Pyrimidine derivatives and herbicides containing them

TECHNICAL FIELD

The present invention relates to novel pyrimidine derivatives and herbicides containing them as active ingredients.

BACKGROUND ART

Pyrimidine derivatives are known, for example, by the specification of international application WO95/12582, the specification of international application WO96/22980 and the specification of international application WO97/12877. However, the pyrimidine derivatives of the present invention have not been known.

A herbicide to be used for crop plants is desired to be a chemical which exhibits a sufficient herbicidal effect at a low dose and yet provides selectivity between crop plants and weeds, when applied to an upland field or to a paddy field. Accordingly, it is an object of the present invention to provide a compound which has an excellent herbicidal activity and selectivity between crop plants and weeds.

DISCLOSURE OF THE INVENTION

Under these circumstances, the present inventors have synthesized various substituted pyrimidine derivatives and have studied their physiological activities. As a result, it has been found that novel substituted pyrimidine derivatives as the compounds of the present invention have excellent herbicidal activities and selectivity between crop plants and weeds, and the present invention has been accomplished. Namely, the present invention provides a pyrimidine derivative represented by the formula (I)

wherein R

1

is a hydrogen atom (except for a case where R

2

=hydrogen atom, and W═SO

2

), a halogen atom, a C

1

-C

6

alkyl group, a C

1

-C

6

alkylcarbonyl C

1

-C

6

alkyl group, a hydroxyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

3

-C

6

cycloalkyl group (this group may be substituted by a halogen atom, a C

1

-C

6

alkyl group, a C

1

-C

6

alkoxy group or a C

1

-C

4

haloalkyl group), a C

1

-C

4

haloalkyl group, a C

1

-C

6

alkoxy group, a C

1

-C

4

haloalkoxy group, a C

2

-C

6

alkenyloxy group, a C

2

-C

6

alkynyloxy group, a C

3

-C

6

cycloalkyloxy group, a phenyl group (this group may be substituted by a halogen atom, a C

1

-C

6

alkyl group, a C

1

-C

6

alkoxy group, a C

1

-C

4

haloalkyl group, a C

1

-C

4

haloalkoxy group, a cyano group, a cyano C

1

-C

6

alkyl group, a nitro group, a C

1

-C

6

alkylthio group, a C

1

-C

6

alkylsulfinyl group or a C

1

-C

6

alkylsulfonyl group), a C

1

-C

6

alkylthio group (except for a case where R

2

=phenyl group, and W═SO

2

), a C

2

-C

6

alkenylthio group, a C

2

-C

6

alkynylthio group, a C

3

-C

6

cycloalkylthio group, a C

1

-C

6

alkylsulfinyl group, a C

2

-C

6

alkenylsulfinyl group, a C

2

-C

6

alkynylsulfinyl group, a C

3

-C

6

cycloalkylsulfinyl group, a C

1

-C

6

alkylsulfonyl group, a C

2

-C

6

alkenylsulfonyl group, a C

2

-C

6

alkynylsulfonyl group, a C

3

-C

6

cycloalkylsulfonyl group, a C

1

-C

6

hydroxyalkyl group, a C

2

-C

7

acyl group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a cyano group, a C

1

-C

6

alkoxycarbonyl group, a C

1

-C

6

alkoxycarbonyl C

1

-C

6

alkyl group, a C

1

-C

6

alkoxycarbonyl C

2

-C

6

alkenyl group, a carboxyl group, a carboxyl C

1

-C

6

alkyl group, a di C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a C

1

-C

6

alkoxyimino C

1

-C

6

alkyl group, a hydroxyimino C

1

-C

6

alkyl group, a dioxolanyl group (this group may be substituted by a C

1

-C

6

alkyl group), an aldehyde group, an oxiranyl group, a NR

9

R

10

group or a CONR

9

R

10

group, R

9

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

4

haloalkyl group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a C

1

-C

6

alkylthio C

1

-C

6

alkyl group, a C

3

-C

6

cycloalkyl group, a C

2

-C

7

acyl group or a C

1

-C

6

alkylsulfonyl group, R

10

is a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

4

haloalkyl group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a C

1

-C

6

alkylthio C

1

-C

6

alkyl group, a C

3

-C

6

cycloalkyl group, a C

2

-C

7

acyl group, a C

1

-C

6

alkylsulfonyl group, a C

1

-C

6

alkoxycarbonyl group or a benzyloxycarbonyl group, here R

9

and R

10

may, together with the carbon atom to which they are bonded, form a 5- to 7-membered saturated ring, R

2

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

6

alkylthio group, a C

1

-C

4

haloalkyl group, a C

1

-C

6

alkoxy group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a C

1

-C

6

alkylthio C

1

-C

6

alkyl group, a C

3

-C

6

cycloalkyl group (this group may be substituted by a halogen atom, a C

1

-C

6

alkyl group, a C

1

-C

6

alkoxy group or a C

1

-C

4

haloalkyl group), a C

2

-C

7

acyl group, a cyano group, a di C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a C

1

-C

6

alkoxyimino C

1

-C

6

alkyl group, a hydroxyimino C

1

-C

6

alkyl group, a dioxolanyl group (this group may be substituted by a C

1

-C

6

alkyl group), a cyano C

1

-C

6

alkyl group, a C

1

-C

6

hydroxyalkyl group, a C

1

-C

6

alkoxycarbonyl group, a C

1

-C

6

alkoxycarbonyl C

1

-C

6

alkyl group, a CR

11

R

12

NR

9

R

10

group, a CONR

9

R

10

group, a CR

11

R

12

CONR

9

R

10

group or a group represented by any one of the formulae R

2

-1 to R

2

-13:

(wherein X is a hydrogen atom, a halogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

6

alkoxy group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a NR

9

R

10

group, a CONR

9

R

10

group, a C

1

-C

4

haloalkoxy group, a C

2

-C

6

alkenyloxy group, a C

3

-C

6

cycloalkyloxy group, a s C

2

-C

7

acyl group, a C

1

-C

6

alkoxycarbonyl group, a C

1

-C

6

alkylthio group, a C

1

-C

6

alkylsulfinyl group, a C

1

-C

6

alkylsufonyl group, a cyano group, a nitro group or a C

1

-C

4

haloalkyl group, n is an integer of from 1 to 3, when n is an integer of 2 or 3, the plurality of X may be the same or different, and two adjacent lower alkoxy groups may be bonded to each other to form a C

1

-C

3

alkylenedioxy group), each of R

11

and R

12

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group or a C

1

-C

6

alkoxy group, R

3

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

6

alkoxy group, a di C

1

-C

6

alkylamino group, a C

3

-C

6

cycloalkyl group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a cyano C

1

-C

6

alkyl group, a C

3

-C

6

cycloalkyl C

1

-C

6

alkyl group, an oxiranyl C

1

-C

6

alkyl group or a C

1

-C

6

alkoxycarbonyl C

1

-C

6

alkyl group, W is a —C(═Q)Z— group or a —SO

2

— group, Q is an oxygen atom or a sulfur atom, Z is an oxygen atom, a sulfur atom, a —NR

6

— group, a —CH

2

CH

2

— group, a —CH═CH— group, a —C(R

4

)R

5

— group, a —C(R

4

)R

5

—Q— group, a —Q—C(R

4

)R

5

— group, a —C(═Q)— group, a —NR

6

NR

6a

— group or a —NR

6

C(R

4

)R

5

— group, each of R

4

and R

5

is a hydrogen atom, a C

1

-C

6

alkyl group, a halogen atom, a C

1

-C

6

alkoxy group or a C

1

-C

6

alkylthio group, each of R

6

and R

6a

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group or a C

2

-C

6

alkynyl group, here R

3

and R

6

may, together with the carbon atom to which they are bonded, form a 5- to 7-membered cyclic urea, Ar is a group represented by any one of the formulae Ar-1 to Ar-17:

(wherein X′ is a hydrogen atom, a halogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

6

alkoxy group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a NR

9

R

10

group, a CONR

9

R

10

group, a C

1

-C

4

haloalkoxy group, a C

2

-C

6

alkenyloxy group, a C

3

-C

6

cycloalkyloxy group, a C

2

-C

7

acyl group, a C

1

-C

6

alkoxycarbonyl group, a C

1

-C

6

alkylthio group, a C

1

-C

6

alkylsulfinyl group, a C

1

-C

6

alkylsufonyl group, a cyano group, a nitro group or a C

1

-C

4

haloalkyl group, n′ is an integer of from 1 to 3, m is an integer of from 0 to 3, when n′ is an integer of 2 or 3, the plurality of X′ may be the same or different, and two adjacent lower alkoxy groups may be bonded to each other to form a C

1

-C

3

alkylenedioxy group), R

7

is a hydrogen atom, a halogen atom, a C

1

-C

6

alkyl group, a C

1

-C

6

alkoxy group, a C

1

-C

6

alkylthio group, a C

1

-C

4

haloalkyl group or a C

3

-C

6

cycloalkyl group, and R

8

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

1

-C

6

alkylthio group, a C

1

-C

4

haloalkyl group or a C

3

-C

6

cycloalkyl group; and a herbicide containing it as an active ingredient.

Now, definitions of terms used in this specification will be shown below.

The halogen atom represents a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

The C

1

-C

6

alkyl group means a straight chain or branched chain alkyl group having a carbon number of from 1 to 6, unless otherwise specified, and it may, for example, be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group.

The C

3

-C

6

cycloalkyl group represents a cycloalkyl group having a carbon number of from 3 to 6, and it may, for example, be a cyclopropyl group, a cyclopentyl group or a cyclohexyl group.

The C

2

-C

6

alkenyl group represents a straight chain or branched chain alkenyl group having a carbon number of from 2 to 6, and it may, for example, be an ethenyl group or a 2-propenyl group.

The C

2

-C

6

alkynyl group represents a straight chain or branched chain alkynyl group having a carbon number of from 2 to 6, and it may, for example, be an ethynyl group or a 2-propynyl group.

The C

1

-C

4

haloalkyl group represents a straight chain or branched chain alkyl group having a carbon number of from 1 to 4, which is substituted by from 1 to 9 same or different halogen atoms, unless otherwise specified, and it may, for example, be a chloromethyl group, a trifluoromethyl group or a tetrafluoroethyl group.

