeseed provided with resistance to glufosinate by genetic engineering technology, which are already commercially available under a trade name of, for example, LibertyLink <registered trademark>. Also, cotton provided with resistance to bromoxynil by genetic engineering technology is already commercially available under a trade name of BXN.
The aforementioned “agricultural and horticultural plant” includes plants that are produced by genetic engineering technology, and can synthesize, for example, selective toxins known in the genus Bacillus.
Examples of insecticidal toxins expressed in such genetically engineered plants include insecticidal proteins derived from Bacillus cereus or Bacillus popilliae; δ-endotoxins derived from Bacillus thuringiensis, such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C; insecticidal proteins, such as VIP1, VIP2, VIP3, or VIP3A; insecticidal proteins derived from nematodes; toxins generated by animals, such as scorpion toxin, spider toxin, bee toxin, or insect-specific neurotoxins; mold fungi toxins; plant lectin; agglutinin; protease inhibitors, such as a trypsin inhibitor, a serine protease inhibitor, patatin, cystatin, and a papain inhibitor; ribosome-inactivating proteins (RIP), such as lysine, corn-RIP, abrin, saporin, and briodin; steroid-metabolizing enzymes, such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glucosyl transferase, and cholesterol oxidase; an ecdysone inhibitor; HMG-COA reductase; ion channel inhibitors, such as sodium channel inhibitor and calcium channel inhibitor; juvenile hormone esterase; diuretic hormone receptor; stilbene synthase; bibenzyl synthase; chitinase; and glucanase.
Examples of toxins expressed in such genetically engineered plants include hybrid toxins of δ-endotoxin proteins, such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C and insecticidal proteins, such as VIP1, VIP2, VIP3, or VIP3A; partially deleted toxins; and modified toxins. Such hybrid toxins are produced from a new combination of the different domains of such proteins by using a genetic engineering technology. A known example of a partially deleted toxin is Cry1Ab wherein a portion of the amino acid sequence is deleted. A modified toxin is produced by substitution of one or more amino acids of a natural toxin.
Examples of such toxins and genetically engineered plants capable of synthesizing the toxins are described in patent documents, such as EP-A-0374753, WO 93/07278, WO 95/34656, EP-A-0427529, EP-A-451878, and WO 03/052073. Toxins contained in such genetically engineered plants provide the plants with resistance particularly to insect pests belonging to Coleoptera, Diptera, and Lepidoptera.
Genetically engineered plants containing one or more insecticidal pest-resistant genes and expressing one or more toxins have already been known, and some of the genetically engineered plants are commercially available. Examples of the genetically engineered plants include YieldGard <registered trademark> (a corn variety expressing Cry1Ab toxin), YieldGard Rootworm <registered trademark> (a corn variety for expressing Cry3Bb1 toxin), YieldGard Plus <registered trademark> (a corn variety expressing Cry1Ab and Cry3Bb1 toxins), Herculex I<registered trademark> (a corn variety expressing phosphinotricine N-acetyl transferase (PAT) for imparting resistance to Cry1Fa2 toxin and glufosinate), NuCOTN33B <registered trademark> (a cotton variety expressing Cry1Ac toxin), Bollgard I<registered trademark> (a cotton variety expressing Cry1Ac toxin), Bollgard II<registered trademark> (a cotton variety expressing Cry1Ac and Cry2Ab toxins), VIPCOT <registered trademark> (a cotton variety expressing VIP toxin), NewLeaf <registered trademark> (a potato variety expressing Cry3A toxin), NatureGard <registered trademark> Agri sure <registered trademark> GT Advantage (GA21 glyphosate-resistant trait), Agrisure <registered trademark> CB Advantage (Bt11 corn borer (CB) trait), and Protecta <registered trademark>.
The aforementioned useful plant also encompasses plants produced by a genetic engineering technology and exhibiting the ability to generate anti-pathogenic substances having selective action.
Examples of such anti-pathogenic substances include PR proteins (PRPs, described in EP-A-0392225); ion channel inhibitors, such as a sodium channel inhibitor and a calcium channel inhibitor (e.g., KP1, KP4, and KP6 toxins produced by viruses are known); stilbene synthase; bibenzyl synthase; chitinase; glucanase; and anti-pathogenic substances generated by microorganisms, such as a peptide antibiotic, an antibiotic having a hetero ring, and a protein factor associated with resistance to plant diseases (which is called a plant disease-resistant gene and is described in WO 03/000906). These anti-pathogenic substances and genetically engineered plants producing the substances are described in, for example, EP-A-0392225, WO 95/33818, and EP-A-0353191.
The aforementioned useful plant also encompasses plants provided with useful properties (e.g., improved oil ingredient and increased amino acid content) by genetically engineering technology. Examples of such plants include VISTIVE <registered trademark> (low linolenic soybean having reduced linolenic content) or high-lysine (high-oil) corn (corn having increased lysine or oil content).
The aforementioned useful plant also encompasses stack varieties including combinations of a plurality of useful properties, such as the aforementioned classic herbicidal properties or herbicide-resistant genes, harmful insect-resistant genes, anti-pathogenic substance-producing genes, and useful properties (e.g., improved oil ingredient, and increased amino acid content).
During formulation or spraying, the compound of the present invention may optionally be applied in the form of a mixture with, for example, another herbicide, any insecticide, a bactericide, a plant growth regulator, or a synergist.
In particular, the application of the compound with another herbicide is expected to cause cost reduction resulting from reduced amount of the applied herbicide, an increase in herbicidal spectrum attributed to synergistic effects of the mixed herbicide, and a higher herbicidal effect. In this case, the compound may be used in combination of a plurality of known herbicides.
Examples of preferred herbicides used in combination with the compound of the present invention include 4-CPA, 4-CPA-salts, 4-CPB, 4-CPP, 2,4-D (2,4-PA), 2,4-D-salts, 2,4-D-esters, 3,4-DA, 2,4-DB, 2,4-DB-salts, 2,4-DB-esters, 3,4-DB, 2,4-DEB, 2,4-DEP, 3,4-DP, 2,4,5-T, 2,4,5-T-salts, 2,4,5-T-esters, 2,4,5-TB, 2,3,6-TBA (TCBA), 2,3,6-TBA-salts, acetochlor, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrolein, alachlor, allidochlor (CDAA), alloxydim, alloxydim-sodium, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidochlor, amidosulfuron, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-salts, amiprophos, amiprophos-methyl, amitrole (aminotriazole, ATA), ammonium sulfamate (AMS), anilofos, anisuron, asulam, asulam-salts, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne (azyprotryn), barban (CBN), BCPC, beflubutamid, beflubutamid-M, benazolin, benazolin-ethyl, benazolin-salts, bencarbazone, benfluralin (benefin), benfuresate, bensulfuron, bensulfuron-methyl, bensulide (SAP), bentazon (bentazone), bentazone-sodium, bentranil, benzadox, benzadox-ammonium, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzoylprop-ethyl, benzthiazuron, bicyclopyrone, bifenox, bilanafos (bialaphos), bilanafos-sodium, binapacryl, bispyribac, bispyribac-sodium, bixlozone, borax, bromacil, bromacil-salts, bromobonil, bromobutide, bromofenoxim, bromopyrazon, bromoxynil, bromoxynil-potassium, bromoxynil-esters, butachlor, butafenacil, butamifos, butenachlor, butralin (butraline), buthidazole, buthiuron, butroxydim, buturon, butylate, cafenstrole, calcium cyanamide, cambendichlor, calcium chlorate, carbasulam, carbetamide, carboxazole, carfentrazone, carfentrazone-ethyl, CDEA, CEPC, chlomethoxyfen (chlomethoxynil), chloramben, chloramben-salts, chloramben-methyl, chloramben-methylammonium, chloranocryl (dicryl), chlorazifop, chlorazifop-propargyl, chlorazine, chlorbromuron, chlorbufam (BIPC), chloreturon, chlorfenac (fenac), chlorfenac-salts, chlorfenprop, chlorfenprop-methyl, chlorflurazole, chlorflurenol, chlorflurenol-methyl, chloridazon (PAC, pyrazon), chlorimuron, chlorimuron-ethyl, chlornidine, chlornitrofen (CNP), chloroacetic acid (monochloroacetic acid), sodium chloroacetate (SMA), chlorotoluron, chloroxuron, chloroxynil, chlorprocarb, chlorphtalim, chlorpropham (IPC), chlorsulfuron, chlorthal (TCTP), chlorthal-esters, chlorthiamid (DCBN), cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clacyfos, clethodim, cliodinate, clodinafop, clodinafop-propargyl, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-salts, cloransulam, cloransulam-methyl, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanamide, cyanazine, cycloate, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cycloxydim, cycluron (COMU), cyhalofop, cyhalofop-butyl, cyperquat, cyperquat-chloride, cyprazine, cyprazole, cypromid, daimuron (dymron), dalapon, dalapon-salts, dazomet, dazomet-sodium, delachlor, desmedipham, desmetryn, di-allate, dicamba (MDBA), dicamba-salts, dicamba-esters, dichlobenil (DBN), dichloraurea (DCU), dichlormate, o-dichlorobenzene, (DCB), dichlorprop, dichlorprop-salts, dichlorprop-esters, dichlorprop-P, dichlorprop-P-salts, dichlorprop-P-esters, diclofop, diclofop-methyl, diclofop-P, diclofop-P-methyl, diclosulam, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat methyl sulfate, diflufenican, diflufenzopyr, diflufenzopyr-sodium, dimefuron, dimepiperate, dimesulfazet, dimethachlor, dimethametryn, dimethenamid, dimethenamid-p, dimexano, dimidazon, dimethyl disulfide, dinitramine, dinofenate, dinoprop, dinosam, dinoseb (DNBP), dinoseb-salts, dinoseb-esters, dinoterb, dinoterb-salts, dinoterb-esters, diphenamid, dipropalin, dipropetryn, diquqt, diquqt dibromide, disul (2,4-PS), disul-sodium, dithiopyr, diuron (DCMU), DMPA, DNOC, DNOC-salts, EBEP, eglinazine, eglinazine-ethyl, endothal, endothal-salts, epronaz, EPTC, epyrifenacil, erbon, esprocarb, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethidimuron, ethiolate, ethiozin, ethofumesate, ethoxyfen, ethoxyfen-ethyl, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop (2,4,5-TP, silvex), fenoprop-salts, fenoprop-esters, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-p, fenoxaprop-p-ethyl, fenoxasulfone, fenquinotrione, fenteracol, fenthiaprop, fenthiaprop-ethyl, fentrazamide, ferrous sulfate, fenuron, fenuron-TCA, flamprop, flamprop-esters, flamprop-M, flamprop-M-esters, flazasulfuron, florasulam, florpyrauxifen, florpyrauxifen-benzyl, fluazifop, fluazifop-esters, fluazifop-P, fluazifop-p-esters, fluazolate, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flufenpyr-ethyl, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoromidine, fluoronitrofen (CFNP), fluothiuron, flupoxam, flupropacil, flupropanate (tetrapion), flupropanate-sodium, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron-sodium, flupyrsulfuron-methyl-sodium, fluridone, flurochloridone, fluroxypyr, fluroxypyr-esters, flurtamone, fluthiacet, fluthiacet-methyl, fomesafen, fomesafen-sodium, foramsulfuron, fosamine, fosamine-ammonium, furyloxyfen, glufosinate, glufosinate-salts, glufosinate-P, glufosinate-P-salts, glyphosate, glyphosate-salts, halauxifen, halauxifen-methyl, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-sodium, haloxyfop-esters, haloxyfop-P, haloxyfop-P-esters, herbimycin, hexachloroacetone (HCA), hexazinone, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-i sopropylammonium, imazaquin, imazaquin-methyl, imazaquin-salts, imazethapyr, imazethapyr-ammonium, imazosulfuron, indanofan, indaziflam, iodobonil, iodosulfuron, iodosulfuron-sodium, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil-salts, ioxynil-esters, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil (isoprocil), isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, ketospiradox-potassium, lactofen, lancotrione, lancotrione-sodium, lenacil, linuron, MCPA, MCPA-salts, MCPA-esters, MCPB, MCPB-salts, MCPB-esters, mecoprop (MCPP), mecoprop-salts, mecoprop-esters, mecoprop-P, mecoprop-P-salts, mecoprop-P-esters, medinoterb, medinoterb acetate, mefenacet, mefluidide, mefluidide-salts, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, metam (carbam), metam-salts, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron (methibenzuron), methalpropalin, methazole, methiobencarb, methiuron, methometon, methoprotryne (methoprotryn), methoxyphenone, methiopyrisulfuron, methiozolin, methyl azide, methyl bromide, methyl dymron, methyl iodide, methyl isothiocyanate, metobenzuron, metobromuron, metolachlor, S-metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, metsulfuron-methyl, molinate, monalide, monisouron, monolinuron, monosulfuron, monosulfuron-methyl, monuron (CMU), monuron-TCA, morfamquat, morfamquat dichloride, naproanilide, napropamide, napropamide-M, naptalam (NPA), naptalam-sodium, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen (NIP, niclofen), nitrofluorfen, norflurazon, noruron (norea), OCH, oleic acid, orbencarb, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxapyrazon-salts, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, paraquat dichloride, paraquat dimethylsulfate, pebulate, pelargonic acid (nonanoic acid), pendimethalin, penoxsulam, pentachlorophenol, sodium pentachlorophenoxide, pentachlorophenyl laurate, pentanochlor (solan, CMMP), pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, picloram, picloram-salts, picloram-esters, picolinafen, pinoxaden, piperophos, potassium azide, potassium cyanate, pretilachlor, primisulfuron, primisulfuron-methyl, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, proglinazine-ethyl, prometon, prometryn (prometryne), propachlor, propanil (DCPA), propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propoxycarbazone-sodium, propyrisulfuron, propyzamide (pronamide), prosulfalin, prosulfocarb, prosulfuron, proxan (IPX), proxan-sodium, prynachlor, pydanon, pyraclonil, pyraflufen, pyraflufen-ethyl, pyrasulfotole, pyrazolynate (pyrazolate), pyrazosulfuron, pyrazosulfuron-ethyl, pyrazoxyfen, pyribambenz-isopropyl, pyribambenz-propyl, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrithiobac, pyrithiobac-sodium, pyroxasulfone, pyroxsulam, quinclorac, quinclorac-dimethylammonium, quinclorac-methyl, quinmerac, quinoclamine (ACN), quinonamid, quizalofop, quizalofop-esters, quizalofop-P, quizalofop-P-esters, rhodethanil, rimsulfuron, saflufenacil, sebuthylazine, secbumeton, sethoxydim, siduron, simazine (CAT), simeton, simetryn (simetryne), sodium azide, sodium chlorate, sulcotrione, sulfallate (CDEC), sulfentrazone, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfuric acid, sulglycapin, swep (MCC), tavron, TCA (trichloroacetic acid), TCA-salts, TCA-ethadyl, tebutam (butam), tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb (terbutol, MPMC), terbuchlor, terbumeton, terbuthylazine, terbutryn, tetflupyrolimet, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thiobencarb (benthiocarb), tiafenacil, tiocarbazil, tioclorim, tolpyralate, topramezone, tralkoxydim, triafamone, triallate (tri-allate), triasulfuron, triaziflam, tribenuron, tribenuron-methyl, tricamba, triclopyr, triclopyr-salts, triclopyr-esters, tridiphane, trietazine, trifloxysulfuron, trifloxysulfuron-sodium, trifludimoxadin, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, trihydroxytriazine (cyanuric acid), trimeturon, tripropindan, tritac, tritosulfuron, vernolate, xylachlor, 6-{(difluoromethyl)thio}-N2,N4-diisopropyl-1,3,5-triazine-2,4-diamine (CAS 103427-73-2), methyl
(R)-2-[{7-(2-chloro-4-(trifluoromethyl)phenoxy)naphthalen-2-yl}oxy]propanoate (CAS 103055-25-0), propan-2-one O-(12H-dibenzo[d,g][1,3]dioxocin-6-carbonyl)oxime (CAS 503819-68-9), [{(2-(N-methylmethylsulfonamido)-2-oxoethyl)amino}methyl]phosphonic acid (CAS 98565-18-5), ethyl
2-[{2-(4-((6-chloroquinoxalin-2-yl)oxy)phenoxy)propanoyl}oxy]-3-methyl-3-butenoate (CAS 1191932-79-2), O-(2,4-dimethyl-6-nitrophenyl) O-methylisopropylphosphoramide thioate (CAS 189517-75-7), methyl
5-[N—{(4,6-dimethylpyrimidin-2-yl)carbamoyl}sulfamoyl]-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate (CAS 104770-29-8),
4-[2-chloro-3-{(3,5-dimethyl-1H-pyrazol-1-yl)methyl}-4-(methylsulfonyl)benzoyl]-1,3-dimethyl-1H-pyrazol-5-yl 1,3-dimethyl-1H-pyrazole-4-carboxylate (CAS 1911613-97-2),
4-[2-chloro-4-(methylsulfonyl)-3-{(2,2,2-trifluoroethoxy)methyl}benzoyl]-1-ethyl-1H-pyrazol-5-yl 1,3-dimethyl-1H-pyrazole-4-carboxylate (CAS 1992017-55-6),
1-{2-chloro-3-(3-cyclopropyl-5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-6-(trifluoro methyl)phenyl}piperidin-2-one (CAS 1855929-45-1),
1,3-dimethyl-4-{2-(methyl sulfonyl)-4-(trifluoromethyl)benzoyl}-1H-pyrazol-5-yl
1,3-dimethyl-1H-pyrazole-4-carboxylate (CAS 1622908-18-2), ethyl
2-[{3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)phenoxy)pyridin-2-yl}oxy]acetate (CAS 353292-31-6),
2-methyl-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-(methylsulfonyl)-4-(trifluoromethyl)benzamide (CAS 1400904-50-8),
2-chloro-N-(1-methyl-1H-tetrazol-5-yl)-3-(methylthio)-4-(trifluoromethyl)benzamide (CAS 1361139-71-0),
2-chloro-N-(1-methyl-1H-tetrazol-5-yl)-3-(methylsulfonyl)-4-(trifluoromethyl)benzamide (CAS 1361139-73-2), F4050 (test name), F9600 (test name), F9960 (test name), OK-701 (test name), and SL-1201 (test name). These ingredients may be used alone or in combination of two or more species. When two or more species are used in combination, the proportions thereof may be arbitrarily determined.
Examples of the safener include benoxacor, BPCMS (CSB), cloquintocet, cloquintocet-mexyl, cumyluron, cyometrinil, cyprosulfamide, daimuron (dymron), dichlormid, dicyclonon (diclonon), dietholate, dimepiperate, disulphoton, fenchlorazole, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, hexim, isoxadifen, isoxadifen-ethyl, MCPA, mecoprop, mefenpyr, mefenpyr-diethyl, mephenate, metcamifen, methoxyphenone, 1,8-naphthalic anhydride (NA), octamethylene-diamine, oxabetrinil, 4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (AD67, MON4660), 4-carboxy-3,4-dihydro-2H-oxo-benzopyran-4-acetic acid (CL304415), 2,2-dichloro-N-[2-oxo-2(propenylamino)ethyl]-N-2-propenylacetamide (DKA-24), 2-(dichloromethyl)-2-methyl-1,3-dioxolane (MG191), 2-propenyl 1-oxa-4-azaspiro[4,5]decane-4-carbodithioate (MG838), (3-dichloroacetyl-5-(2-furyl)-2,2-dimethyloxazolidine) (MON13900), (N-allyl-N-[(1,3-dioxolan-2-yl)methyl]dichloroacetamide (PPG-1292), 3-(dichloroacetyl)-2,2-dimethyl-1,3-oxazolidine (R28725), 3-(dichloroacetyl)-2,2,5-trimethyl-1,3-oxazolidine (R29148), and 1-dichloroacetylazepane (TI-35). These ingredients may be used alone or in combination of two or more species. When two or more species are used in combination, the proportions thereof may be arbitrarily determined.
When the compound of the present invention is applied as a herbicide, the compound is usually mixed with an appropriate solid carrier or liquid carrier. If desired, the mixture may be further mixed with a surfactant, a penetrant, a spreading agent, a thickener, an antifreezing agent, a binder, an anticaking agent, a disintegrant, and a stabilizing agent, and the resultant mixture may be practically used in any herbicidal formulation, such as a water-dispersible powder, an emulsion, a flowable agent, a dry flowable agent, a liquid, a powder, a granule, or a gel. From the viewpoint of power saving and an improvement in safety, the aforementioned herbicidal formulation may be encapsulated in a water-soluble package for supply.
Examples of the solid carrier include natural minerals, such as quartz, kaolinite, pyrophyllite, sericite, talc, bentonite, acid clay, attapulgite, zeolite, and diatomaceous earth; inorganic salts, such as calcium carbonate, ammonium sulfate, sodium sulfate, and potassium chloride; synthetic silicic acid; and synthetic silicates.
Examples of the liquid carrier include alcohols, such as ethylene glycol, propylene glycol, and isopropanol; aromatic hydrocarbons, such as xylene, alkylbenzene, and alkylnaphthalene; ethers, such as butyl cellosolve; ketones, such as cyclohexanone; esters, such as γ-butyrolactone; acid amides, such as N-methyl-2-pyrrolidone and N-octyl-2-pyrrolidone; vegetable oils, such as soybean oil, rapeseed oil, cotton seed oil, and castor oil; and water.
These solid and liquid carriers may be used alone or in combination of two or more species.
Examples of the surfactant include nonionic surfactants, such as polyoxyethylene alkyl ethers, polyoxyethylene alkylaryl ethers, polyoxyethylene styrylphenyl ethers, polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters; anionic surfactants, such as alkyl sulfates, alkylbenzene sulfonates, lignin sulfonates, alkyl sulfosuccinates, naphthalene sulfonate, alkylnaphthalene sulfonates, salts of naphthalene sulfonic acid-formalin condensate, salts of alkylnaphthalene sulfonic acid-formalin condensate, polyoxyethylene alkylaryl ether sulfates and phosphates, polyoxyethylene styrylphenyl ether sulfates and phosphates, polycarboxylates, and polystyrene sulfonates; cationic surfactants, such as alkylamine salts and alkyl quaternary ammonium salts; and amphoteric surfactants, such as amino acid-type surfactants and betaine-type surfactants.
No particular limitation is imposed on the amount of such a surfactant contained in the formulation of the present invention, but the amount of the surfactant is preferably 0.05 to 20 parts by mass relative to 100 parts by mass of the formulation. The aforementioned surfactants may be used alone or in combination of two or more species.
During formulation or spraying, the compound of the present invention may optionally be applied in the form of a mixture with, for example, another herbicide, any insecticide, a bactericide, a plant growth regulator, or a synergist.
In particular, the application of the compound with another herbicide is expected to cause cost reduction resulting from reduced amount of the applied herbicide, an increase in herbicidal spectrum attributed to synergistic effects of the mixed herbicide, and a higher herbicidal effect. In this case, the compound may be used in combination of a plurality of known herbicides.
The amount of application of the compound of the present invention varies depending on, for example, the situation of application, the timing of application, the method of application, or the type of cultivated crop. In general, the appropriate amount of the compound is about 0.005 to 50 kg per hectare (ha) in terms of the amount of an active ingredient.
Next will be described specific agricultural chemical formation examples containing the compound of the present invention as an active ingredient. However, the present invention is not limited to these examples. In the following formulation examples, the term “part(s)” refers to part(s) by mass.
These ingredients are homogeneously mixed and pulverized to prepare a water-dispersible powder.
These ingredients are homogeneously mixed to prepare an emulsion.
These ingredients are homogeneously mixed and then wet-pulverized to prepare a flowable agent.
These ingredients are homogeneously mixed and pulverized, and a small amount of water is added to the pulverized mixture, followed by mixing and kneading with stirring. The resultant product is granulated with an extrusion granulator and then dried to prepare a dry flowable agent.
Compound of the present invention No. 3-089 1 part
Bentonite 55 parts
Talc 44 parts
These ingredients are homogeneously mixed and pulverized, and a small amount of water is added to the pulverized mixture, followed by mixing and kneading with stirring. The resultant product is granulated with an extrusion granulator and then dried to prepare a granule.
The present invention will next be described in more detail with reference to Synthesis Examples and Test Examples of the compound of the present invention. However, the present invention should not be construed as being limited to these Examples.
The medium-pressure preparative liquid chromatography described in Synthesis Examples was performed with a medium-pressure preparative apparatus YFLC-Wprep (flow rate: 18 mL/min, column of silica gel 40 μm) available from Yamazen Corporation.
The chemical shift values of proton nuclear magnetic resonance spectroscopy (hereinafter referred to as “1H-NMR”) described bellow were measured at 300 MHz (model: JNM-ECX300 or JNM-ECP300, available from JEOL Ltd.) in deuterated chloroform solvent by use of Me4Si (tetramethylsilane) as a reference substance. In the case of measurement in deuterated dimethyl sulfoxide solvent, “(DMSO-d6)” is described in chemical shift value data. The symbols of the chemical shift values of 1H-NMR have the following meanings:
s: singlet, d: doublet, dd: double doublet, dt: doublet triplet, td: triplet doublet, ddd: double double doublet, t: triplet, q: quartet, sep: septet, m: multiplet, and brs: broad singlet. For the signals that can be analyzed when two or more stereoisomers are present, the chemical shift values of each of the signals are marked with “and.”
Firstly, 322 mg of p-cyanophenylboronic acid, 349 mg of potassium phosphate, 51 mg of 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl, and 12 mg of palladium acetate were added to a mixture of 200 mg of 4-(2-bromobenzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 3 mL of toluene at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred at 110° C. for three hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with chloroform (10 mL×2). The resultant filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography with a gradient of [ethyl acetate:n-hexane=5:95 to 20:80 (by volume, the same shall apply hereinafter)], to thereby yield 90 mg of the target product as a yellow solid.
Melting point: 219-221° C.
1H NMR: δ 7.85-7.95 (m, 1H), 7.55-7.70 (m, 4H), 7.35-7.50 (m, 3H), 3.77 (s, 3H), 3.33 (s, 3H), 2.24 (s, 3H).
Firstly, 2 mL of morpholine was added to 90 mg of 5-methoxy-2,6-dimethyl-4-(2-(4-cyanophenyl)benzo[b]thiophen-3-yl)pyridazin-3 (2H)-one at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred at 95° C. for five hours. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. The resultant residue was dissolved in 10 mL of chloroform, and 1 mol/L hydrochloric acid was added to the solution under ice cooling so as to achieve a pH of 1, followed by stirring of the resultant mixture at room temperature for one hour. After completion of the stirring, the organic phase was separated from the mixture. The resultant organic phase was washed with 5 mL of 1 mol/L hydrochloric acid, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. Thereafter, the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=20:80 to 75:25), to thereby yield 83 mg of the target product as a white solid.
Melting point: 240-242° C.
1H NMR: δ 7.75-7.85 (m, 1H), 7.25-7.50 (m, 7H), 3.47 (s, 3H), 2.17 (s, 3H).
Firstly, 68 mg of 4-chloropyrazole, 206 mg of potassium carbonate, 11 mg of copper iodide, and 21 mg of (1S,2S)-(+)—N,N′-dimethylcyclohexane-1,2-diamine were added to a mixture of 200 mg of 4-(2-bromobenzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 5 mL of N,N-dimethylacetamide at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred at 130° C. for eight hours. After completion of the stirring, 20 mL of ethyl acetate and 20 mL of 28% by mass aqueous ammonia were added to the reaction mixture, and the precipitated insoluble matter was filtered with celite. Subsequently, 35% by mass hydrochloric acid was added to the resultant filtrate under ice cooling so as to achieve a pH of 1, and the resultant mixture was subjected to extraction with 20 mL of ethyl acetate. A solution of 58 mg of lithium hydroxide in 20 mL of water was added to the resultant organic phase at room temperature, to thereby separate the aqueous phase from the mixture. Thereafter, 35% by mass hydrochloric acid was added to the resultant aqueous phase under ice cooling so as to achieve a pH of 1, and then the precipitated solid was filtered. The resultant solid was dissolved in 2 mL of dichloromethane, and 61 mg of triethylamine and 70 mg of n-butyryl chloride were added to the solution under ice cooling. After completion of the addition, the resultant reaction mixture was stirred at room temperature for one hour. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure, and the resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=2:98 to 30:70), to thereby yield 57 mg of the target product as a yellow oily product.
1H NMR: δ 7.75-7.85 (m, 1H), 7.72 (s, 1H), 7.63 (s, 1H), 7.30-7.40 (m, 3H), 3.83 (s, 3H), 2.30 (s, 3H), 2.10-2.20 (m, 2H), 1.20-1.35 (m, 2H), 0.58 (t, J=7.5 Hz, 3H).
Firstly, a solution of 10 mg of lithium hydroxide in 2 mL of water was added to a mixture of 36 mg of 1,3-dimethyl-6-oxo-5-(2-(4-chloro-1H-pyrazol-1-yl)benzo[b]thiophen-3-yl)-1,6-dihydropyridazin-4-yl=(n-butyrate) and 1 mL of tetrahydrofuran at room temperature. After completion of the addition, the reaction mixture was stirred at room temperature for one hour. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. Subsequently, 35% by mass hydrochloric acid was added to the resultant residue so as to achieve a pH of 1, and the precipitated solid was filtered, to thereby yield 30 mg of the target product as a white solid.
1H NMR (DMSO-d6): δ 8.30 (s, 1H), 8.09 (s, 1H), 7.95-8.05 (m, 1H), 7.90 (s, 1H), 7.30-7.45 (m, 2H), 7.20-7.30 (m, 1H), 3.58 (s, 3H), 2.26 (s, 3H).
Firstly, 27.0 g of 2-bromoanisole, 649 mg of palladium acetate, 1.5 g of triphenylphosphine, and 12.0 g of potassium carbonate were added to a mixture of 12.9 g of 2-(6-methoxybenzo[b]thiophen-3-yl)acetic acid and 115 mL of N,N-dimethylformamide at room temperature. After completion of the addition, air in the reaction container was replaced with nitrogen gas, and the reaction mixture was stirred at 100° C. for 11 hours. After completion of the stirring, the reaction mixture was cooled to room temperature, and 24.0 g of potassium carbonate and 49.2 g of methyl iodide were added to the reaction mixture, followed by stirring at room temperature for 13 hours. After completion of the stirring, 200 mL of toluene was added to the reaction mixture, and insoluble matter was filtered with celite. The residue was washed with 20 mL of toluene, and the resultant filtrate was washed with 100 mL of water. Thereafter, the resultant filtrate was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=1:99 to 20:80), to thereby yield 7.93 g of the target product as a colorless oily product.
1H NMR: δ 7.61 (d, J=8.9 Hz, 1H), 7.35-7.45 (m, 2H), 7.32 (d, J=2.4 Hz, 1H), 6.95-7.10 (m, 3H), 3.89 (s, 3H), 3.79 (s, 3H), 3.69 (s, 2H), 3.67 (s, 3H).
Firstly, a solution of 3.4 g of sodium hydroxide in 100 mL of water was added to a mixture of 9.0 g of methyl 2-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)acetate and 60 mL of tetrahydrofuran at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for 12 hours. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. Subsequently, 20 mL of water and 50 mL of hexane were added to the resultant residue, and the aqueous phase was separated from the reaction mixture. Thereafter, 35% by mass hydrochloric acid was added to the resultant aqueous phase under ice cooling so as to achieve a pH of 1, and the precipitated solid was recovered through filtration. The resultant solid was washed sequentially with 20 mL of water and 20 mL of hexane, to thereby yield 7.0 g of the target product as a white solid.
Melting point: 232-234° C.
1H NMR: δ 7.65-7.80 (m, 2H), 7.43 (d, J=2.4 Hz, 1H), 7.30-7.45 (m, 1H), 7.10 (d, J=8.4 Hz, 1H), 6.95-7.05 (m, 1H), 6.94 (dd, J=8.4, 2.4 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H), 3.34 (s, 2H).
Firstly, 4.5 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 4.3 g of pentafluorophenol were added to a mixture of 7.0 g of 2-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)acetic acid and 22 mL of dichloromethane at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for five hours. Subsequently, 8.3 g of diisopropylethylamine was added at room temperature to a mixture of 6.2 g of methylhydrazine sulfate and 30 mL of dichloromethane prepared in another reaction container. After completion of the addition, the resultant mixture was stirred at room temperature for five hours. After completion of the stirring, the previously prepared mixture of 2-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)acetic acid and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added to this reaction mixture at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for three hours. After completion of the stirring, 40 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with 30 mL of dichloromethane. The resultant organic phase was washed with water (30 mL×2), and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. Thereafter, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in 62 mL of ethanol, and 5.0 g of ethyl pyruvate was added to the solution at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for 12 hours. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=1:99 to 15:85), to thereby yield 7.5 g of the target product as a brown oily product.
1H NMR: δ 7.55-7.70 (m, 1H), 7.25-7.45 (m, 3H), 6.90-7.05 (m, 3H), 4.24 (q, J=6.9 Hz, 2H), 4.06 (s, 2H), 3.88 (s, 3H), 3.79 (s, 3H), 3.32 (s, 3H), 2.19 (s, 3H), 1.28 (t, J=6.9 Hz, 3H).
Firstly, 2.1 g of 1,8-diazabicyclo[5,4,0]-7-undecene was added to a mixture of 3.1 g of ethyl 2-(2-(2-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)acetyl)-2-methylhydrazinylidene)propionate and 70 mL of acetonitrile at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the mixture was stirred at 80° C. for five hours. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. The resultant residue was dissolved in 120 mL of ethyl acetate, and 10 mL of 1 mol/L hydrochloric acid was added to the solution at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for one hour. After completion of the stirring, the organic phase was separated from the mixture. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Subsequently, 20 mL of diisopropyl ether was added to the resultant residue, and the precipitated solid was recovered through filtration. The resultant solid was washed with 5 mL of a mixture of diisopropyl ether and acetonitrile (20:1), to thereby yield 952 mg of the target product as a white solid.
Melting point: 243-244° C.
1H NMR: δ 7.25-7.40 (m, 4H), 6.90-7.05 (m, 3H), 6.32 (s, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.75 (s, 3H), 2.18 (s, 3H).
Firstly, 30 mg of triethylamine was added to a mixture of 100 mg of 5-hydroxy-4-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-2,6-dimethylpyridazin-3(2H)-one and 2 mL of dichloromethane under ice cooling. After completion of the addition, the resultant mixture was stirred at room temperature for 30 minutes. After completion of the stirring, 29 mg of n-butyryl chloride was added to the mixture at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for one hour. After completion of the stirring, 5 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with 5 mL of ethyl acetate. The resultant organic phase was washed with 2 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=1:99 to 25:75), to thereby yield 116 mg of the target product as a yellow oily product.
1H NMR: δ 7.25-7.35 (m, 4H), 6.85-7.00 (m, 3H), 3.86 (s, 3H), 3.83 (s, 3H), 3.72 (s, 3H), 2.12 (t, J=7.5 Hz, 2H), 2.10 (s, 3H), 1.25-1.45 (m, 2H), 0.68 (t, J=7.3 Hz, 3H).
Firstly, 1.0 g of 2-(5-fluorobenzo[b]thiophen-3-yl)acetic acid, 250 mg of triphenylphosphine, 987 mg of potassium carbonate, and 107 mg of palladium acetate were added to a mixture of 1.3 g of 1-bromo-4-(difluoromethoxy)benzene and 5 mL of N,N-dimethylformamide at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred at 100° C. for five hours. After completion of the stirring, 789 mg of potassium carbonate and 1.0 g of methyl iodide were added to the reaction mixture under ice cooling, and the resultant mixture was stirred at room temperature for one hour. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with 150 mL of toluene. The resultant filtrate was washed with water (15 mL×2), and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of chloroform:n-hexane=1:99 to 15:85), to thereby yield 1.0 g of the target product as a white solid.
Melting point: 111-113° C.
1H NMR: δ 7.74 (dd, J=8.7, 4.8 Hz, 1H), 7.55-7.65 (m, 2H), 7.43 (dd, J=9.6, 2.4 Hz, 1H), 7.25-7.15 (m, 2H), 7.05 (ddd, J=8.7, 8.7, 2.4 Hz, 1H), 6.57 (t, J=73.8 Hz, 1H), 3.78 (s, 2H), 3.74 (s, 3H).