The C

1

-C

6

alkoxy group represents an (alkyl)-O-group wherein the alkyl moiety has the above meaning, and it may, for example, be a methoxy group, an ethoxy group or a propoxy group.

The C

2

-C

6

alkenyloxy group represents an (alkenyl)-O-group wherein the alkenyl moiety has the above meaning, and it may, for example, be an ethenyloxy group or a 2-propenyloxy group.

The C

2

-C

6

alkynyloxy group represents an (alkynyl)-O-group wherein the alkynyl moiety has the above meaning, and it may, for example, be an ethynyloxy group or a 2-propynyloxy group.

The C

3

-C

6

cycloalkyloxy group represents a (cycloalkyl)-O-group wherein the cycloalkyl moiety has the above meaning, and it may, for example, be a cyclopropyloxy group, a cyclopentyloxy group or a cyclohexyloxy group.

The C

1

-C

6

alkoxy C

1

-C

6

alkyl group represents an (alkyl)-O-(alkylene)-group, wherein the alkyl moiety has the above meaning, and it may, for example, be a methoxymethyl group or an ethoxymethyl group.

The C

3

-C

6

cycloalkyl C

1

-C

6

alkyl group represents a (cycloalkyl)-(C

1

-C

6

alkylene) group wherein the cycloalkyl moiety has the above meaning, and it may, for example, be a cyclopropylmethyl group, a cyclopentylmethyl group, a cyclohexylmethyl group or a cyclohexylethyl group.

The C

1

-C

4

haloalkoxy group represents a (haloalkyl)-O-group wherein the haloalkyl moiety has the above meaning, and it may, for example, be a trifluoromethoxy group or a 2,2,2-trifluoroethoxy group.

The C

1

-C

6

alkylthio group, the C

1

-C

6

alkylsulfinyl group and the C

1

-C

6

alkylsulfonyl group, represent an (alkyl)-S-group, an (alkyl)-SO-group and an (alkyl)-SO

2

-group, wherein the alkyl moiety has the above meaning, and they may, for example, be a methylthio group, an ethylthio group, a methylsultinyl group, an ethylsulfinyl group, a methylsulfonyl group or an ethylsulfonyl group.

The C

2

-C

6

alkenylthio group, the C

2

-C

6

alkenylsulfinyl group and the C

2

-C

6

alkenylsulfonyl group, represent an (alkenyl)-S-group, an (alkenyl)-SO-group and an (alkenyl)-SO

2

-group, wherein the alkenyl moiety has the above meaning, and they may, for example, be a propenylthio group, a butenylthio group, a propenylsulfinyl group, a butenylsulfinyl group, a propenylsulfonyl group or a butenylsulfonyl group.

The C

2

-C

6

alkynylthio group, the C

2

-C

6

alkynylsulfinyl group and the C

2

-C

6

alkynylsulfonyl group, represent an (alkynyl)-S-group, an (alkynyl)-SO-group and an (alkynyl)-SO

2

-group, wherein the alkynyl moiety has the above meaning, and they may, for example, be an ethynylthio group, a 2-propynylthio group, an ethynylsulfinyl group, a 2-propynylsulfinyl group, an ethynylsulfonyl group or a 2-propynylsulfonyl group.

The C

3

-C

6

cycloalkylthio group, the C

3

-C

6

cycloalkylsulfinyl group and the C

3

-C

6

cycloalkylsulfonyl group, represent a (cycloalkyl)-S-group, a (cycloalkyl)-SO-group, and a (cycloalkyl)-SO

2

-group, wherein the cycloalkyl moiety has the above meaning, and they may, for example, be a cyclopropylthio group, a cyclobutylthio group, a cyclopentylthio group, a cyclohexylthio group, a cyclopropylsulfinyl group, a cyclobutylsulfinyl group, a cyclopentylsulfinyl group, a cyclohexylsulfinyl group, a cyclopropylsulfonyl group, a cyclobutylsulfonyl group, a cyclopentylsulfonyl group or a cyclohexylsulfonyl group.

The C

1

-C

6

alkylthio C

1

-C

6

alkyl group represents an (alkyl)-S-(alkylene) group wherein the alkyl moiety has the above meaning, and it may, for example, be a methylthiomethyl group, an ethylthiomethyl group, a propylthiomethyl group or a methylthioethyl group.

The C

2

-C

7

acyl group represents a C

1

-C

6

alkylcarbonyl group, a C

2

-C

6

alkenylcarbonyl group, a C

2

-C

6

alkynylcarbonyl group, a C

3

-C

6

cycloalkylcarbonyl group or a benzoyl group, and it may, for example, be an acetyl group, a propionyl group, a n-butyryl group, an isobutyryl group, a cyclopropylcarbonyl group or a benzoyl group.

The C

1

-C

6

alkylcarbonyl C

1

-C

6

alkyl group may, for example, be a methylcarbonylmethyl group, an ethylcarbonylmethyl group or a propylcarbonylmethyl group.

The diC

1

-C

6

alkoxy C

1

-C

6

alkyl group may, for example, be a dimethoxymethyl group or a diethoxymethyl group.

The C

1

-C

6

alkoxyimino C

1

-C

6

alkyl group may, for example, be a methoxyiminomethyl group or an ethoxyiminomethyl group.

The hydroxyimino C

1

-C

6

alkyl group may, for example, be a hydroxyiminomethyl group or a hydroxyiminoethyl group.

The cyano C

1

-C

6

alkyl group may, for example, be a cyanomethyl group or a cyanoethyl group.

The C

1

-C

6

hydroxyalkyl group may, for example, be a hydroxymethyl group or a hydroxyethyl group.

The C

1

-C

6

alkoxycarbonyl group may, for example, be a methoxycarbonyl group or an ethoxycarbonyl group.

The C

1

-C

6

alkoxycarbonyl C

1

-C

6

alkyl group may, for example, be a methoxycarbonyl methyl group or an ethoxycarbonyl methyl group.

The carboxyl C

1

-C

6

alkyl group may, for example, be a carboxymethyl group or a carboxyethyl group.

The diC

1

-C

6

alkoxy C

1

-C

6

alkyl group may, for example, be a diethoxymethyl group or a 2-dimethoxyethyl group.

The diC

1

-C

6

alkylamino group is a dialkylamino group wherein the alkylalkyl moiety has the above meaning, and it may, for example, be a dimethylamino group or a diethylamino group.

BEST MODE FOR CARRYING OUT THE INVENTION

Now, typical specific examples of the compound of the present invention represented by the formula (I) will be exemplified in Tables 1 to 39. However, the compound of the present invention is not limited to such compounds. The compound numbers will be referred to in the subsequent description. Further, in a case where the compound of the present invention or the disclosed compound has at least one asymmetric carbon, its all steric isomers are included in the compound of the present invention.

In the tables in this specification, S-isomer and R-isomer represent S-isomer and R-isomer of optical isomers, respectively, and in a case where there is no specific representation even when the compound has an asymmetric carbon, such represents a racemate. Further, in the tables, A-isomer and B-isomer represent diastereomers such that when resolved by silica gel column chromatography, one eluting first is designated as A-isomer, and one eluting later is designated as B-isomer. In a case where there is no representation even if diastereomers exist, such represents a mixture of diastereomers.

The following representations in the tables in this specification represent the respective corresponding groups as shown below.

Me: methyl group

Et: ethyl group

Pr: n-propyl group

Pr-i: isopropyl group

Pr-c: cyclopropyl group

Bu: n-butyl group

Bu-i: isobutyl group

Bu-s: sec-butyl group

Bu-t: tert-butyl group

Bu-c: cyclobutyl group

Pen: n-pentyl group

Pen-i: isopentyl group

Pen-c: cyclopentyl group

Hex-c: cyclohexyl group

TABLE 1

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Xn

Q

Diastereomer

(n

D

20

)

1-1

CClF

2

Pr-c

H

CH

2

H

O

124-127

1-2

CClF

2

Pr-c

H

CH

2

4-OMe

O

116-119

1-3

CClF

2

Pr-c

H

CH

2

4-Cl

O

125-128

1-4

CClF

2

Pr-c

H

CH

2

4-CF

3

O

111-114

1-5

CF

3

Pr-i

H

CH

2

H

O

144-146

1-6

CF

3

Pr-i

H

CH

2

4-OMe

O

114-117

1-7

CF

3

Pr-i

H

CH(Me)