Firstly, 30 mL of 10% by mass aqueous lithium hydroxide solution was added to a mixture of 2.1 g of methyl 2-(2-(4-(difluoromethoxy)phenyl)-5-fluorobenzo[b]thiophen-3-yl)acetate, 15 mL of tetrahydrofuran, and 15 mL of ethanol at room temperature. After completion of the addition, the reaction mixture was stirred at room temperature for three hours. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. Subsequently, 35% by mass hydrochloric acid was added to the resultant residue under ice cooling so as to achieve a pH of 1, and the precipitated solid was recovered through filtration. The resultant solid was washed with water (15 mL×2), to thereby yield 1.8 g of the target product as a white solid.
Melting point: 203-204° C.
1H NMR: δ 7.75 (dd, J=9.0, 4.8 Hz, 1H), 7.55-7.65 (m, 2H), 7.45 (dd, J=9.6, 2.4 Hz, 1H), 7.20-7.30 (m, 2H), 7.12 (ddd, J=9.0, 9.0, 2.4 Hz, 1H), 6.57 (t, J=73.8 Hz, 1H), 3.82 (s, 2H).
Firstly, 1.1 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1.0 g of pentafluorophenol were added to a mixture of 1.8 g of 2-(2-(4-(difluoromethoxy)phenyl)-5-fluorobenzo[b]thiophen-3-yl)acetic acid and 9 mL of dichloromethane at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for two hours. Subsequently, 2.2 g of triethylamine was added dropwise under ice cooling to a mixture of 1-6 g of methylhydrazine sulfate and 5 mL of dichloromethane prepared in another reaction container. After completion of the dropwise addition, the resultant mixture was stirred at room temperature for three hours. After completion of the stirring, the previously prepared mixture of 2-(2-(4-(difluoromethoxy)phenyl)-5-fluorobenzo[b]thiophen-3-yl)acetic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and pentafluorophenol was added dropwise to the reaction mixture under ice cooling. After completion of the dropwise addition, the resultant mixture was stirred at room temperature for 14 hours. After completion of the stirring, 15 mL of water was added to the reaction mixture, and the organic phase was separated. The resultant organic phase was washed with 15 mL of aqueous saturated sodium hydrogen carbonate solution, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was dissolved in 8 mL of ethanol, and 1.2 g of ethyl pyruvate was added to the solution at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred at 80° C. for four hours. After completion of the stirring, the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=3:97 to 25:75), to thereby yield 1.5 g of the target product as a pale yellow solid.
Melting point: 100-101° C.
1H NMR: δ 7.73 (dd, J=8.7, 4.8 Hz, 1H), 7.55-7.65 (m, 2H), 7.35-7.50 (m, 1H), 7.15-7.25 (m, 2H), 7.12 (ddd, J=8.7, 8.7, 2.4 Hz, 1H), 6.56 (t, J=73.8 Hz, 1H), 4.29 (q, J=7.5 Hz, 2H), 4.16 (s, 2H), 3.40 (s, 3H), 2.10 (s, 3H), 1.31 (t, J=7.5 Hz, 3H).
Firstly, 904 mg of 1,8-diazabicyclo[5,4,0]-7-undecene was added to a mixture of 1.4 g of ethyl 2-(2-(2-(2-(4-(difluoromethoxy)phenyl)-5-fluorobenzo[b]thiophen-3-yl)acetyl)-2-methylhydrazinylidene)propionate and 30 mL of acetonitrile at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the resultant mixture was heated to 90° C. and stirred for one hour. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. The resultant residue was dissolved in 14 mL of ethyl acetate, and 1 mol/L hydrochloric acid was added to the solution so as to achieve a pH of 1 under ice cooling. The resultant mixture was stirred at room temperature for one hour. After completion of the stirring, the organic phase was separated from the mixture. The resultant organic phase was washed with 5 mL of 1 mol/L hydrochloric acid, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Subsequently, 10 mL of diisopropyl ether and 0.5 mL of acetonitrile were added to the resultant residue, and the precipitated solid was recovered through filtration, to thereby yield 469 mg of the target product as a white solid.
Melting point: 164-165° C.
1H NMR (DMSO-d6): δ 10.54 (brs, 1H), 8.06 (dd, J=8.7, 4.8 Hz, 1H), 7.40-7.50 (m, 2H), 7.27 (t, J=74.1 Hz, 1H), 7.20-7.25 (m, 1H), 7.15-7.20 (m, 2H), 7.10 (dd, J=9.9, 2.4 Hz, 1H), 3.57 (s, 3H), 2.19 (s, 3H).
Firstly, 30% by mass hydrogen bromide-acetic acid solution was added dropwise under ice cooling to a mixture of 10.5 g of 2-(4-chlorophenyl)-5-fluorobenzo[b]thiophene, 3.2 g of paraformaldehyde, and 60 mL of chloroform, and the resultant mixture was stirred at 40° C. for three hours. After completion of the stirring, 200 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with 40 mL of chloroform. The resultant organic phase was washed with 100 mL of water and 100 mL of aqueous saturated sodium hydrogen carbonate solution, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Subsequently, 50 mL of n-hexane was added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 12.4 g of the target product as a gray solid.
Melting point: 124-126° C.
1H NMR: δ 7.76 (dd, J=8.7, 4.8 Hz, 1H), 7.45-7.65 (m, 5H), 7.10-7.20 (m, 1H), 4.66 (s, 2H).
Firstly, 1.7 g of potassium carbonate and 1.2 g of trimethylsilyl cyanide were added to a mixture of 3.6 g of 3-bromomethyl-2-(4-chlorophenyl)-5-fluorobenzo[b]thiophene and 15 mL of acetonitrile at room temperature, and the resultant mixture was stirred at 80° C. for 12 hours. After completion of the stirring, 20 mL of 10% by mass aqueous sodium hydroxide solution was added to the reaction mixture under ice cooling, and the resultant mixture was subjected to extraction with 40 mL of dichloromethane. The resultant organic phase was washed with 10 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Subsequently, 50 mL of n-hexane and 5 mL of diisopropyl ether were added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 2.8 g of the target product as a pale yellow solid.
Melting point: 161-163° C.
1H NMR: δ 7.81 (dd, J=8.1, 4.8 Hz, 1H), 7.40-7.55 (m, 5H), 7.15-7.25 (m, 1H), 3.81 (s, 2H).
Firstly, 10 mL of concentrated sulfuric acid was added to a mixture of 10.0 g of 2-(2-(4-chlorophenyl)-5-fluorobenzo[b]thiophen-3-yl)acetonitrile, 60 mL of acetic acid, and 20 mL of water under ice cooling. After completion of the addition, the reaction mixture was stirred under reflux with heating for 12 hours. After completion of the stirring, the reaction mixture was added dropwise to 200 mL of water under ice cooling, and the precipitated solid was recovered through filtration. To the resultant solid were added 150 mL of 5% by mass aqueous potassium hydroxide solution and 150 mL of dichloromethane at room temperature, and the organic phase was separated through a phase separation process. The resultant organic phase was subjected to extraction with 150 mL of 5% by mass aqueous potassium hydroxide solution. The resultant aqueous phases were combined and then washed with 50 mL of dichloromethane. Subsequently, 20 mL of 35% by mass hydrochloric acid was added to the resultant aqueous phase under ice cooling, and the resultant mixture was subjected to extraction with 200 mL of ethyl acetate. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Subsequently, 300 mL of n-hexane and 30 mL of diisopropyl ether were added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 7.7 g of the target product as a white solid.
Melting point: 202-204° C.
1H NMR: δ 7.76 (dd, J=9.0, 4.8 Hz, 1H), 7.50-7.60 (m, 2H), 7.40-7.50 (m, 3H), 7.10-7.20 (m, 1H), 3.82 (s, 2H).
Firstly, 10.2 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 9.8 g of pentafluorophenol were added to a mixture of 17.1 g of 2-(2-(4-chlorophenyl)-5-fluorobenzo[b]thiophen-3-yl)acetic acid and 150 mL of dichloromethane at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for 18 hours. In another reaction container, 21.6 g of triethylamine was added dropwise to a mixture of 15.4 g of methylhydrazine sulfate and 90 mL of dichloromethane under ice cooling. After completion of the dropwise addition, the resultant mixture was stirred under ice cooling for one hour. After completion of the stirring, the previously prepared mixture of 2-(2-(4-chlorophenyl)-5-fluorobenzo[b]thiophen-3-yl)acetic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and pentafluorophenol was added dropwise to the reaction mixture under ice cooling. After completion of the dropwise addition, the resultant mixture was stirred at room temperature for 18 hours. After completion of the stirring, 200 mL of water was added to the reaction mixture at room temperature, and the resultant mixture was subjected to extraction with 150 mL of dichloromethane. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was dissolved in 100 mL of ethanol, and 12.4 g of ethyl pyruvate was added to the solution. After completion of the addition, the resultant mixture was stirred at 70° C. for two hours. After completion of the stirring, the solvent was distilled off under reduced pressure. Subsequently, 100 mL of water was added to the resultant residue, and the resultant mixture was subjected to extraction with 150 mL of diethyl ether. The resultant organic phase was washed with 5% by mass aqueous potassium carbonate solution (100 mL×2), and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, to thereby yield 11.1 g of the target product as a white solid.
Melting point: 125-127° C.
1H NMR: δ 7.74 (dd, J=8.9, 4.8 Hz, 1H), 7.56 (d, J=8.5 Hz, 2H), 7.37-7.48 (m, 3H), 7.05-7.14 (m, 1H), 4.30 (q, J=7.2 Hz, 2H), 4.16 (s, 2H), 3.41 (s, 3H), 2.29 (s, 3H), 1.31 (t, J=7.2 Hz, 3H).
Firstly, 11.3 g of 1,8-diazabicyclo[5.4.0]-7-undecene was added to a mixture of 11.1 g of ethyl 2-(2-(2-(2-(4-chlorophenyl)-5-fluorobenzo[b]thiophen-3-yl)acetyl)-2-methylhydrazinylidene)propionate and 50 mL of acetonitrile at room temperature. After completion of the addition, the reaction mixture was stirred at 80° C. for six hours. After completion of the stirring, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in 500 mL of ethyl acetate, and 100 mL of 1 mol/L hydrochloric acid and 200 mL of water were added to the solution under ice cooling. Thereafter, the organic phase was separated through a phase separation process. The resultant aqueous phase was subjected to extraction with ethyl acetate (300 mL×2). The resultant organic phases were combined, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Subsequently, 50 mL of diisopropyl ether and 5 mL of acetonitrile were added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 9.9 g of the target product as a white solid.
Melting point: 258-259° C.
1H NMR: δ 7.75 (dd, J=8.9, 4.8 Hz, 1H), 7.24-7.26 (m, 4H), 7.07-7.16 (m, 1H), 6.94-7.01 (m, 1H), 6.31 (brs, 1H), 3.63 (s, 3H), 2.19 (s, 3H).
1H NMR (DMSO-d6): δ 10.57 (brs, 1H), 8.08 (dd, J=8.9, 4.8 Hz, 1H), 7.40-7.50 (m, 4H), 7.25-7.35 (m, 1H), 7.11 (dd, J=9.9, 2.4 Hz, 1H), 3.57 (s, 3H), 2.19 (s, 3H).
Firstly, 24.5 g of N-bromosuccinimide was added to a mixture of 33.4 g of ethyl 2-(5-chlorobenzo[b]thiophen-3-yl)acetate, 140 mL of N,N-dimethylformamide, and 14 mL of acetic acid at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the resultant mixture was heated to 60° C. and stirred at 60° C. for four hours. After completion of the stirring, 14.0 g of N-bromosuccinimide was added to the mixture at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the resultant mixture was heated to 60° C. and stirred at 60° C. for one hour. After completion of the stirring, the reaction mixture was added dropwise to 140 mL of water under ice cooling. After completion of the dropwise addition, the reaction mixture was subjected to extraction with 150 mL of diethyl ether. The resultant organic phase was washed sequentially with 50 mL of water, 20 mL of aqueous saturated ammonium chloride solution, and 20 mL of 5% by mass aqueous sodium hydrogen sulfite solution. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Subsequently, 100 mL of hexane was added to the resultant residue, and the resultant mixture was stirred at room temperature for 12 hours. Thereafter, the precipitated solid was recovered through filtration, and the resultant solid was washed with 20 mL of hexane, to thereby yield 26.3 g of the target product as a pale yellow solid.
Melting point: 70-71° C.
1H NMR: δ 7.60-7.70 (m, 2H), 7.31 (dd, J=8.7, 1.9 Hz, 1H), 4.18 (q, J=7.2 Hz, 2H), 3.84 (s, 2H), 1.26 (t, J=7.2 Hz, 3H).
Firstly, 3.8 g of 4-fluoro-2-methoxyphenylboronic acid, 8.3 g of potassium carbonate, and 1.7 g of tetrakis(triphenylphosphine)palladium were added to a mixture of 5.0 g of ethyl 2-(2-bromo-5-chlorobenzo[b]thiophen-3-yl)acetate, 50 mL of 1,4-dioxane, and 10 mL of water at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 90° C. for three hours. After completion of the stirring, 50 mL of water and 100 mL of ethyl acetate were added to the reaction mixture at room temperature. After completion of the addition, insoluble matter was filtered with celite. The organic phase was separated from the resultant filtrate. The resultant organic phase was washed with 50 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=2:98 to 10:90), to thereby yield 3.7 g of the target product as a pale yellow solid.
Melting point: 103-105° C.
1H NMR: δ 7.65-7.75 (m, 2H), 7.25-7.45 (m, 2H), 6.70-6.80 (m, 2H), 4.14 (q, J=7.2 Hz, 2H), 3.77 (s, 3H), 3.64 (s, 2H), 1.23 (t, J=7.2 Hz, 3H).
Firstly, a mixture of 6.8 g of sodium hydroxide and 190 mL of water was added dropwise to a mixture of 21.6 g of ethyl 2-(5-chloro-2-(4-fluoro-2-methoxyphenyl)benzo[b]thiophen-3-yl)acetate, 266 mL of tetrahydrofuran, and 150 mL of water under ice cooling. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 13 hours. After completion of the stirring, the organic solvent was distilled off under reduced pressure. Subsequently, 35% by mass hydrochloric acid was added to the resultant residue under ice cooling so as to achieve a pH of 1, and the precipitated solid was recovered through filtration. The resultant solid was washed sequentially with water (20 mL×2) and 20 mL of hexane, to thereby yield 19.9 g of the target product as a white solid.
Melting point: 186-188° C.
1H NMR: δ 7.65-7.75 (m, 2H), 7.25-7.40 (m, 2H), 6.70-6.80 (m, 2H), 3.77 (s, 3H), 3.68 (s, 2H).
Firstly, 12.0 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 11.5 g of pentafluorophenol were added to a mixture of 20.0 g of 2-(5-chloro-2-(4-fluoro-2-methoxyphenyl)benzo[b]thiophen-3-yl)acetic acid and 300 mL of dichloromethane at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for 13 hours. In another reaction container, 29.5 g of diisopropylethylamine was added dropwise to a mixture of 24.6 g of methylhydrazine sulfate and 300 mL of dichloromethane at room temperature. After completion of the dropwise addition, the resultant mixture was stirred at room temperature for 13 hours. After completion of the stirring, the previously prepared mixture of 2-(5-chloro-2-(4-fluoro-2-methoxyphenyl)benzo[b]thiophen-3-yl)acetic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and pentafluorophenol was added dropwise to the reaction mixture under ice cooling. After completion of the dropwise addition, the resultant mixture was stirred at room temperature for three hours. After completion of the stirring, 500 mL of water was added to the reaction mixture, and the organic phase was separated through a phase separation process. The resultant organic phase was washed with 500 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was dissolved in 180 mL of ethanol, and 13.2 g of ethyl pyruvate was added to the solution at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 45° C. for 10 hours. After completion of the stirring, the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=2:98 to 20:80). Subsequently, 50 mL of diisopropyl ether was added to the resultant crude product, and the precipitated solid was recovered through filtration. The resultant solid was washed with 10 mL of diisopropyl ether, to thereby yield 15.9 g of the target product as a white solid.
Melting point: 126-128° C.
1H NMR: δ 7.65-7.75 (m, 2H), 7.35-7.45 (m, 1H), 7.25-7.35 (m, 1H), 6.65-6.80 (m, 2H), 4.26 (q, J=7.2 Hz, 2H), 4.03 (s, 2H), 3.77 (s, 3H), 3.34 (s, 3H), 2.24 (s, 3H), 1.30 (t, J=7.2 Hz, 3H).
Firstly, 8.6 g of 1,8-diazabicyclo[5,4,0]-7-undecene was added to a mixture of 13.4 g of ethyl 2-(2-(2-(5-chloro-2-(4-fluoro-2-methoxyphenyl)benzo[b]thiophen-3-yl)acetyl)-2-methylhydrazinylidene)propionate and 57 mL of acetonitrile at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the resultant mixture was heated to 90° C. and stirred at 90° C. for five hours. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. Subsequently, 50 mL of water and 350 mL of ethyl acetate were added to the resultant residue, and 35% by mass hydrochloric acid was added to the mixture under ice cooling so as to achieve a pH of 1. The organic phase was separated from the resultant mixture. The resultant organic phase was washed sequentially with 1 mol/L hydrochloric acid (50 mL×2) and 100 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Subsequently, 100 mL of diisopropyl ether and 2 mL of acetonitrile were added to the resultant residue. After completion of the addition, the precipitated solid was recovered through filtration, to thereby yield 11.3 g of the target product as a white solid.
Melting point: 221-223° C.
1H NMR: δ 7.70-7.80 (m, 1H), 7.20-7.40 (m, 3H), 6.60-6.75 (m, 2H), 6.02 (s, 1H), 3.79 (s, 3H), 3.73 (s, 3H), 2.21 (s, 3H).
Firstly, 3.7 g of 2-methoxyphenylboronic acid, 10.6 g of potassium phosphate, and 1.2 g of tetrakis(triphenylphosphine)palladium were added to a mixture of 8.0 g of 4-(2-bromo-5-chlorobenzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 60 mL of toluene at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 110° C. for four hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with 100 mL of ethyl acetate. The resultant filtrate was washed with 100 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=20:80 to 40:60), to thereby yield 7.0 g of the target product as an ocher solid.
Melting point: 174-175° C.
1H NMR: δ 7.72 (d, J=8.7 Hz 1H), 7.43 (dd, J=2.1, 0.6 Hz, 1H), 7.28-7.36 (m, 3H), 6.86-6.96 (m, 2H), 3.74 (s, 3H), 3.70 (s, 3H), 3.36 (s, 3H), 2.11 (s, 3H).
Firstly, 1.5 g of tert-butyl carbamate, 127 mg of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl, 3.0 g of cesium carbonate, and 42 mg of palladium acetate were added to a mixture of 1.2 g of 4-(5-chloro-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 15 mL of 1,4-dioxane at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 110° C. for six hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with 30 mL of ethyl acetate. The resultant filtrate was washed with 20 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, to thereby yield 1.4 g of the target product as a pale yellow oily product. This product was used in the next step without further purification.
1H NMR: δ 7.72 (d, J=9.0 Hz, 1H), 7.40-7.50 (m, 1H), 7.28-7.38 (m, 3H), 6.88-6.95 (m, 1H), 6.87 (d, J=9.0 Hz, 1H), 6.60 (brs, 1H), 3.74 (s, 3H), 3.69 (s, 3H), 3.36 (s, 3H), 2.08 (s, 3H), 1.50 (s, 9H).
Firstly, 5 mL of trifluoroacetic acid was added to a mixture of 1.4 g of tert-butyl (3-(5-methoxy-2,6-dimethyl-3-oxo-2,3-dihydropyridazin-4-yl)-2-(2-methoxyphenyl)benzo[b]thiophen-5-yl)carbamate and 10 mL of dichloromethane under ice cooling. After completion of the addition, the resultant mixture was stirred at room temperature for 20 hours. After completion of the stirring, the solvent was distilled off under reduced pressure. Subsequently, 80 mL of ethyl acetate was added to the resultant residue, and the mixture was washed with 30 mL of aqueous saturated sodium hydrogen carbonate solution and 20 mL of water. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Subsequently, 20 mL of diisopropyl ether was added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 390 mg of the target product as a pale yellow solid.
Melting point: 219-221° C.
1H NMR: δ 7.57 (d, J=9.3 Hz, 1H), 7.35 (dd, J=7.5, 1.5 Hz, 1H), 7.20-7.28 (m, 2H), 6.75-6.95 (m, 3H), 3.74 (s, 3H), 3.68 (s, 3H), 3.37 (s, 3H), 2.09 (s, 3H), 1.61 (brs, 2H).
Firstly, 4.4 g of 35% by mass hydrochloric acid was added to a mixed suspension of 1.7 g of 4-(5-amino-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 15 mL of water under ice cooling. After completion of the addition, a mixture of 345 mg of sodium nitrite and 2.5 mL of water was added dropwise to the mixed suspension under ice cooling, and the resultant mixture was stirred under ice cooling for 30 minutes. After completion of the stirring, a mixture of 1.9 g of sodium iodide and 5.5 mL of water was added dropwise to the resultant mixture under ice cooling. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 20 hours. After completion of the stirring, 30 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with 50 mL of ethyl acetate. The resultant organic phase was washed with 5% by mass aqueous sodium thiosulfate solution (30 mL×2), and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=20:80 to 40:60), to thereby yield 1.5 g of the target product as an orange solid.
Melting point: 161-163° C.
1H NMR: δ 7.76-7.78 (m, 1H), 7.53-7.62 (m, 2H), 7.26-7.36 (m, 2H), 6.92 (dd, J=7.5, 1.2 Hz, 1H), 6.87 (d, J=7.5 Hz, 1H), 3.74 (s, 3H), 3.70 (s, 3H), 3.35 (s, 3H), 2.11 (s, 3H).
Firstly, 62 mg of cyclopropylboronic acid, 256 mg of potassium phosphate, and 28 mg of tetrakis(triphenylphosphine)palladium were added to a mixture of 250 mg of 4-(5-iodo-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 3 mL of toluene at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 110° C. for two hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with 10 mL of ethyl acetate. The resultant filtrate was washed with water (5 mL×2), and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=20:80 to 40:60), to thereby yield 157 mg of the target product as an orange oily product.
1H NMR: δ 7.69 (d, J=7.8 Hz, 1H), 7.26-7.36 (m, 2H), 7.20 (d, J=1.8 Hz, 1H), 6.85-7.00 (m, 3H), 3.74 (s, 3H), 3.68 (s, 3H), 3.37 (s, 3H), 2.12 (s, 3H), 1.95-2.05 (m, 1H), 0.92-1.00 (m, 2H), 0.62-0.70 (m, 2H).
Firstly, a mixture of 140 mg of 4-(5-cyclopropyl-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 1.5 mL of morpholine was stirred at 100° C. for eight hours. After completion of the stirring, 5 mL of water was added to the reaction mixture, and 35% by mass hydrochloric acid was added to the mixture under ice cooling so as to achieve a pH of 1. After completion of the addition, the resultant mixture was subjected to extraction with 15 mL of ethyl acetate. The resultant organic phase was washed with 5 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Subsequently, 5 mL of diisopropyl ether was added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 42 mg of the target product as a white solid.
Melting point: 182-184° C.
1H NMR: δ 7.72 (d, J=8.4 Hz, 1H), 7.30-7.40 (m, 2H), 7.15-7.18 (m, 1H), 7.02-7.08 (m, 1H), 6.90-7.00 (m, 2H), 6.39 (brs, 1H), 3.78 (s, 3H), 3.74 (s, 3H), 2.17 (s, 3H), 1.92-2.04 (m, 1H), 0.90-1.00 (m, 2H), 0.65-0.75 (m, 2H).
Firstly, trifluoromethanethiol copper (I) was added to a mixture of 150 mg of 4-(5-iodo-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 1.5 mL of 1,3-dimethyl-2-imidazolidine at room temperature. After completion of the addition, the reaction mixture was stirred at 130° C. for three hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with 10 mL of ethyl acetate. The resultant filtrate was washed with 10 mL of aqueous saturated ammonium chloride solution and 5 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=10:90 to 30:70), to thereby yield 126 mg of the target product as a pale yellow solid.
Melting point: 152-155° C.
1H NMR: δ 7.87 (d, J=8.4 Hz, 1H), 7.75 (d, J=1.8 Hz, 1H), 7.55-7.62 (m, 1H), 7.30-7.38 (m, 2H), 6.86-6.98 (m, 2H), 3.74 (s, 3H), 3.72 (s, 3H), 3.36 (s, 3H), 2.13 (s, 3H).