H

O

1.5163

1-8

CF

3

Pr-i

Me

CH

2

H

O

106-109

1-9

CF

3

Pr-i

Me

CH

2

4-OMe

O

1.5289

1-10

CF

3

Pr-i

Me

S

H

O

131-133

1-11

CF

3

Pr-i

Me

S

4-OMe

O

156-159

1-12

CF

3

Pr-i

Me

CH

2

4-F

O

109-110

1-13

CF

3

Pr-i

Me

CH

2

4-OEt

O

1.5151

1-14

CF

3

Pr-i

Me

S

4-Cl

O

1-15

CClF

2

Pr-i

Me

CH

2

H

O

109-112

1-16

CClF

2

Pr-i

Me

CH

2

4-OMe

O

Not

Measurable

1-17

CClF

2

Pr-i

Me

S

H

O

127-130

1-18

CClF

2

Pr-i

Me

S

4-OMe

O

136-139

1-19

CClF

2

Pr-i

Me

O

H

O

115-118

1-20

CF

3

Pr-i

Me

CH

2

2-Cl

O

178-181

1-21

CF

3

Pr-i

Me

CH

2

3-Cl

O

122-125

1-22

CF

3

Pr-i

Me

CH

2

4-Cl

O

99-101

1-23

CF

3

Pr-i

Me

CH

2

4-Me

O

76-79

1-24

CF

3

Pr-i

Mo

CH

2

4-CF

3

O

105-108

1-25

CClF

2

Pr-i

Me

CH

2

4-F

O

126-129

1-26

CF

3

Pr-i

Et

CH

2

H

O

87-90

1-27

CF

3

Pr-i

Et

CH

2

4-F

O

130-132

1-25

CF

3

Pr-i

Me

NH

H

O

149-150

1-29

CF

3

Pr-i

Me

NH

4-Cl

O

TABLE 2

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-30

CF

3

Me

Me

CH

2

H

O

1.5258

1-31

CF

3

Me

Me

CH

2

4-F

O

1.5202

1-32

CF

3

Et

Me

CH

2

H

O

40-41

1-33

CF

3

Et

Me

CH

2

4-F

O

72-73

1-34

CF

3

Pr-c

Me

CH

2

H

O

Not Measurable

1-35

CF

3

Pr-c

Me

CH

2

4-F

O

97-99

1-36

CF

3

Ph

Me

CH

2

4-F

O

93-94

1-37

CClF

2

Pr-i

Me

NH

4-Me

O

135-137

1-38

CClF

2

Pr-i

Me

NH

H

O

146-147

1-39

CF

3

Pr-i

Me

CH

2

3-CF

3

O

119-120

1-40

CF

3

Pr-i

Me

CH

2

2,5-F

2

O

145-146

1-41

CF

3

Pr-i

Me

CH

2

4-Br

O

93-95

1-42

CF

3

Pr-i

Me

CH

2

4-I

O

102-104

1-43

CF

3

Pr-i

Me

CH

2

4-Bu-t

O

101-102

1-44

CF

3

Pr-i

Me

CH

2

4-SMe

O

69-71

1-45

CF

3

Pr-i

Me

CH

2

3,4-Cl

2

O

145-146

1-46

CF

3

Pr-i

Me

CH

2

2-F,4-Cl

O

115-116

1-47

CF

3

Pr-i

Me

CH

2

3-OMe,4-Cl

O

129-131

1-48

CF

3

Pr-i

Et

CH

2

4-Cl

O

120-123

1-49

CF

3

Pr-i

Pr

CH

2

4-Cl

O

140-141

1-50

CF

3

Pr-i

Me

CH

2

2-Me

O

154-155

1-51

CF

3

Pr-i

Me

CH

2

3-Me

O

93-94

1-52

CF

3

Pr-i

Me

CH

2

4-NO

3

O

146-149

1-53

CF

3

Bu-t

Me

CH

2

4-F

O

91-92

1-54

CF

3

Bu-t

Me

CH

2

4-Cl

O

111-112

1-55

CF

3

Bu-t

Me

CH

2

4-Me

O

84-87

1-56

CH

3

Pr-i

Me

CH

2

4-Cl

O

118-119

1-57

CF

3

Bu-s

Me

CH

2

H

O

70-71

1-58

CF

3

Bu-s

Me

CH

2

4-F

O

84-85

1-59

CF

3

Bu-s

Me

CH

2

4-Cl

O

73-75

1-60

CF

3

Bu-s

Me

CH

2

4-Me

O

61-64

1-61

CF

3

Pr-i

Et

CH

2

4-Me

O

92-94

1-62

CF

3

Pr-i

Pr

CH

2

4-Me

O

83-86

1-63

CF

3

Pr-i

Pr

CH

2

H

O

146-147

1-64

CF

3

Pr-i

Me

CH

2

O

H

O

117-119

1-65

CF

3

Pr-i

Me

CH

2

O

4-Cl

O

141-142

TABLE 3

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-66

CF

3

Pr-i

Me

CH

2

3-F

O

120-123

1-67

CF

3

Pr-i

Me

CH

2

4-Et

O

56-58

1-68

CF

3

Pr-i

Me

CH

2

4-Pr-i

O

86-87

1-69

Pr-i

Pr-i

Me

CH

2

S

H

O

1-70

CF

8

Pr-i

Me

CH

2

3-Br

O

120-121

1-71

CF

3

Pr-i

Me

CH(Me)

4-Cl

O

1.5232

1-72

CF

3

Pr-i

Me

CH

2

3,4-(Me)

2

O

83-85

1-73

Pr-i

Pr-i

Me

CH

2

S

4-Cl

O

1-74

CF

3

Pr-i

Me

CH

2

3-NO

2

O

118-121

1-75

CF

3

Pr-i

Me

CH

2

4-CN

O

141-142

1-76

CF

3

Pr-i

Me

CH

2

4-CH

2

OMe

O

58-60

1-77

CF

3

Pr-i

Me

CH

2

CH

2

H

O

79-82

1-78

Pr-c

Pr-i

Me

CH

2

4-Cl

O

110-113

1-79

Pr-i

Me

Me

CH

2

H

O

69-70

1-80

CF

3

Pr-i

Pr-c

CH

2

H

O

83-86

1-81

CF

3

Pr-i

Pr-c

CH

2

4-Cl

O

1.5297

1-82

CF

3

Pr-i

Pr-c

CH

2

4-Me

O

1.5218

1-83

CF

3

Pr-i

Pr-c

CH

2

4-F

O

81-84

1-84

CF

3

Pr-i

Me

CH

2

4-C≡CMe

O

128-132

1-85

CF

3

Pr-i

Me

CH═CH

H

O

1.5375

1-86

CF

3

Pr-i

Me

CH═CH

4-Cl

O

1.5565

1-87

Me

Pr-i

Me

CH

2

H

O

80-83

1-88

Me

Pr-i

Me

CH

2

4-F

O

102-104

1-89

Me

Pr-i

Me

CH

2

4-Me

O

106-107

1-90

H

Pr-i

Me

CH

2

4-Cl

O

1.5503

1-91

CClF

2

Pr-c

Me

CH

2

H

O

111-113

1-92

CClF

2

Pr-c

Me

CH

2

4-F

O

91-92

1-93

CClF

2

Pr-c

Me

CH

2

4-Me

O

87-88

1-94

CClF

2

Pr-c

Me

CH

2

4-Cl

O

112-114

1-95

CF

3

Pr-i

Me

CH

2

4-OCF

3

O

80-81

1-96

CF

3

Pr-i

Me

CH

2

4-OCHF

2

O

54-57

1-97

CF

3

Pr-i

Me

CH

2

4-OPr-i

O

74-75

1-98

CF

3

Pr-i

Et

CH

2

4-CN

O

139-142

1-99

CF

3

Pr-i

Pr

CH

2

4-CN

O

162-163

1-100

CF

3

Pr-i

Me

CH

2

2-F

O

163-164

1-101

Pr-c

Pr-i

Me

CH

2

4-F

O

111-112

TABLE 4

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-102

Pr-c

Pr-i

Me

CH

2

4-Me

O

81-83

1-103

CF

3

Pr-i

Pr-i

CH

2

H

O

1.5131

1-104

CF

3

Pr-i

Me

CH

2

4-SO

2

Me

O

137-139

1-105

CF

3

Pr-i

CH

2

OMe

CH

2

4-Cl

O

142-145

1-106

CF

3

Pr-i

CH

2

OMe

CH

2

4-Me

O

104-106

1-107

CF

3

Pr-i

CH

2

OEt

CH

2

4-Me

O

91-94

1-108

CF

3

Pr-i

Me

O

4-F

O

1-109

CF

3

Pr-i

Me

O

4-Me

O

1-110

CF

3

Pr-i

Me

O

4-Cl

O

1-111

CF

3

Pr

Me

CH

2

H

O

54-55

1-112

CF

3

Pr

Me

CH

2

4-F

O

67-70

1-113

CF

3

Pr

Me

CH

2

4-Me

O

63-64

1-114

CF

3

Pr

Me

CH

2

4-Cl

O

91-92

1-115

CF

3

Pr-i

Me

CH(Me)O

H

O

127-130

1-116

CF

3

Pr-i

Me

CH(Me)O

4-Cl

O

104-105

1-117

CF

3

Pr-i

Me

CH(Me)O

4-Me

O

1-118

CF

3

Pr-i

Me

OCH

2

H

O

1.5028

1-119

CF

3

Pr-i

Me

CH

2

S-OMe,4-Me

O

1.5109

1-120

CF

3

Pr-i

Me

CH

2

3-Me,4-Cl

O

92-94

1-121

CF

3

Pr-i

Me

CH

2

3-Cl,4-Me

O

121-122

1-122

CF

3

Pr-i

Me

CH

2

3,4-F

2

O

135-136

1-123

CF

3

Pr-i

Me

CH

2

2,6-F

2

O

176-177

1-124

CF

3

Pr-i

Me

CH

2

2,4-Cl

2

O

147-149

1-125

CF

3

Pr-i

Me

CH

2

O

2-F

O

157-158

1-126

CF

3

Pr-i

Me

CH

2

O

3-F

O

127-128

1-127

CF

3

Pr-i

Me

CH

2

O

4-F

O

119-121

1-128

Pr-i

Pr-i

Me

CH

2

H

O

118-119

1-129

Pr-i

Pr-i

Me

CH

2

4-F

O

125-126

1-130

Pr-i

Pr-i

Me

CH

2

4-Cl

O

123-126

1-131

Pr-i

Pr-i

Me

CH

2

4-Me

O

110-113

1-132

CF

3

Pr-i

Me

CH

2

O

2-Cl

O

162-163

1-133

CF

3

Pr-i

Me

CH

2

O

3-Cl

O

122-124

1-134

CF

3

Pr-i

Me

CH

2

O

2-Me

O

136-138

1-135

CF

3

Pr-i

Me

CH

2

O

3-Me

O

117-119

1-136

CF

3

Pr-i

Me

CH

2

O

4-Me

O

140-141

1-137

CF

3

Pen-c

Me

CH

2

H

O

72-74

TABLE 5

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-138

CF

3

Pen-c

Me

CH

2

4-F

O

97-99

1-139

CF

3

Pen-c

Me

CH

2

4-Cl

O

55-57

1-140

CF

3

Pen-c

Me

CH

2

4-Br

O

69-71

1-141

CF

3

Pen-c

Me

CH

2

4-Me

O

76-78

1-142

CF

3

Pr-i

Me

CH

2

H

S

93-94

1-143

CF

3

Pr-i

Me

CH

2

4-F

S

103-104

1-144

CF

3

Pr-i

Me

CH

2

4-Cl

S

92-93

1-145

CF

3

Pr-i

Me

CH

2

4-Me

S

1.5541

1-146

CF

3

Pr-i

Me

CH

2

3,4-(-OCH

2

O-)

O

82-85

1-147

CF

3

Pr-i

Me

CH

2

2,4-F

2

O

137-139

1-148

CF

3

Pr-i

Me

CH

2

2,3-F

2

O

183-184

1-149

CF

3

Pr-i

Me

CH

2

2,3,4-F

3

O

1-150

SMe

Pr-i

Me

CH

2

H

O

88-89

1-151

SMe

Pr-i

Me

CH

2

4-Cl

O

125-127

1-152

SMe

Pr-i

Me

CH

2

4-F

O

121-124

1-153

SMe

Pr-i

Me

CH

2

4-Me

O

78-79

1-154

CF

3

Pr-i

Me

CH(SMe)