Firstly, a mixture of 110 mg of 5-methoxy-4-(2-(2-methoxyphenyl)-5-((trifluoromethyl)thio)benzo[b]thiophen-3-yl)-2,6-di methylpyridazin-3(2H)-one and 1.5 mL of morpholine was stirred at 100° C. for seven hours. After completion of the stirring, 5 mL of water was added to the reaction mixture, and 35% by mass hydrochloric acid was added to the mixture under ice cooling so as to achieve a pH of 1. After completion of the addition, the resultant mixture was subjected to extraction with 15 mL of ethyl acetate. The resultant organic phase was washed with 5 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Subsequently, 5 mL of diisopropyl ether was added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 65 mg of the target product as a white solid.
Melting point: 183-186° C.
1H NMR: δ 7.89 (d, J=8.1 Hz, 1H), 7.60-7.70 (m, 2H), 7.28-7.42 (m, 2H), 6.94-7.00 (m, 2H), 6.33 (brs, 1H), 3.81 (s, 3H), 3.74 (s, 3H), 2.20 (s, 3H).
Synthesis of 6-chloro-5-hydroxy-4-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-2-methylpyridazin-3(2H)-one (Compound No. 3-088)
Firstly, a mixture of 1.3 g of ethyl 2-(2-methylhydrazinylidene)acetate and 10 mL of N,N-dimethylformamide was heated to 50° C., and 1.5 g of N-chlorosuccinimide was added to the mixture at 50° C. After completion of the addition, the reaction mixture was stirred at 50 to 60° C. for three hours. After completion of the stirring, 30 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with tert-butyl methyl ether (30 mL×2). The resultant organic phase was washed with 30 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Subsequently, 10 mL of tert-butyl methyl ether and 1.0 g of dibenzylamine were added to the resultant residue at room temperature. After completion of the addition, the reaction mixture was cooled to 0° C., and 1.1 g of 1,8-diazabicyclo[5,4,0]-7-undecene was added to the mixture at 0° C. After completion of the addition, the reaction mixture was stirred at room temperature for 18 hours. After completion of the stirring, 30 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with ethyl acetate (30 mL×2). The resultant organic phase was washed with 30 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=5:95 to 10:90), to thereby yield 714 mg of the target product as a colorless oily product.
1H NMR: δ 7.02-7.34 (m, 10H), 4.26 (q, 7.2 Hz, 2H), 4.02 (s, 4H), 2.86 (d, J=4.2 Hz, 3H), 1.31 (t, J=7.2 Hz, 3H).
Firstly, 458 mg of oxalyl chloride and 10 mg of N,N-dimethylformamide were added to a mixture of 790 mg of 2-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)acetic acid produced in step 2 of Synthesis Example 3 and 8 mL of dichloromethane at room temperature. After completion of the addition, the reaction mixture was stirred at room temperature for two hours. After completion of the stirring, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in 10 mL of toluene, and 712 mg of ethyl 2-(dibenzylamino)-2-(2-methylhydrazinylidene)acetate and 243 mg of pyridine were added to the solution. After completion of the addition, the resultant mixture was stirred at 100° C. for one hour. After completion of the stirring, 30 mL of water was added to the mixture, and the resultant mixture was subjected to extraction with ethyl acetate (50 mL×2). The resultant organic phase was washed with 20 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=5:95 to 50:50), to thereby yield 743 mg of the target product as a yellow oily product.
1H NMR: δ 7.57 (d, J=8.7 Hz, 1H), 7.49 (dd, J=7.5, 1.5 Hz, 1H), 7.25-7.28 (m, 9H), 7.18-7.20 (m, 3H), 6.91-6.99 (m, 3H), 4.32 (brs, 4H), 4.28 (q, J=7.2 Hz, 2H), 3.85 (s, 3H), 3.78 (s, 3H), 3.73 (s, 2H), 3.14 (s, 3H), 1.22 (t, J=7.2 Hz, 3H).
Firstly, a mixture of 743 mg of ethyl 2-(dibenzylamino)-2-(2-(2-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)acetyl 1)-2-methylhydrazinylidene)acetate and 5 mL of tetrahydrofuran was cooled to 0° C., and 387 mg of potassium tert-butoxide was added to the mixture at 0° C. After completion of the addition, the reaction mixture was stirred at 0° C. for one hour. After completion of the stirring, 5 mL of 1 mol/L hydrochloric acid and 20 mL of water were added to the mixture, and then the precipitated solid was recovered through filtration. The resultant solid was washed sequentially with 5 mL of water and 5 mL of diisopropyl ether, to thereby yield 576 mg of the target product as a yellow solid.
Melting point: 163-166° C.
1H NMR: δ 7.24-7.35 (m, 10H), 7.08-7.11 (m, 4H), 6.95-7.00 (m 2H), 6.88 (d, J=7.8 Hz, 1H), 6.57 (brs, 1H), 4.00-4.30 (m, 4H), 3.88 (s, 3H), 3.69 (s, 3H), 3.58 (s, 3H).
Firstly, 550 mg of 5% palladium carbon (available from N.E.CHEMCAT CORPORATION, STD type, 50% hydrous product) was added to a mixture of 549 mg of 6-(dibenzylamino)-5-hydroxy-4-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-2-methylpyridazin-3(2H)-one, 5 mL of methanol, and 0.5 mL of 35% by mass hydrochloric acid, and the reaction container was purged with hydrogen gas. After completion of the hydrogen gas purging, the reaction mixture was stirred at room temperature for 20 hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with 10 mL of methanol. The resultant filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=50:50 to 100:0), to thereby yield 260 mg of the target product as a white solid.
Melting point: 286-288° C.
1H NMR: δ 7.30-7.38 (m, 4H), 6.97-7.01 (m, 3H), 6.56 (s, 1H), 4.15 (brs, 2H), 3.88 (s, 3H), 3.82 (s, 3H), 3.63 (s, 3H).
Firstly, a mixture of 242 mg of 6-amino-5-hydroxy-4-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-2-methyl pyridazin-3(2H)-one, 3 mL of acetonitrile, and 2 mL of 35% by mass hydrochloric acid was cooled to 0° C., and 110 mg of sodium nitrite was added to the mixture. After completion of the addition, the resultant mixture was stirred at room temperature for five hours. After completion of the stirring, 30 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with ethyl acetate (30 mL×2). The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=30:70 to 70:30), to thereby yield 51 mg of the target product as a white solid.
Melting point: 209-211° C.
1H NMR: δ 7.28-7.40 (m, 4H), 6.95-7.02 (m, 3H), 6.73 (brs, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.75 (s, 3H).
Firstly, 8.5 g of N-bromosuccinimide was added to a mixture of 12.9 g of ethyl 2-(6-methoxybenzo[b]thiophen-3-yl)acetate and 70 mL of acetonitrile under ice cooling, and the resultant mixture was stirred under ice cooling for one hour. After completion of the stirring, the solvent was distilled off under reduced pressure. Subsequently, 200 mL of aqueous saturated ammonium chloride solution was added to the resultant residue, and the resultant mixture was subjected to extraction with ethyl acetate (200 mL×2). The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, to thereby yield 12.1 g of the target product as a brown solid. This product was used in the next step without further purification.
Melting point: 143-148° C.
1H NMR: δ 7.53-7.58 (m, 1H), 7.18-7.22 (m, 1H), 6.95-7.05 (m, 1H), 4.16 (q, J=7.2 Hz, 2H), 3.82 (s, 2H), 3.86 (s, 3H), 1.24 (t, J=7.2 Hz, 3H).
Firstly, 60 mL of 1 mol/L dichloromethane solution of boron tribromide was added dropwise under ice cooling to a mixture of 12.1 g of ethyl 2-(2-bromo-6-methoxybenzo[b]thiophen-3-yl)acetate and 100 mL of dichloromethane, and the resultant mixture was stirred under ice cooling for one hour. After completion of the stirring, the reaction mixture was poured into 200 mL of water cooled at 0° C., and then the precipitated solid was recovered through filtration. The resultant solid was washed with 50 mL of water and 50 mL of diisopropyl ether. Subsequently, 8.4 g of potassium carbonate and 8.5 g of benzyl bromide were added to a mixture of the resultant solid and 30 mL of N,N-dimethylformamide at room temperature, and the resultant mixture was stirred at room temperature overnight. After completion of the stirring, 100 mL of water was added to the resultant mixture, and the mixture was subjected to extraction with a mixed solvent of 100 mL of diethyl ether and 100 mL of ethyl acetate. The resultant organic phase was washed with 100 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Diisopropyl ether was added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 9.2 g of the target product as a pale orange solid.
Melting point: 103-105° C.
1H NMR: δ 7.53-7.58 (m, 1H), 7.30-7.45 (m, 5H), 7.25-7.28 (m, 1H), 7.03-7.08 (m, 1H), 5.11 (s, 2H), 4.15 (q, J=7.2 Hz, 2H), 3.79 (s, 2H), 1.23 (t, J=7.2 Hz, 3H).
Firstly, 18 mL of 10% by mass aqueous sodium hydroxide solution was added to a mixture of 9.2 g of ethyl 2-(6-(benzyloxy)-2-bromobenzo[b]thiophen-3-yl)acetate, 30 mL of methanol, and 30 mL of tetrahydrofuran under ice cooling. After completion of the addition, the reaction mixture was stirred at room temperature for 18 hours. After completion of the stirring, the organic solvent was distilled off under reduced pressure, and 20 mL of 35% by mass hydrochloric acid was added to the resultant residue under ice cooling. After completion of the addition, the precipitated solid was recovered through filtration, and then washed with 50 mL of water, to thereby yield 8.5 g of the target product as a white solid.
Melting point: 170-172° C.
1H NMR (DMSO-d6): δ 12.56 (brs, 1H), 7.60-7.70 (m, 2H), 7.25-7.50 (m, 5H), 7.11 (dd, J=8.8, 2.3 Hz, 1H), 5.16 (s, 2H), 3.79 (s, 2H).
Firstly, 4.3 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 4.2 g of pentafluorophenol were added to a mixture of 8.5 g of 2-(6-(benzyloxy)-2-bromobenzo[b]thiophen-3-yl)acetic acid and 50 mL of dichloromethane at room temperature. After completion of the addition, the resultant mixture was stirred at room temperature for 18 hours. In another reaction container, 6.9 g of triethylamine was added dropwise to a mixture of 6.5 g of methylhydrazine sulfate and 50 mL of dichloromethane under ice cooling. After completion of the dropwise addition, the resultant mixture was stirred under ice cooling for one hour. After completion of the stirring, the previously prepared mixture of 2-(6-(benzyloxy)-2-bromobenzo[b]thiophen-3-yl)acetic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and pentafluorophenol was added dropwise to the reaction mixture under ice cooling. After completion of the dropwise addition, the resultant mixture was stirred at room temperature for 18 hours. After completion of the stirring, 100 mL of water was added to the reaction mixture at room temperature, and the resultant mixture was subjected to extraction with 100 mL of dichloromethane. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
The resultant residue was dissolved in 50 mL of ethanol, and 5.2 g of ethyl pyruvate was added to the solution at room temperature. After completion of the addition, the resultant mixture was stirred at 70° C. for two hours. After completion of the stirring, the solvent was distilled off from the reaction mixture under reduced pressure. Subsequently, 100 mL of water was added to the resultant residue, and the resultant mixture was subjected to extraction with 100 mL of diethyl ether. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
The resultant residue was dissolved in 50 mL of acetonitrile, and 2.6 g of 1,8-diazabicyclo[5.4.0]-7-undecene was added to the solution at room temperature, followed by stirring at 80° C. for six hours. After completion of the stirring, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in 50 mL of ethyl acetate, and 35 mL of 1 mol/L hydrochloric acid and 15 mL of water were added to the solution under ice cooling, followed by separation of the organic phase and the aqueous phase. The resultant aqueous phase was subjected to extraction with ethyl acetate (50 mL×2). The resultant organic phases were combined, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, to thereby yield 2.6 g of the crude target product as a brown amorphous product. This product was used in the next step without further purification.
1H NMR: δ 7.10-7.50 (m, 7H), 7.02 (dd, J=9.0, 2.5 Hz, 1H), 5.97 (brs, 1H), 5.12 (s, 2H), 3.75 (s, 3H), 2.35 (s, 3H).