4-Cl

O

148-149

1-155

CF

3

Pr-i

Me

CH(OMe)

4-Cl

O

107-108

1-156

CF

3

Pen-c

Me

CH

2

2-F

O

111-112

1-157

CF

3

Pr-i

Me

CH

2

4-N(Me)

2

O

109-111

1-158

CF

3

Ph(4-F)

Me

CH

2

3-F

O

85-86

1-159

CH

3

Bu-t

Me

CH

2

H

O

93-95

1-160

CH

3

Bu-t

Me

CH

2

4-F

O

96-98

1-161

CH

3

Bu-t

Me

CH

2

4-Cl

O

107-109

1-162

CH

3

Bu-t

Me

CH

2

4-Me

O

84-86

1-163

CHF

2

Pr-i

Me

CH

2

H

O

62-65

1-164

CHF

2

Pr-i

Me

CH

2

4-F

O

82-84

1-165

CHF

2

Pr-i

Me

CH

2

4-Cl

O

85-87

1-166

CHF

2

Pr-i

Me

CH

2

4-Me

O

83-84

1-167

CF

3

Pr-i

Me

CH

2

3,5-F

2

O

156-157

1-168

CHF

2

Pr-i

Et

CH

2

H

O

85-86

1-169

CHF

2

Pr-i

Et

CH

2

4-F

O

100-103

1-170

CHF

2

Pr-i

Et

CH

2

4-Cl

O

114-117

1-171

CHF

2

Pr-i

Et

CH

2

4-Me

O

91-92

1-172

CF

3

Pr-i

CH

2

C≡CH

CH

2

4-F

O

124-128

TABLE 6

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-173

CF

3

Pr-i

Et

CH

2

3-F

O

119-121

1-174

CF

3

Pr-i

Et

CH

2

4-CF

3

O

100-101

1-175

CF

3

Pr-i

Me

C(Me)

2

4-Me

O

108-110

1-176

CF

3

Pr-i

Me

O

H

O

80-81

1-177

CF

3

Pr-i

Me

O

4-F

O

110-112

1-178

CF

3

Pr-i

Me

O

4-Cl

O

112-115

1-179

CF

3

Pr-i

Me

O

4-Me

O

94-97

1-180

CF

3

Pr-i

Me

CH

2

3-F,4-Cl

O

120-124

1-181

CF

3

Pr-i

Pr

CH

2

4-F

O

126-127

1-182

CF

3

Pr-i

Me

CH

2

S

H

O

106-108

1-183

CF

3

Pr-i

Me

CH

2

S

4-Cl

O

111-113

1-184

CClF

2

Pr-i

Me

O

4-F

O

119-123

1-185

CClF

2

Pr-i

Me

O

4-Cl

O

99-103

1-186

CF

3

Ph

Me

CH

2

H

O

86-87

1-187

CF

3

Ph

Me

CH

2

4-Cl

O

146-147

1-188

Bu-t

Me

Me

CH

2

H

O

1.5511

1-189

Bu-t

Me

Me

CH

2

4-F

O

88-89

1-190

Bu-t

Me

Me

CH

2

4-Cl

O

1.5582

1-191

Bu-t

Me

Me

CH

2

4-Me

O

1.5471

1-192

CF

3

Pr-i

Me

CH(Me)

4-OMe

O

1.5135

1-193

CF

3

Pr-i

CH

2

C≡CH

CH

2

H

O

117-121

1-194

CF

3

Pr-i

CH

2

C≡CH

CH

2

4-Cl

O

119-121

1-195

CF

3

Pr-i

Me

CH(Me)

H

O

Not Measurable

1-196

CF

3

Bu-t

Me

CH

2

H

O

107-109

1-197

CF

3

Ph

Me

CH

2

4-Me

O

151-154

1-198

CF

3

Pr-i

Me

CH(Me)

4-F

O

1.4992

1-199

CF

3

Pr-i

Me

CH(Me)

4-Me

O

1-200

CF

3

2-thienyl

Me

CH

2

4-Cl

O

120-121

1-201

SMe

Bu-t

Me

CH

2

H

O

1-202

SMe

Bu-t

Me

CH

2

4-F

O

1-203

SMe

Bu-t

Me

CH

2

4-Cl

O

1-204

SMe

Bu-t

Me

CH

2

4-Me

O

1-205

SMe

Ph

Me

CH

2

H

O

1-206

SMe

Ph

Me

CH

2

4-F

O

1-207

SMe

Ph

Me

CH

2

4-Cl

O

1-208

SMe

Ph

Me

CH

2

4-Me

O

TABLE 7

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-209

Pr-i

Bu-t

Me

CH

2

H

O

1-210

Pr-i

Bu-t

Me

CH

2

4-F

o

1-211

Pr-i

Bu-t

Me

CH

2

4-Cl

O

1-212

Pr-i

Bu-t

Me

CH

2

4-Me

O

1-213

Pr-i

Ph

Me

CH

2

H

O

1-214

Pr-i

Ph

Me

CH

2

4-F

O

90-91

1-215

Pr-i

Ph

Me

CH

2

4-Cl

O

1-216

Pr-i

Ph

Me

CH

2

4-Me

O

1-217

CF

3

Ph(4-F)

Me

CH

2

H

O

111-112

1-218

CF

3

Ph(4-F)

Me

CH

2

4-F

O

99-101

1-219

CF

3

Ph(4-F)

Me

CH

2

4-Cl

O

137-139

1-220

CF

3

Ph(4-F)

Me

CH

2

4-Me

O

132-134

1-221

CF

3

Ph(4-Cl)

Me

CH

2

H

O

136-137

1-222

CF

3

Ph(4-Cl)

Me

CH

2

4-F

O

114-115

1-223

CF

3

Ph(4-Cl)

Me

CH

2

4-Cl

O

1-224

CF

3

Ph(4-Cl)

Me

CH

2

4-Me

O

1-225

CF

3

Ph(4-Me)

Me

CH

2

H

O

1.5566

1-226

CF

3

Ph(4-Me)

Me

CH

2

4-F

O

1.5549

1-227

CF

3

Ph(4-Me)

Me

CH

2

4-Cl

O

1-228

CF

3

Ph(4-Me)

Me

CH

2

4-Me

O

1.5531

1-229

CF

3

3-thienyl

Me

CH

2

H

O

1-230

CF

3

3-thienyl

Me

CH

2

4-F

O

1-231

CF

3

3-thienyl

Me

CH

2

4-Cl

O

1-232

CF

3

3-thienyl

Me

CH

2

4-Me

O

1-233

CF

3

2-thienyl

Me

CH

2

H

O

1-234

CF

3

2-thienyl

Me

CH

2

4-F

O

99-103

1-235

CF

3

2-thienyl

Me

CH

2

4-Cl

O

1-236

CF

3

2-thienyl

Me

CH

2

4-Me

O

1-237

CF

3

Ph(3-Cl)

Me

CH

2

H

O

1-238

CF

3

Ph(3-Cl)

Me

CH

2

4-F

O

1-239

CF

3

Ph(3-Cl)

Me

CH

2

4-Cl

O

1-240

CF

3

Ph(3-Cl)

Me

CH

2

4-Me

O

1-241

CF

3

Bu-t

Me

CH

2

4-Br

O

1-242

CF

3

Ph

Me

CH

2

4-Br

O

1-243

CF

3

Bu-s

Me

CH

2

4-Br

O

1-244

CHF

2

Pr-i

Me

CH

2

4-Br

O

TABLE 8

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-245

SMe

Pr-i

Me

CH

2

4-Br

O

1-246

Pr-i

Pr-i

Me

CH

2

4-Br

O

1-247

Pr-c

Pr-i

Me

CH

2

4-Br

O

1-248

Me

Bu-t

Me

CH

2

4-Br

O

1-249

CF

3

Bu-t

Me

CH

2

2-F,4-Cl

O

101-103

1-250

CF

3

Ph

Me

CH

2

2-F,4-Cl

O

170—173

1-251

CF

3

Bu-s

Me

CH

2

2-F,4-Cl

O

84-85

1-252

CHF

2

Pr-i

Me

CH

2

2-F,4-Cl

O

1-253

SMe

Pr-i

Me

CH

2

2-F,4-Cl

O

1-254

Pr-i

Pr-i

Me

CH

2

2-F,4-Cl

O

141-142

1-255

Pr-c

Pr-i

Me

CH

2

2-F,4-Cl

O

1-256

Me

Bu-t

Me

CH

2

2-F,4-Cl

O

1-257

CF

3

Bu-t

Me

CH

2

3,4-(Me)

2

O

1-258

CF

3

Ph

Me

CH

2

3,4-(Me)

2

O

1-259

CF

3

Bu-s

Me

CH

2

3,4-(Me)

2

O

1-260

CHF

2

Pr-i

Me

CH

2

3,4-(Me)

2

O

1-261

SMe

Pr-i

Me

CH

2

3,4-(Me)

2

O

1-262

Pr-i

Pr-i

Me

CH

2

3,4-(Me)

2

O

1-263

Pr-i

Pr-c

Me

CH

2

3,4-(Me)

2

O

1-264

Me

Bu-t

Me

CH

2

3,4-(Me)