Firstly, 2.4 g of potassium carbonate and 1-6 g of iodomethane were added to a mixture of 2.6 g of 4-(6-(benzyloxy)-2-bromobenzo[b]thiophen-3-yl)-5-hydroxy-2,6-dimethylpyridazin-3(2H)-one and 10 mL of N,N-dimethylformamide. After completion of the addition, the resultant mixture was stirred at room temperature for 18 hours. After completion of the stirring, 50 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with 50 mL of ethyl acetate. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=5:95 to 25:75), to thereby yield 1.8 g of the target product as a pale yellow solid.
Melting point: 167-169° C.
1H NMR: δ 7.25-7.50 (m, 7H), 7.04 (dd, J=8.9, 2.4 Hz, 1H), 5.11 (s, 2H), 3.75 (s, 3H), 3.43 (s, 3H), 2.32 (s, 3H).
Firstly, 2.5 g of potassium phosphate, 1.2 g of (2-methoxyphenyl)boronic acid, and 450 mg of tetrakis(triphenylphosphine)palladium were added to a mixture of 1.2 g of 4-(6-(benzyloxy)-2-bromobenzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 15 mL of toluene. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 100° C. for two hours. After completion of the stirring, insoluble matter was filtered with celite. The resultant filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=10:90 to 50:50), to thereby yield 1.9 g of the target product as a dark red amorphous product.
1H NMR: δ 7.28-7.48 (m, 9H), 7.04-7.10 (m, 1H), 6.68-7.02 (m, 2H), 5.14 (s, 2H), 3.74 (s, 3H), 3.70 (s, 3H), 3.37 (s, 3H), 2.10 (s, 3H).
Firstly, 1.9 g of 5% palladium carbon (available from N.E.CHEMCAT CORPORATION, STD type, 50% hydrous product) was added to a mixture of 1.9 g of 4-(6-(benzyloxy)-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one, 40 mL of methanol, and 20 mL of tetrahydrofuran. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction container was purged with hydrogen gas. After completion of the hydrogen gas purging, the reaction mixture was stirred at room temperature for 48 hours. After completion of the stirring, the palladium carbon was separated through filtration with celite, and the residue was washed with 100 mL of chloroform. The solvent was distilled off from the resultant filtrate under reduced pressure, to thereby yield 1.5 g of the target product as a pale yellow solid.
1H NMR: δ 7.74 (s, 1H), 7.27-7.40 (m, 2H), 7.03-7.11 (m, 1H), 6.82-6.99 (m, 2H), 6.68-6.73 (m, 1H), 6.56-6.61 (m, 1H), 3.81 (s, 3H), 3.71 (s, 3H), 3.45 (s, 3H), 2.13 (s, 3H).
Firstly, 200 mg of potassium carbonate and 340 mg of 2,2,2-trifluoroethyl trifluoromethanesulfonate were added to a mixture of 200 mg of 4-(6-hydroxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 3 mL of acetonitrile at room temperature. After completion of the addition, the reaction mixture was stirred at room temperature for 18 hours. After completion of the stirring, insoluble matter was filtered with celite, and the resultant filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=5:95 to 25:75), to thereby yield 162 mg of the target product as a colorless oily product.
1H NMR: δ 7.24-7.44 (m, 4H), 7.03 (dd, J=8.9, 2.4 Hz, 1H), 6.83-6.95 (m, 2H), 4.40 (q, J=8.2 Hz, 2H), 3.73 (s, 3H), 3.69 (s, 3H), 3.35 (s, 3H), 2.09 (s, 3H).
Firstly, 1 mL of morpholine was added to a mixture of 162 mg of 5-methoxy4-(2-(2-methoxyphenyl)-6-(2,2,2-trifluoroethoxy)benzo[b]thiophen-3-yl)-2,6-di methylpyridazin-3(2H)-one and 3 mL of N-methyl-2-pyrrolidone at room temperature, and the resultant mixture was stirred at 100° C. for three hours. After completion of the stirring, 20 mL of 1 mol/L hydrochloric acid was added to the reaction mixture under ice cooling, and the resultant mixture was subjected to extraction with ethyl acetate (30 mL×2). The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Subsequently, 2 mL of diisopropyl ether was added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 19 mg of the target product as a white solid.
Melting point: 216-218° C.
1H NMR: δ 7.35-7.40 (m, 3H), 7.27-7.34 (m, 1H), 7.01-7.07 (m, 1H), 6.91-6.99 (m, 2H), 4.42 (q, J=8.2 Hz, 2H), 3.81 (s, 3H), 3.74 (s, 3H), 2.18 (s, 3H).
Firstly, 33 mg of N-chlorosuccinimide was added to a mixture of 100 mg of 4-(6-methoxy-2-(2-methoxyphenyl)benzo[b]thiophen-3-yl)-5-hydroxy-2,6-dimethylpyridazin-3-(2H)-one and 3 mL of N,N-dimethylformamide at room temperature. After completion of the addition, the reaction mixture was stirred at 80° C. for one hour. After completion of the stirring, 10 mL of 1 mol/L hydrochloric acid was added to the reaction mixture under ice cooling, and the resultant mixture was subjected to extraction with 20 mL of ethyl acetate. The resultant organic phase was washed with 5 mL of 1 mol/L hydrochloric acid, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=5:95 to 30:70), to thereby yield 75 mg of the target product as a white solid.
Melting point: 229-231° C.
1H NMR: δ 7.25-7.40 (m, 3H), 7.06 (d, J=8.5 Hz, 1H), 6.90-7.00 (m, 2H), 6.45 (brs, 1H), 3.97 (s, 3H), 3.82 (s, 3H), 3.73 (s, 3H), 2.17 (s, 3H).
Firstly, 872 mg of p-benzyloxyphenylboronic acid, 1-6 g of potassium phosphate, and 294 mg of tetrakis(triphenylphosphine)palladium were added to a mixture of 890 mg of 4-(2-bromobenzofuran-3-yl)-5-methoxy-2,6-dimethylpyridazin-3-(2H)-one and 20 mL of toluene at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 110° C. for three hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with chloroform (10 mL×2). The resultant filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=5:95 to 25:75), to thereby yield 1.3 g of the target product as a pale yellow oily product.
1H NMR: δ 7.60-7.70 (m, 2H), 7.20-7.55 (m, 9H), 6.95-7.05 (m, 2H), 5.08 (s, 2H), 3.76 (s, 3H), 3.48 (s, 3H), 2.32 (s, 3H).
Firstly, 650 mg of 10% palladium carbon (available from N.E.CHEMCAT CORPORATION, PE type, 50% hydrous product) was suspended in 20 mL of tetrahydrofuran, and 1.3 g of 4-(2-(4-(benzyloxy)phenyl)benzofuran-3-yl)-5-methoxy-2,6-dimethylpyridazin-3-(2H)-one was added to the suspension at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction container was purged with hydrogen gas. After completion of the hydrogen gas purging, the reaction mixture was stirred at room temperature for three hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with chloroform (20 mL×2). The resultant filtrate was concentrated under reduced pressure. Subsequently, 40 mL of diisopropyl ether was added to the resultant residue, and then the precipitated solid was recovered through filtration, to thereby yield 770 mg of the target product as a white solid.
Melting point: 251-253° C.
1H NMR: δ 7.10-7.55 (m, 6H), 6.55-6.60 (m, 2H), 3.82 (brs, 3H), 3.54 (s, 3H), 2.37 (brs, 3H).
Firstly, 86 mg of potassium carbonate and 69 mg of 1-bromo-2-methoxyethane were added to a mixture of 150 mg of 4-(2-(4-hydroxyphenyl)benzofuran-3-yl)-5-methoxy-2,6-dimethylpyridazin-3-(2H)-one and 3 mL of acetonitrile at room temperature. After completion of the addition, the reaction mixture was stirred at 90° C. for three hours. After completion of the stirring, 5 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with 10 mL of ethyl acetate. The resultant organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (with a gradient of ethyl acetate:n-hexane=5:95 to 30:70), to thereby yield 148 mg of the target product as a colorless oily product.
1H NMR: δ 7.60-7.70 (m 2H), 7.50-7.55 (m, 1H), 7.15-7.35 (m, 3H), 6.90-7.00 (m, 2H), 4.10-4.20 (m, 2H), 3.70-3.80 (m, 5H), 3.48 (s, 3H), 3.46 (s, 3H), 2.32 (s, 3H). Step 4: Synthesis of 5-hydroxy-4-(2-(4-(2-methoxyethoxy)phenyl)benzofuran-3-yl)-2,6-dimethylpyridazin-3-(2H)-one (Compound No. 8-007)
Firstly, 1 mL of morpholine was added to a mixture of 148 mg of 5-methoxy-4-(2-(4-(2-methoxyethoxy)phenyl)benzofuran-3-yl)-2,6-dimethylpyridazin-3-(2H)-one and 1 mL of N-methyl-2-pyrrolidone at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 100° C. for six hours. After completion of the stirring, 1 mol/L hydrochloric acid was added to the mixture under ice cooling so as to achieve a pH of 1, and the resultant mixture was subjected to extraction with 20 mL of ethyl acetate. The resultant organic phase was washed with 1 mol/L hydrochloric acid (5 mL×2), and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then the resultant residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=20:80 to 75:25), to thereby yield 78 mg of the target product as a white solid.
Melting point: 214-216° C.
1H NMR: δ 7.50-7.65 (m, 3H), 7.15-7.35 (m, 3H), 6.85-6.95 (m, 2H), 5.96 (brs, 1H), 4.10-4.15 (m, 2H), 3.70-3.80 (m, 5H), 3.43 (s, 3H), 2.30 (s, 3H).
Firstly, 86 mg of p-methoxyphenylboronic acid, 240 mg of potassium phosphate, and 44 mg of tetrakis(triphenylphosphine)palladium were added to a mixture of 160 mg of 5-(2-bromo-5-fluorobenzofuran-3-yl)-1,3-dimethyl-6-oxo-1,6-dihydropyridazin-4-yl=(n-butyrate) and 6 mL of toluene at room temperature. After completion of the addition, the reaction container was purged with nitrogen gas. After completion of the nitrogen gas purging, the reaction mixture was stirred in a nitrogen atmosphere at 110° C. for three hours. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with chloroform (10 mL×2). The resultant filtrate was concentrated under reduced pressure, and then the residue was purified by silica gel chromatography (with a gradient of ethyl acetate:n-hexane=5:95 to 20:80), to thereby yield 53 mg of the target product as a pale yellow oily product.
1H NMR: δ 7.65-7.75 (m, 2H), 7.35-7.45 (m, 1H), 6.85-7.05 (m, 4H), 3.83 (s, 3H), 3.80 (s, 3H), 2.29 (s, 3H), 2.00-2.25 (m, 2H), 1.20-1.40 (m, 2H), 0.59 (t, J=7.5 Hz, 3H).
Firstly, a solution of 50 mg of lithium hydroxide in 1 mL of water was added to a mixture of 53 mg of 5-(5-fluoro-2-(4-methoxyphenyl)benzofuran-3-yl)-1,3-dimethyl-6-oxo-1,6-dihydropyridazin-4-yl=(n-butyrate) and 2 mL of tetrahydrofuran at room temperature. After completion of the addition, the reaction mixture was stirred at room temperature for one hour. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure. Subsequently, 35% by mass hydrochloric acid was added to the resultant residue so as to achieve a pH of 1, and then the precipitated solid was recovered through filtration, to thereby yield 39 mg of the target product as a white solid.
Melting point: 248-250° C.
1H NMR: δ 7.60-7.70 (m, 2H), 7.40-7.50 (m, 1H), 6.85-7.05 (m, 4H), 3.82 (s, 3H), 3.77 (s, 3H), 2.33 (s, 3H).
The compound of the present invention can be produced according to the aforementioned production methods and Examples. Pyridazinone compounds produced in the same manner as in Synthesis Examples 1 to 13, which are included in the compound of the present invention, will be shown in Tables 3 to 13, and exemplary production intermediates of the pyridazinone compounds will be shown in Table 14. The pyridazinone compounds included in the present invention and the intermediates of the compounds are not limited to those shown below.
In the following Tables, Me denotes methyl; n-Pr and Pr-n, normal propyl; i-Pr and Pr-i, isopropyl; c-Pr and Pr-c, cyclopropyl; n-Bu and Bu-n, normal butyl; i-Bu and Bu-i, isobutyl; t-Bu and Bu-t, tertiary butyl; n-Pen and Pen-n, normal pentyl; c-Pen and Pen-c, cyclopentyl; n-Hex and Hex-n, normal hexyl; c-Hex and Hex-c, cyclohexyl; Ph, phenyl; and Bn, benzyl. In the following Tables, the symbol “=” denotes a double bond, and the symbol “≡” denotes a triple bond.