2

O

1-265

CF

3

Bu-t

Me

CH

2

3-F

O

103-104

1-266

CF

3

Ph

Me

CH

2

3-F

O

88-90

1-267

CF

3

Bu-s

Me

CH

2

3-F

O

85-87

1-268

CHF

3

Pr-i

Me

CH

2

3-F

O

1-269

SMe

Pr-i

Me

CH

2

3-F

O

1-270

Pr-i

Pr-i

Me

CH

2

3-F

O

151-153

1-271

Pr-c

Pr-i

Me

CH

2

3-F

O

1-272

Me

Bu-t

Me

CH

2

3-F

O

1-273

CF

3

Bu-t

Me

CH

2

2,4-F

2

O

137-140

1-274

CF

3

Ph

Me

CH

2

2,4-F

2

O

107-110

1-275

CF

3

Bu-s

Me

CH

2

2,4-F

2

O

1-276

CHF

2

Pr-i

Me

CH

2

2,4-F

2

O

1-277

SMe

Pr-i

Me

CH

2

2,4-F

2

O

1-278

Pr-i

Pr-i

Me

CH

2

2,4-F

2

O

1-279

Pr-c

Pr-i

Me

CH

2

2,4-F

2

O

1-280

Me

Bu-t

Me

CH

2

2,4-F

2

O

TABLE 9

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-281

CF

3

Bu-t

Me

CH

2

3-F,4-Cl

O

1-282

CF

3

Ph

Me

CH

2

3-F,4-Cl

O

1-283

CF

3

Bu-s

Me

CH

2

3-F,4-Cl

O

1-284

CHF

2

Pr-i

Me

CH

2

3-F,4-Cl

O

1-285

SMe

Pr-i

Me

CH

2

3-F,4-Cl

O

1-286

Pr-i

Pr-i

Me

CH

2

3-F,4-Cl

O

1-287

Pr-c

Pr-i

Me

CH

2

3-F,4-Cl

O

1-288

Me

Bu-t

Me

CH

2

3-F,4-Cl

O

1-289

CF

3

Bu-t

Me

CH

2

3,4-F

3

O

1-290

CF

3

Ph

Me

CH

2

3,4-F

3

O

1-291

CF

3

Bu-s

Me

CH

2

3,4-F

3

O

1-292

CHF

2

Pr-i

Me

CH

2

3,4-F

3

O

1-293

SMe

Pr-i

Me

CH

2

3,4-F

3

O

1-294

Pr-i

Pr-i

Me

CH

2

3,4-F

3

O

1-295

Pr-c

Pr-i

Me

CH

2

3,4-F

3

O

1-296

Me

Bu-t

Me

CH

2

3,4-F

3

O

1-297

CF

3

Bu-t

Me

CH

2

3,5-F

3

O

1-298

CF

3

Ph

Me

CH

2

3,5-F

3

O

1-299

CF

3

Bu-s

Me

CH

2

3,5-F

3

O

1-300

CHF

2

Pr-i

Me

CH

2

3,5-F

3

O

1-301

SMe

Pr-i

Me

CH

2

3,5-F

3

O

1-302

Pr-i

Pr-i

Me

CH

2

3,5-F

3

O

1-303

Pr-c

Pr-i

Me

CH

2

3,5-F

3

O

1-304

Me

Bu-t

Me

CH

2

3,5-F

3

O

1-305

CF

3

Bu-t

Me

CH

2

4-CF

3

O

85-87

1-306

CF

3

Ph

Me

CH

2

4-CF

3

O

92-93

1-307

CF

3

Bu-s

Me

CH

2

4-CF

3

O

123-125

1-308

CHF

2

Pr-i

Me

CH

2

4-CF

3

O

1-309

SMe

Pr-i

Me

CH

2

4-CF

3

O

1-310

Pr-i

Pr-i

Me

CH

2

4-CF

3

O

139-140

1-311

Pr-c

Pr-i

Me

CH

2

4-CF

3

O

1-312

Me

Bu-t

Me

CH

2

4-CF

3

O

1-313

CF

3

Bu-t

Me

CH

2

3-CF

3

O

1-314

CF

3

Ph

Me

CH

2

3-CF

3

O

1-315

CF

3

Bu-s

Me

CH

2

3-CF

3

O

1-316

CHF

2

Pr-i

Me

CH

2

3-CF

3

O

TABLE 10

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-317

SMe

Pr-i

Me

CH

2

3-CF

3

O

1-318

Pr-i

Pr-i

Me

CH

2

3-CF

3

O

1-319

Pr-c

Pr-i

Me

CH

2

3-CF

3

O

1-320

Me

Bu-t

Me

CH

2

3-CF

3

O

1-321

CF

3

Pr-i

Et

CH

2

2-F,4-Cl

O

144-146

1-322

Ph

Pr-i

Me

CH

2

H

O

82-84

1-323

Ph

Pr-i

Me

CH

2

4-F

O

104-105

1-324

Ph

Pr-i

Me

CH

2

4-Cl

O

88-90

1-325

Ph

Pr-i

Me

CH

2

4-Me

O

79-80

1-326

Pr-i

Pr-i

Me

NH

H

O

199-200

1-327

Pr-i

Pr-i

Me

N(Me)

H

O

1.5384

1-328

CF

3

Pr-i

Me

C(═O)

H

O

101-102

1-329

CF

3

Pr-i

Me

C(Me)

2

4-Cl

O

Not Measurable

1-330

CF

3

Bu-i

Me

CH

2

H

O

86-87

1-331

CF

3

Bu-i

Me

CH

2

4-F

O

97-98

1-332

CF

3

Pr-i

OMe

CH

2

H

O

1.5071

1-333

CF

3

Pr-i

OMe

CH

2

4-F

O

59-62

1-334

CF

3

Bu-i

Me

CH

2

3-F

O

93-94

1-335

CF

3

Pr-i

Me

C(═O)

4-Cl

O

116-119

1-336

Pr-i

Ph

Et

CH

2

4-Me

O

1-337

CF

3

Ph(4-F)

Et

CH

2

H

O

1-338

CF

3

Ph(4-F)

Et

CH

2

4-F

O

1-339

CF

3

Ph(4-F)

Et

CH

2

4-Cl

O

1-340

CF

3

Ph(4-F)

Et

CH

2

4-Me

O

1-341

CF

3

Ph(4-Cl)

Et

CH

2

H

O

1-342

CF

3

Ph(4-Cl)

Et

CH

2

4-F

O

1-343

CF

3

Ph(4-Cl)

Et

CH

2

4-Cl

O

1-344

CF

3

Ph(4-Cl)

Et

CH

2

4-Me

O

1-345

CF

3

Ph(4-Me)

Et

CH

2

H

O

1-346

CF

3

Ph(4-Me)

Et

CH

2

4-F

O

1-347

CF

3

Ph(4-Me)

Et

CH

2

4-Cl

O

1-348

CF

3

Ph(4-Me)

Et

CH

2

4-Me

O

1-349

CF

3

3-thienyl

Et

CH

2

H

O

1-350

CF

3

3-thienyl

Et

CH

2

4-F

O

1-351

CF

3

3-thienyl

Et

CH

2

4-Cl

O

1-352

CF

3

3-thienyl

Et

CH

2

4-Me

O

TABLE 11

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-353

CF

3

2-thienyl

Et

CH

2

H

O

1-354

CF

3

2-thienyl

Et

CH

2

4-F

O

1-355

CF

3

2-thienyl

Et

CH

2

4-Cl

O

1-356

CF

3

2-thienyl

Et

CH

2

4-Me

O

1-357

CF

3

Ph(3-Cl)

Et

CH

2

H

O

1-358

CF

3

Ph(3-Cl)

Et

CH

2

4-F

O

1-359

CF

3

Ph(3-Cl)

Et

CH

2

4-Cl

O

1-360

CF

3

Ph(3-Cl)

Et

CH

2

4-Me

O

1-361

CF

3

Ph

Me

CH(Me)

H

O

1-362

CF

3

Ph

Me

CH(Me)

4-F

O

1-363

CF

3

Ph

Me

CH(Me)

4-Cl

O

1-364

CF

3

Ph

Me

CH(Me)

4-Me

O

1-365

CF

3

Ph(4-F)

Me

CH(Me)

H

O

1-366

CF

3

Ph(4-F)

Me

CH(Me)

4-F

O

1-367

CF

3

Ph(4-F)

Me

CH(Me)

4-Cl

O

1-368

CF

3

Ph(4-F)

Me

CH(Me)

4-Me

O

1-369

CF

3

Ph(4-Cl)

Me

CH(Me)

H

O

1-370

CF

3

Ph(4-Cl)

Me

CH(Me)

4-F

O

1-371

CF

3

Ph(4-Cl)

Me

CH(Me)

4-Cl

O

1-372

CF

3

Ph(4-Cl)

Me

CH(Me)

4-Me

O

1-373

Pr-i

Pr-i

Me

CH(Me)

H

O

1-374

Pr-i

Pr-i

Me

CH(Me)

4-F

O

1-375

Pr-i

Pr-i

Me

CH(Me)

4-Cl

O

1-376

Pr-i

Pr-i

Me

CH(Me)

4-Me

O

1-377

SMe

Pr-i

Me

CH(Me)

H

O

1-378

SMe

Pr-i

Me

CH(Me)

4-F

O

1-379

SMe

Pr-i

Me

CH(Me)

4-Cl

O

1-380

SMe

Pr-i

Me

CH(Me)

4-Me

O

1-381

CF

3

3-thienyl

Me

CH(Me)

H

O

1-382

CF

3

3-thienyl

Me

CH(Me)

4-F

O

1-383

CF

3

3-thienyl

Me

CH(Me)

4-Cl

O

1-384

CF

3

3-thienyl

Me

CH(Me)

4-Me

O

1-385

CF

3

Ph(3-Cl)

Me

CH(Me)

H

O

1-386

CF

3

Ph(3-Cl)

Me

CH(Me)

4-F

O

1-387

CF

3

Ph(3-Cl)

Me

CH(Me)

4-Cl

O

1-388

CF

3

Ph(3-Cl)

Me

CH(Me)

4-Me

O

1-389

Me

Bu-t

Me

CH(Me)

H

O

TABLE 12

m.p.

(° C.) or

refrac-

Dia-

tive

Compound

stereo-

index

No.

R

1

R

2

R

3

Z

Xn

Q

mer

(n

D

20

)

1-390

Me

Bu-t

Me

CH(Me)

4-F

O

1-391

Me

Bu-t

Me

CH(Me)

4-Cl

O

1-392

Me

Bu-t

Me

CH(Me)

4-Me

O

1-393

CF

3

Bu-t

Me

CH(Me)

H

O

1-394

CF

3

Bu-t

Me

CH(Me)

4-F

O

1-395

CF

3

Bu-t

Me

CH(Me)

4-Cl

O

1-396

CF

3

Bu-t

Me

CH(Me)

4-Me

O

1-397

CF

3

2-thienyl

Me

CH(Me)

H

O

1-398

CF

3

2-thienyl

Me

CH(Me)

4-F

O

1-399

CF

3

2-thienyl

Me

CH(Me)

4-Cl

O

1-400

CF

3

2-thienyl

Me

CH(Me)

4-Me

O

1-401

OMe

Pr-i

Me

CH

2

H

O

1.5439

1-402

OMe

Pr-i

Me

CH

2

4-F

O

1.5332

1-403

OMe

Pr-i

Me

CH

2

4-Cl

O

79-82

1-404

OMe

Pr-i

Me

CH

2

4-Me

O

88-90

1-405

CF

3

Pr-i

OMe

CH

2

H

O

1-406

CF

3

Pr-i

OMe

CH

2

4-F

O

1-407

CF

3

Pr-i

OMe

CH

2

4-Cl

O

1.5159

1-408

CF

3

Pr-i

OMe

CH

2

4-Me

O

1-409

CF

3

1-MePr-e

Me

CH

2

H

O

78-79

1-410

CF

3

Me

CH

2

4-F

O

85-87

1-411

CF

3

Me

CH

2

4-Cl

O

110-111

1-412

CF

3

Me

CH

2

4-Me

O

88-89

1-413

CF

3

CH

2

SMe

Me

CH

2

4-F

O

65-66

1-414

CF

3

CH

2

SMe

Me

CH

2

4-Cl

O

94-95

1-415

CF

3

CH

2

SMe

Me

CH

2

4-Br

O

109-110

1-416

CF

3

CH(Me)SMe

Me

CH

2

4-F

O

118-119

1-417

CF

3

Pr-i

Me

CH

2

2,3,4-F

3

O

167-169

1-418

CF

3

Pr-i

Me

CH

2

3,4,5-F

3

O

181-183

1-419

CF

3

1-MePr-e

Me

CH

2

3-F

O

100-101

1-420

CF

3

CH

2

SMe

Me

CH

2

3-F

O

66-67

1-421

CF

3

CH

2

SMe

Me

CH

2

4-Me

O

87-89

1-422

CF

3

CH

2

SMe

Me

CH

2

2-F-

O

102-103

4-Cl

TABLE 13

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-423

CF

3

Et

Pr-i

CH

2

4-Cl

O

1.5207

1-424

CF

3

Pr-i

Me

N-Me

H

O

104-105

1-425

CF

3

Pr-i

Me

N-Et

H

O

63-65

1-426

CF

3

Pr-i

Me

N-Me

4-F

O

84-85

1-427

CF

3

Pr-i

Me

N-Me

4-Cl

O

106-108

1-428

CF

3

Pr-i

Me

N-Me

4-Me

O

94-96

1-429

Pr-i

Pr-i

Me

N-Me

4-F

O

1.5216

1-430

Pr-i

Pr-i

Me

N-Me

4-Cl

O

120-123

1-431

Pr-i

Pr-i

Me

N-Me

4-Me

O

93-94

1-432

Et

Pr-i

Me

CH

2

H

O

97-98

1-433

Et

Pr-i

Me

CH

2

4-F

O

93-95

1-434

Et

Pr-i

Me

CH

2

4-Cl

O

110-111

1-435

Et

Pr-i

Me

CH

2

4-Me

O

79-81

1-436

Pr-i

Et

Me

CH

2

H

O

1.5455

1-437

Pr-i

Et

Me

CH

2

4-F

O

66-67

1-438

Pr-i

Et

Me

CH

2

4-Cl

O

110-111

1-439

Pr-i

Et

Me

CH

2

4-Me

O

98-99

1-440

CF

3

3-thienyl

Me

CH

2

H

O

1-441

CF

3

3-thienyl

Me

CH

2

4-F

O

109-110

1-442

CF

3

3-thienyl

Me

CH

2

4-Cl

O

135-138

1-443

CF

3

3-thienyl

Me

CH

2

4-Me

O

125-128

1-444

CF

3

Pr-i

Me

CH

2

2,3,5-F

3

O

167-169

1-445

Pr-n

Pr-i

Me

CH

2

H

O

67-69

1-446

Pr-n

Pr-i

Me

CH

2

4-F

O

117-118

1-447

Pr-n

Pr-i

Me

CH

2

4-Cl

O

122-123

1-448

Pr-n

Pr-i

Me

CH

2

4-Me

O

89-90

1-449

Pr-i

Pr-n

Me

CH

2

H

O

1.5402

1-450

Pr-i

Pr-n

Me

CH

2

4-F

O

83-84

1-451

Pr-i

Pr-n

Me

CH

2

4-Cl

O

78-79

1-452

Pr-i

Pr-n

Me

CH

2

4-Me

O

94-95

1-453

CH(OEt)

2

Pr-i

Me

CH

2

H

O

1.5253

1-454

Pr-i

CH(OEt)

2

Me

CH

2

H

O

1.5221

1-455

Pr-i

CH(OEt)

2

Me

CH

2

4-F

O

1.5101

1-456

Pr-i

CH(OEt)

2

Me

CH

2

4-Cl

O

1-457

Pr-i

CH(OEt)

2

Me

CH

2

4-Me

O

1-458

Pr-i

CH(OEt)

2

Me

OCH

2

H

O

1.5191

TABLE 14

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Xn

Q

Diastereomer

(n

D

20

)

1-459

CF

3

Pr-i

Me

N-Me

4-CN

O

144-145

1-460

CF

3

Pr-i

Me

N-Me

4-OMe

O

1.5081

1-461

CF

3

Pr-i

Me

NHCH

2

H

O

92-95

1-462

Pr-i

CH═NOMe

Me

CH

2

H

O

1-463

Pr-i

CH═NOMe

Me

CH

2

4-F

O

1.5309

1-464

Pr-i

CH═NOMe

Me

CH

2

4-Cl

O

1.5459

1-465

Pr-i

CH═NOMe

Me

CH

2

4-Me

O

1.5412

1-466

Pr-i

CH═NOMe

Me

OCH

2

H

O

1.5352

1-467

CH(OEt)

2

Pr-i

Me

OCH

2

H

O

1.5236

1-468

CH(OEt)

2

Pr-i

Me

CH

2

4-F

O

1.5135

1-469

CH(OEt)

2

Pr-i

Me

CH

2

4-Cl

O

1.5282

1-470

CH(OEt)

2

Pr-i

Me

CH

2

4-Me

O

116-117

1-471

CH═NOMe

Pr-i

Me

OCH

2

H

O

1.5481

1-472

Me

CH

2

H

O

1-473

Me

CH

2

4-F

O

110-112

1-474

Me

CH

2

4-Cl

O

1-475

CH

2

CO

2

Et

CH

2

4-Me

O

1-476

CF

3

Pr-i

CH

2

CO

2

Et

CH

2

H

O

158-159

1-477

CF

3

Pr-i

CH

2

CO

2

Et

CH

2

4-F

O

1-478

CF

3

Pr-i

CH

2

CO

2

Et

CH

2

4-Cl

O

1-479

CF

3

Pr-i

CH

2

CO

2

Et

CH

2

4-Me

O

1-480

CF

3

Pr-i

CH

2

CN

CH

2

H

O

1-481

CF

3

Pr-i

CH

2

CN

CH

2

4-F

O

1-482

CF

3

Pr-i

CH

2

CN

CH

2

4-Cl

O

164-166

1-483

CF

3

Pr-i

CH

2

CN

CH

2

4-Me

O

159-161

1-484

CF

3

Ph(4-OMe)

Me

CH

2

H

O

97-98

1-485

CF

3

Ph(4-OMe)

Me

CH

2

4-F

O

103-105

1-486

CF

3

Ph(4-OMe)

Me

CH

2

4-Cl

O

131-133

1-487

CF

3

Ph(4-OMe)

Me

CH

2

4-Me

O

147-150

1-488

CF

3

Ph(2-OMe)

Me

CH

2

H

O

Not

Measurable

TABLE 15

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-489

CF

3

Ph(2-OMe)

Me

CH

2

4-F

O

1.5474

1-490

CF

3

Ph(2-OMe)

Me

CH

2

4-Cl

O

Not Measurable

1-491

CF

3

Ph(2-OMe)

Me

CH

2

4-Me

O

1.5432

1-492

Pr-n

Pr-n

Me

CH

2

H

O

65-66

1-493

Pr-n

Pr-n

Me

CH

2

4-F

O

83-84

1-494

Pr-n

Pr-n

Me

CH

2

4-Cl

O

91-92

1-495

Pr-n

Pr-n

Me

CH

2

4-Me

O

55‥56

1-496

CH═NOMe

Pr-i

Me

CH

2

H

O

113-115

1-497

CH═NOMe

Pr-i

Me

CH

2

4-F

O

155-156

1-498

CH═NOMe

Pr-i

Me

CH

2

4-Cl

O

122-123

1-499

CH═NOMe

Pr-i

Me

CH

2

4-Me

O

1.5468

1-500

CH═NOH

Pr-i

Me

CH

2

H

O

171-172

1-501

CH═NOH

Pr-i

Me

CH

2

4-F

O

197-198

1-502

CH═NOH

Pr-i

Me

CH

2

4-Cl

O

183-184

1-503

CH═NOH

Pr-i

Me

CH

2

4-Me

O

155-157

1-504

CN

Pr-i

Me

CH

2

H

O

80-81

1-505

CN

Pr-i

Me

CH

2

4-F

O

105-106

1-506

CN

Pr-i

Me

CH

2

4-Cl

O

99-100

1-507

CN

Pr-i

Me

CH

2

4-Me

O

75-76

1-508

CN

Pr-i

Me

CH(Me)

4-Cl

O

1.6669

1-509

Pr-i

CMe(OMe)

2

Me

CH

2

H

O

1.5352

1-510

Pr-i

CMe(OMe)

2

Me

CH

2

4-F

O

112-113

1-511

Pr-i

CMe(OMe)

2

Me

CH

2

4-Cl

O

106-107

1-512

Pr-i

CMe(OMe)

2

Me

CH

2

4-Me

O

104-105

1-513

Pr-i

COMe

Me

CH

2

H

O

99-100

1-514

Pr-i

COMe

Me

CH

2

4-F

O

114-115

1-515

Pr-i

COMe

Me

CH

2

4-Cl

O

108-109

1-516

Pr-i

COMe

Me

CH

2

4-Me

O

119-120

1-517

CMe(OMe)