In the following Tables, the expression “m.p.” denotes a melting point. The expression “*1” in the column of melting point refers to the case where the corresponding compound is in an oily form or a resin form.
D-1, D-2, D-3, D-4, D-5, D-6, D-7, D-8, D-9, D-10, D-11, D-12, D-13, D-14, D-15, D-16, D-17, D-18, D-19a, D-20a, D-21a, D-22a, D-23, D-24a, D-25, D-26, D-27, and D-28 in the Tables correspond to the following structures.
The expression “(Y1)” in the Tables refers to (Y1)p7, (Y1)p6, (Y1)p5, (Y1)P4, (Y1)P3, or (Y1)p7 corresponding to each of the aforementioned structures of D-1 to D-28 specified in the column of R3. The substitution position number corresponds to the numbered position in each of the aforementioned structural formulae. The expression “−” in the column of “(Y1)” refers to no substitution.
U-1a to U-6a, Q-1, Q-2a to Q-4a, Q-17a, Q-17b, and T-1-1 to T-3 in the Tables correspond to the following structures.
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Table 15 shows the spectrum data of compounds (among the compounds shown in Tables 3 to 14) whose melting points are not described in the Tables.
1H NMR
Firstly, 1.00 g of benzo[b]thiophene-3-boronic acid, 2.39 g of potassium phosphate, 350 mg of 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl, and 84 mg of palladium acetate were added to a mixture of 873 mg of 4-bromo-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 7.5 mL of toluene at room temperature. After completion of the addition, air in the reaction container was replaced with nitrogen gas. After completion of the gas replacement, the reaction mixture was stirred at 90° C. for four hours. After completion of the stirring, 10 mL of water and 10 mL of ethyl acetate were added to the reaction mixture, and insoluble matter was filtered with celite. The residue was washed with ethyl acetate (10 mL×2). The organic phase was separated from the resultant filtrate, and the resultant organic phase was washed with water (10 mL×1). Thereafter, the organic phase was dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel chromatography (elution with a gradient of ethyl acetate:n-hexane=5:95 to 20:80), to thereby yield 1.05 g of the target product as a yellow oily product.
1H NMR: δ 7.80-7.90 (m, 1H), 7.61 (s, 1H), 7.50-7.55 (m, 1H), 7.30-7.40 (m, 2H), 3.75 (s, 3H), 3.26 (s, 3H), 2.31 (s, 3H).
Firstly, 746 mg of N-bromosuccinimide was added to a mixture of 1.0 g of 4-(benzo[b]thiophen-3-yl)-5-methoxy-2,6-dimethylpyridazin-3(2H)-one and 5 mL of N,N-dimethylformamide at room temperature. After completion of the addition, the reaction mixture was stirred at 80° C. for two hours. After completion of the stirring, 20 mL of 1 mol/L aqueous sodium hydroxide solution was added to the reaction mixture, and the resultant mixture was subjected to extraction with 60 mL of diethyl ether. The resultant organic phase was washed with water (10 mL×1), and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (elution with a gradient of ethyl acetate:n-hexane=2:98 to 20:80), to thereby yield 962 mg of the target product as a white solid.
Melting point: 250-252° C.
1H NMR: δ 7.70-7.80 (m, 1H), 7.30-7.45 (m, 3H), 3.77 (s, 3H), 3.42 (s, 3H), 2.34 (s, 3H).
Firstly, a mixture of 32.3 g of potassium carbonate, 120 mL of N,N-dimethylformamide, and 25.0 g of 4-fluorobenzenethiol was cooled with ice, and ethyl 4-chloroacetoacetate was added dropwise to the mixture under ice cooling over one hour. After completion of the dropwise addition, the reaction mixture was stirred under ice cooling for one hour. After completion of the stirring, 250 mL of water was added to the reaction mixture, and the resultant mixture was subjected to extraction with 200 mL of toluene. The resultant organic phase was washed with 100 mL of water and 50 mL of aqueous saturated ammonium chloride solution, and then dehydrated and dried with anhydrous sodium sulfate. Thereafter, the solvent was distilled off under reduced pressure, to thereby yield a residue. The resultant residue was added dropwise under ice cooling over one hour to a suspension of 78.0 g of aluminum trichloride and 200 mL of 1,2-dichloroethane prepared in another reaction container. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 16 hours. After completion of the stirring, the reaction mixture was added dropwise over one hour to a mixture of 500 mL of ice and 100 mL of 1,2-dichloroethane. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for two hours. After completion of the stirring, the organic phase was separated from the reaction mixture. The resultant organic phase washed with 200 mL of water, and then dehydrated and dried sequentially with saturated salt water and anhydrous sodium sulfate, followed by addition of 4.0 g of powdery activated carbon. After completion of the addition, the resultant suspension was stirred at room temperature for 30 minutes. After completion of the stirring, insoluble matter was filtered with celite, and the residue was washed with chloroform (50 mL×2). The solvent was distilled off under reduced pressure, to thereby yield 32.5 g of the target product as a brown oily product. This product was used in the next step without further purification.
1H NMR: δ 7.77 (dd, J=8.9, 4.9 Hz, 1H), 7.40-7.50 (m, 2H), 7.12 (ddd, 8.9, 8.9, 2.5 Hz, 1H), 4.18 (q, J=7.2 Hz, 2H), 3.81 (s, 2H), 1.27 (t, J=7.2 Hz, 3H).
Firstly, a solution of 13.5 g of potassium hydroxide in 100 mL of water was added to a mixture of 32.5 g of ethyl 2-(5-fluorobenzo[b]thiophen-3-yl)acetate, 150 mL of tetrahydrofuran, and 50 mL of ethanol at room temperature. After completion of the addition, the reaction mixture was stirred at room temperature for 18 hours. After completion of the stirring, the solvent contained in the reaction mixture was distilled off under reduced pressure, and 100 mL of water was added to the resultant residue. The resultant mixture was washed sequentially with 100 mL of toluene and 50 mL of hexane. After completion of the washing, 35% by mass hydrochloric acid was added to the resultant mixture under ice cooling so as to achieve a pH of 1, and the precipitated solid was recovered through filtration. The resultant solid was washed with water (50 mL×2), to thereby yield 27.5 g of the target product as a white solid.
Melting point: 106-108° C.
1H NMR: δ 7.77 (dd, J=9.00, 4.9 Hz, 1H), 7.45 (s, 1H), 7.41 (dd, J=9.4, 2.5 Hz, 1H), 7.12 (ddd, J=8.8, 8.8, 2.5 Hz, 1H), 3.85 (s, 2H).
The usefulness of the compound of the present invention as herbicide will next be described in detail with reference to the following Test Examples. However, the present invention should not be construed as being limited to these Examples.
After alluvial soil was placed into 1/10000 are of Wagner pot, water was poured and mixed to form a submerged condition having a water depth of 4 cm. Seeds of late watergrass, Japanese bulrush, and oval-leafed pondweed were sowed in a mixed manner in the aforementioned pot, and then 2.5 leaf stage rice plant seedlings were transplanted thereto. On the day of sowing seeds, the emulsion agent of the compound of the present invention prepared according to Formulation Example 2 was diluted with water so as to achieve a predetermined herbicide amount, and the diluted emulsion agent was applied to the surface of the water. The pot was placed in a greenhouse at 25° C. to 30° C. for growth of the plants. Three weeks after the herbicide application, the effect of the herbicide on each plant was evaluated according to the following criteria. The results are shown in Table 16.
Evaluation Criteria
5: Herbicidal rate of 90% or more (almost completely withered)
4: Herbicidal rate of 70% or more and less than 90%
3: Herbicidal rate of 40% or more and less than 70%
2: Herbicidal rate of 20% or more and less than 40%
1: Herbicidal rate of 5% or more and less than 20%
0: Herbicidal rate of 5% or less (almost no effect)
After alluvial soil was placed into 1/10000 are of Wagner pot, water was poured and mixed to form a submerged condition having a water depth of 4 cm. Seeds of late watergrass, Japanese bulrush, and oval-leafed pondweed were sowed in a mixed manner in the aforementioned pot, and the pot was placed in a greenhouse at 25° C. to 30° C. for growth of the plants. When late watergrass, Japanese bulrush, and oval-leafed pondweed were grown to one leaf stage to two leaf stage, the emulsion agent of the compound of the present invention prepared according to Formulation Example 2 was diluted with water so as to achieve a predetermined herbicide amount, and the diluted emulsion agent was applied to the surface of the water. Three weeks after the herbicide application, the effect of the herbicide on each plant was evaluated according to the criteria of Test Example 1. The results are shown in Table 17.
After alluvial soil was placed into 1/10000 are of Wagner pot, water was poured and mixed to form a submerged condition having a water depth of 0.1 cm to 0.5 cm. Seeds of barnyard grass, Chinese sprangletop, rice flat sedge, and rice were sowed and the pot was placed in a greenhouse at 25° C. to 30° C. for growth of the plants. After 14-day growth of the plants, the emulsion agent of the compound of the present invention prepared according to Formulation Example 2 was diluted with water so as to achieve a predetermined herbicide amount, and the diluted emulsion agent was uniformly applied to a foliage part with a small-sized spray. Three weeks after the herbicide application, the effect of the herbicide on each plant was evaluated according to the criteria of Test Example 1. The results are shown in Table 18.
Sterilized diluvial soil was placed in a plastic box having a length of 21 cm, a width of 13 cm, and a depth of 7 cm. The seeds of each of southern crabgrass, green foxtail, barnyard grass, wild oat, blackgrass, Italian ryegrass, windgrass, velvetleaf, redroot pigweed, lambsquarters, chickweed, false cleavers, persian speedwell, corn, soybean, rice, wheat, beet, and rapeseed were sowed in a spot-like manner and covered with the soil having a thickness of about 1.5 cm. Subsequently, the emulsion agent of the compound of the present invention prepared according to Formulation Example 2 was diluted with water so as to achieve a predetermined herbicide amount, and the diluted emulsion agent was uniformly applied to the surface of the soil with a small-sized spray. The plastic box was placed in a greenhouse at 25° C. to 30° C. for growth of the plants. Three weeks after the herbicide application, the effect of the herbicide on each plant was evaluated according to the criteria of Test Example 1. The results are shown in Table 19.
Sterilized diluvial soil was placed in a plastic box having a length of 21 cm, a width of 13 cm, and a depth of 7 cm. The seeds of each of southern crabgrass, green foxtail, barnyard grass, wild oat, blackgrass, Italian ryegrass, windgrass, velvetleaf, redroot pigweed, lambsquarters, chickweed, false cleavers, persian speedwell, corn, soybean, rice, wheat, beet, and rapeseed were sowed in a spot-like manner and covered with the soil having a thickness of about 1.5 cm. Thereafter, the plants were grown in a greenhouse at 25° C. to 30° C. After 14-day growth of the plants, the emulsion agent of the compound of the present invention prepared according to Formulation Example 2 was diluted with water so as to achieve a predetermined herbicide amount, and the diluted emulsion agent was uniformly applied to a foliage part with a small-sized spray. Three weeks after the herbicide application, the effect of the herbicide on each plant was evaluated according to the criteria of Test Example 1. The results are shown in Table 20.
The symbols in Tables 16 to 20 have the following meanings.
A: late watergrass, B: Japanese bulrush, C: oval-leafed pondweed, D: Chinese sprangletop, E: rice flat sedge, F: southern crabgrass, G: green foxtail, H: barnyard grass, I: wild oat, J: blackgrass, K: Italian ryegrass, L: windgrass, M: velvetleaf, N: redroot pigweed, 0: lambsquarters, P: chickweed, Q: false cleavers, R: persian speedwell, a: transplanted rice, b: directly sowed rice, c: corn, d: soybean, e: wheat, f: beet, and g: rapeseed.
The term “amount of applied herbicide (g/ha)” refers to the case where the concentration is adjusted so that the herbicide is applied in a described amount (g) per hectare (ha).
The pyridazinone compound of the present invention is a novel compound and is very useful as a selective herbicide for rice, corn, soybean, wheat, beet, and rapeseed.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2019-070172 | Apr 2019 | JP | national |
| 2020-039961 | Mar 2020 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2020/015122 | 4/1/2020 | WO |