2

Pr-i

Me

CH

2

4-Cl

O

78-79

1-518

CF

3

Pr-i

CH

2

CH═CH

2

CH

2

H

O

121-122

1-519

CF

3

Pr-i

CH

2

CH═CH

2

CH

2

4-F

O

129-130

1-520

CF

3

Pr-i

CH

2

CH═CH

2

CH

2

4-Cl

O

124-127

1-521

CF

3

Pr-i

CH

2

CH═CH

2

CH

2

4-Me

O

98-99

1-522

CHO

Pr-i

Me

CH

2

H

O

1-523

CHO

Pr-i

Me

CH

2

4-F

O

1.5466

1-524

CHO

Pr-i

Me

CH

2

4-Cl

O

1.5609

TABLE 16

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Xn

Q

Diastereomer

(n

D

20

)

1-525

CHO

Pr-i

Me

CH

2

4-Me

O

1.5558

1-526

COMe

Pr-i

Me

CH

2

H

O

Not

Measurable

1-527

COMe

Pr-i

Me

CH

2

4-F

O

1.5341

1-528

COMe

Pr-i

Me

CH

2

4-Cl

O

1.5501

1-529

COMe

Pr-i

Me

CH

2

4-Me

O

1.5423

1-530

COMe

Pr-i

Me

CH(Me)

4-Cl

O

1.5395

1-531

Pr-i

CH═NOH

Me

OCH

2

H

O

1.5365

1-532

CF

3

Pr-i

Me

N(Me)CH

2

4-Cl

O

95-96

1-533

CF

3

Pr-i

Me

N(CH

2

C≡CH)

4-F

O

1.5121

1-534

CF

3

Pr-i

Me

NHCH(Me)

H

O

69-70

(R-isomer)

1-535

CF

3

Pr-i

Me

NHCH(Me)

H

O

1.5134

(S-isomer)

1-536

CF

3

Pr-i

Me

N(Me)

2-F

O

1.5043

1-537

CF

3

Pr-i

Me

N(Me)

2,4-F

2

O

1.4936

1-538

Et

Pr-i

Me

N(Me)

H

O

1.5451

1-539

Et

Pr-i

Me

N(Me)

4-F

O

1.5349

1-540

Et

Pr-i

Me

N(Me)

4-Cl

O

115-117

1-541

Et

Pr-i

Me

N(Me)

4-Me

O

1.5342

1-542

CF

3

Pr-i

CH

2

H

O

1.5131

1-543

CF

3

Pr-i

CH

2

4-F

O

1.5052

1-544

CF

3

Pr-i

CH

2

4-Cl

O

1.5215

1-545

CF

3

Pr-i

CH

2

4-Me

O

1.5121

1-546

CF

3

Ph(2-F)

Me

CH

2

H

O

109-110

1-547

CF

3

Ph(2-F)

Me

CH

2

4-F

O

107-108

1-548

CF

3

Ph(2-F)

Me

CH

2

4-Cl

O

139-141

1-549

CF

3

Ph(2-F)

Me

CH

2

4-Me

O

107-110

1-550

CF

3

Ph(2-Me)

Me

CH

2

H

O

146-147

1-551

CF

3

Ph(2-Me)

Me

CH

2

4-F

O

149-150

1-552

CF

3

Ph(2-Me)

Me

CH

2

4-Cl

1-553

CF

3

Ph(2-Me)

Me

CH

2

4-Me

O

135-136

TABLE 17

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1.554

CF

3

Ph(2,4-F

2

)

Me

CH

2

H

O

1.555

CF

3

Ph(2,4-F

2

)

Me

CH

2

4-F

O

102-104

1-556

CF

3

Ph(2,4-F

2

)

Me

CH

2

4-Cl

O

1-557

CF

3

Ph(2,4-F

2

)

Me

CH

2

4-Me

O

1-558

Et

Pr-i

CH

2

C≡CH

CH

2

H

O

131-132

1-559

Et

Pr-i

CH

2

C≡CH

CH

2

4-F

O

93-96

1-560

Et

Pr-i

CH

2

C≡CH

CH

2

4-Cl

O

124-125

1-561

Et

Pr-i

CH

2

C≡CH

CH

2

4-Me

O

110-111

1-562

Et

Pr-i

CH

2

C≡CH

CH(Me)

H

O

Not Measurable

1-563

Pr-i

C(Me)═NOMe

Me

CH

2

4-F

O

73-74

1-564

Et

Bu-t

Mo

CH

2

H

O

1-565

Et

Bu-t

Me

CH

2

4-F

O

82-83

1-566

Et

Bu-t

Me

CH

2

4-Cl

O

98-99

1-567

Et

Bu-t

Me

CH

2

4-Me

O

78-80

1-568

Pr-i

CN

Me

OCH

2

H

O

1.5899

1-569

CF

3

Pr-i

CH

2

C≡CH

CH

2

3-F

O

131-133

1-570

Bu-t

Et

Me

CH

2

H

O

1-571

Bu-t

Et

Me

CH

2

4-F

O

88-90

1-572

Bu-t

Et

Me

CH

2

4-Cl

O

96-97

1-573

Bu-t

Et

Me

CH

2

4-Me

O

101-102

1-574

CF

3

Pr-i

CH

2

-Pr-c

CH

2

H

O

1-575

CF

3

Pr-i

CH

2

-Pr-c

CH

2

4-F

O

108-109

1-576

CF

3

Pr-i

CH

2

-Pr-c

CH

2

4-Cl

O

1-577

CF

3

Pr-i

CH

2

-Pr-c

CH

2

4-Me

O

1-578

CF

3

Pr-i

CH

2

CN

CH

2

H

O

1-579

CF

3

Pr-i

CH

2

CN

CH

2

4-F

O

162-163

1-580

CF

3

Pr-i

CH

2

CN

CH

2

4-Cl

O

1-581

CF

3

Pr-i

CH

2

CN

CH

2

4-Me

O

1-582

Pr-i

CH

2

OMe

Me

CH

2

H

O

1-583

Pr-i

CH

2

OMe

Me

CH

2

4-F

O

1-584

Pr-i

CH

2

OMe

Me

CH

2

4-Cl

O

1.5391

1-585

Pr-i

CH

2

OMe

Me

CH

2

4-Me

O

1-586

Pr-i

CH

2

OMe

Me

CH(Me)

4-Cl

O

1.5358

1-587

CH

2

OMe

Pr-i

Me

CH

2

H

O

1-588

CH

2

OMe

Pr-i

Me

CH

2

4-F

O

1-589

CH

2

OMe

Pr-i

Me

CH

2

4-Cl

O

1.5485

TABLE 18

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Xn

Q

Diastereomer

(n

D

20

)

1-590

CH

2

OMe

Pr-i

Me

CH

2

4-Me

O

1-591

CH

2

OMe

Pr-i

Me

CH(Me)

4-Cl

O

1.5382

1-592

CO

2

Me

Pr-i

Me

CH(Me)

4-Cl

O

A-isomer

Not

Measurable

1-593

CO

2

Me

Pr-i

Me

CH(Me)

4-Cl

O

B-isomer

Not

Measurable

1-594

CO

2

Et

Pr-i

Me

CH(Me)

4-Cl

O

A-isomer

1.5406

1-595

CO

2

Et

Pr-i

Me

CH(Me)

4-Cl

O

B-isomer

Not

Measurable

1-596

Pr-i

Me

CH

2

H

O

1-597

Pr-i

Me

CH

2

4-F

O

171-173

1-598

Pr-i

Me

CH

2

4-Cl

O

167-168

1-599

Pr-i

Me

CH

2

4-Me

O

141-142

1-600

Pr-i

Me

CH(Me)

4-Cl

O

95-98

1-601

Pr-i

Me

CH

2

H

O

1-602

Pr-i

Me

CH

2

4-F

O

123-124

1-603

Pr-i

Me

CH

2

4-Cl

O

133-134

1-604

Pr-i

Me

CH

2

4-Me

O

103-104

1-605

Pr-i

Me

CH(Me)

4-Cl

O

1-606

Et

Pr-n

CH

2

C≡CH

CH

2

H

O

58-59

1-607

Et

Pr-n

CH

2

C≡CH

CH

2

4-F

O

76-77

1-608

Et

Pr-n

CH

2

C≡CH

CH

2

4-Cl

O

111-113

1-609

Et

Pr-n

CH

2

C≡CH

CH

2

4-Me

O

90-91

1-610

Pr-i

Pr-n

CH

2

C≡CH

CH

2

H

O

1-611

Pr-i

Pr-n

CH

2

C≡CH

CH

2

4-F

O

70-71

1-612

Pr-i

Pr-n

CH

2

C≡CH

CH

2

4-Cl

O

TABLE 19

Dia-

m.p. (° C.)

Compound

stereo-

or refractive

No.

R

1

R

2

R

3

Z

Xn

Q

mer

index (n

D

20

)

1-613

Pr-n

Pr-i

CH

2

C≡CH

CH

2

4-Me

O

1-614

CF

3

Pr-i

CH

2

C≡CH

CH

2

3,4-F

2

O

133-134

1-615

CF

3

Pr-i

CH

2

C≡CH

CH

2

2-F-4-Cl

O

122-124

1-616

Pr-n

Pr-i

CH

2

C≡CH

CH

2

H

O

118-119

1-617

Pr-n

Pr-i

CH

2

C≡CH

CH

2

4-F

O

106-107

1-618

Pr-n

Pr-i

CH

2

C≡CH

CH

2

4-Cl

O

111-112

1-619

Pr-n

Pr-i

CH

2

C≡CH

CH

2

4-Me

O

98-99

1-620

CF

3

Bu-t

CH

2

C≡CH

CH

2

4-F

O

93-96

1-621

Pr-i

Pr-i

CH

2

C≡CH

CH

2

H

O

137-138

1-622

Pr-i

Pr-i

CH

2

C≡CH

CH

2

4-F

O

159-161

1-623

Pr-i

Pr-i

CH

2

C≡CH

CH

2

4-Cl

O

131-134

1-624

Pr-i

Pr-i

CH

2

C≡CH

CH

2

4-Me

O

153-154

1-625

CH(OMe)

2

Pr-i

Me

CH(Me)

4-Cl

O

1.5371

1-626

Et

Bu-t

CH

2

C≡CH

CH

2

H

O

84-88

1-627

Et

Bu-t

CH

2

C≡CH

CH

2

4-F

O

127-130

1-628

Et

Bu-t

CH

2

C≡CH

CH

2

4-Cl

O

1-629

Et

Bu-t

CH

2

C≡CH

CH

2

4-Me

O

1-630

COPr-i

Pr-i

Me

CH(Me)

4-Cl

O

116-117

1-631

C(Me)═NOMe

Pr-i

Me

CH(Me)

4-Cl

O

1.5423

1-632

CN

Bu-t

Me

CH(Me)

4-Cl

O

A-isomer

130-132

1-633

COMe

Bu-t

Me

CH(Me)

4-Cl

O

1.5439

1-634

CF

3

Pr-i

Me

CH(Me)

H

O

A-isomer

128-131

(S-isomer)

1-635

CF

3

Pr-i

Me

CH(Me)

H

O

B-isomer

1.5091

(S-isomer)

1-636

CF

2

Cl

Pr-i

Me

O

4-Me

O

112-115

1-637

CF

2

Cl

Pr-i

Me

O

4-OMe

O

123-126

1-638

CF

2

Cl

Pr-i

Me

O

4-Br

O

108-111

1-639

CF

2

Cl

Pr-i

Me

OCH

2

H

O

1.5251

1-640

CF

2

Cl

Pr-i

Me

O

4-NO

2

O

1.5301

1-641

CF

2

Cl

Pr-i

Me

O

H

S

132-135

1-642

Et

Pr-i

Me

O

4-Cl

O

80-83

1-643

Pr-n

Pr-n

Me

O

4-Cl

O

1.5379

1-644

Pr-n

Pr-i

Me

O

4-Cl

O

1.5367

1-645

Me

Me

Me

O

4-Cl

O

90-93

1-646

Et

Et

Me

O

4-Cl

O

1.5468

TABLE 20

m.p. (° C.) or

Dia-

refractive

Compound

stereo-

index

No.

R

1

R

2

R

3

Z

Xn

Q

mer

(n

D

20

)

1-647

Pr-i

Pr-i

Me

O

H

O

1.5331

1-648

Pr-i

Pr-i

Me

O

4-Me

O

1.5346

1-649

Pr-i

Pr-i

Me

O

4-OMe

O

1.5282

1-650

Pr-i

Pr-i

Me

O

4-F

P

1.5169

1-651

Et

CH(Me)SMe

Me

CH

2

H

O

Not Measurable

1-652

Et

CH(Me)SMe

Me

CH

2

4-F

O

Not Measurable

1-653

Et

CH(Me)SMe

Me

CH

2

4-Cl

O

88-91

1-654

Et

CH(Me)SMe

Me

CH

2

4-Me

O

1.5676

1-655

NHCO

2

CH

3

Ph

Pr-i

Me

CH(Me)

4-Cl

O

161-163

1-656

Et

C(Me)

2

CO

2

Me

Me

CH

2

4-Cl

O

1.5502

1-657

SOMe

Pr-i

Me

CH

2

4-Cl

O

1-658

SO

2

Me

Pr-i

Me

CH

2

4-Cl

O

1-659

OEt

Pr-i

Me

CH

2

H

O

1-660

OEt

Pr-i

Me

CH

2

4-F

O

1-661

OEt

Pr-i

Me

CH

2

4-Cl

O

1-662

OEt

Pr-i

Me

CH

2

4-Me

O

1-663

OCHF

2

Pr-i

Me

CH

2

H

O

1-664

OCHF

2

Pr-i

Me

CH

2

4-F

O

1-655

OCHF

2

Pr-i

Me

CH

2

4-Cl

O

1-666

OCHF

2

Pr-i

Me

CH

2

4-Me

O

1-667

SOCH

2

CH═CH

2

Pr-i

Me

CH

2

4-Cl

O

1-668

SOCH

2

C≡CH

Pr-i

Me

CH

2

4-Cl

O

1-669

OCH

2

CH≡CH

2

Pr-i

Me

CH

2

H

O

1-670

OCH

2

CH═CH

2

Pr-i

Me

CH

2

4-F

O

1-671

OCH

2

CH═CH

2

Pr-i

Me

CH

2

4-Cl

O

1-672

OCH

2

CH═CH

2

Pr-i

Me

CH

2

4-Me

O

1-673

OCH

2

C≡CH

Pr-i

Me

CH

2

H

O

1-674

OCH

2

C≡CH

Pr-i

Me

CH

2

4-F

O

1-675

OCH

2

C≡CH

Pr-i

Me

CH

2

4-Cl

O

1-676

OCH

3

C≡CH

Pr-i

Me

CH

2

4-Me

O

1-677

OPr-c

Pr-i

Me

CH

2

H

O

1-678

OPr-c

Pr-i

Me

CH

2

4-F

O

1-679

OPr-c

Pr-i

Me

CH

2

4-Cl

O

1-680

OPr-c

Pr-i

Me

CH

2

4-Me

O

1-681

SPr-c

Pr-i

Me

CH

2

4-Cl

O

TABLE 21

m.p. (° C.) or

Dia-

refractive

Compound

stereo-

index

No.

R

1

R

2

R

3

Z

Xn

Q

mer

(n

D

20

)

1-682

SOPr-c

Pr-i

Me

CH

2

4-Cl

O

1-683

SO

2

Pr-c

Pr-i

Me

CH

2

4-Cl

O

1-684

N(Me)

2

Pr-i

Me

CH

2

4-Cl

O

1-685

NHMe

Pr-i

Me

CH

2

4-Cl

O

1-686

NH(CHF

2

)

Pr-i

Me

CH

2

4-Cl

O

1-687

NH(CH

2

OMe)

Pr-i

Me

CH

2

4-Cl

O

1-688

NH(CH

2

SMe)

Pr-i

Me

CH

2

4-Cl

O

1-689

NHPr-c

Pr-i

Me

CH

2

4-Cl

O

1-690

NHCOMe

Pr-i

Me

CH

2

4-Cl

O

1-691

NHSO

2

Me

Pr-i

Me

CH

2

4-Cl

O

1-692

NHCO

2

Me

Pr-i

Me

CH

2

4-Cl

O

1-693

NH(CH

2

CH═CH

2

)

Pr-i

Me

CH

2

4-Cl

O

1-694

NH(CH

2

C≡CH)

Pr-i

Me

CH

2

4-Cl

O

1-695

CH(Me)CH═CH

2

Pr-i

Me

CH

2

4-Cl

O

1-696

CH

2

C≡CH

Pr-i

Me

CH

2

4-Cl

O

1-697

OH

Pr-i

Me

CH

2

4-Cl

O

1-698

CO

2

H

Pr-i

Me

CH

2

4-Cl

O

1-699

CON(—C

4

H

8

)

Pr-i

Me

CH

2

4-Cl

O

1-700

CONH(CH

2

CH═CH

2

)

Pr-i

Me

CH

2

4-Cl

O

1-701

Pr-i

CH(Me)CH═CH

2

Me

CH

2

4-Cl

O

1-702

Pr-i

CH

2

C≡CH

Me

CH

2

4-Cl

O

1-703

Et

CHClMe

Me

CH

2

4-Cl

O

1-704

Et

OEt

Me

CH

2

4-Cl

O

1-705

Et

CH(Me)CN

Me

CH

2

4-Cl

O

1-706

Et

CO

2

Me

Me

CH

2

4-Cl

O

1-707

Et

CHMeN(Me)

2

Me

CH

2

4-Cl

O

1-708

Et

CON(Me)

2

Me

CH

3

4-Cl

O

1-709

Et

CHMeCONMe

2

Me

CH

2

4-Cl

O

1-710

Et

Pr-i

Me

CH

2

4-OCH

2

CH═CH

2

O

1-711

Et

Pr-i

Me

CH

2

4-OPr-c

O

1-712

Et

Pr-i

Me

CH

2

4-COMe

O

TABLE 22

m.p. (° C.) or

Dia-

refractive

Compound

stereo-

index

No.

R

1

R

2

R

3

Z

Xn

Q

mer

(n

D

20

)

1-713

Et

Pr-i

Me

CH

2

4-CO

2

Me

O

1-714

Et

Pr-i

Me

CH

2

4-SOMe

O

1-715

Et

Pr-i

N(NMe

2

)

CH

2

4-Cl

O

1-716

Et

Pr-i

Me

CH

2

4-CH

2

CH═CH

2

O

1-717

Et

Pr-i

Me

CH

2

4-CH

2

C≡CH

O

1-718

CO

2

H

Pr-i

N(Me)

CH(Me)

4-Cl

O

168-170

1-719

CH═CHCO

2

Et

Pr-i

Me

CH(Me)

4-Cl

O

57-59

1-720

CF

3

Pr-i

CH

2

C≡CH

CH

2

4-Me

O

111-113

1-721

COEt

Pr-i

Me

CH(Me)

H

O

1-722

COEt

Pr-i

Me

CH(Me)

4-F

O

1-723

COEt

Pr-i

Me

CH(Me)

4-Cl

O

1-724

COEt

Pr-i

Me

CH(Me)

4-Me

O

1-725

COEt

Pr-n

Me

CH

2

H

O

1-726

COEt

Pr-n

Me

CH

2

4-F

O

1-727

COEt

Pr-n

Me

CH

2

4-Cl

O

1-728

COEt

Pr-n

Me

CH

2

4-Me

O

1-729

COEt

Pr-i

CH

2

C≡CH

CH(Me)

H

O

1-730

COEt

Pr-i

CH

2

C≡CH

CH(Me)

4-F

O

1-731

COEt

Pr-i

CH

2

C≡CH

CH(Me)

4-Cl

O

1-732

COEt

Pr-i

CH

2

C≡CH

CH(Me)

4-Me

O

1-733

COEt

Pr-n

CH

2

C≡CH

CH

2

H

O

1-734

COEt

Pr-n

CH

2

C≡CH

CH

2

4-F

O

1-735

COEt

Pr-n

CH

2

C≡CH

CH

2

4-Cl

O

1-736

COEt

Pr-n

CH

2

C≡CH

CH

2

4-Me

O

1-737

COMe

Pr-n

Me

CH

2

H

O

1-738

COMe

Pr-n

Me

CH

2

4-F

O

1-739

COMe

Pr-n

Me

CH

2

4-Cl

O

1-740

COMe

Pr-n

Me

CH

2

4-Me

O

1-741

COMe

Pr-i

CH

2

C≡CH

CH(Me)

H

O

1-742

COMe

Pr-i

CH

2

C≡CH

CH(Me)

4-F

O

1-743

COMe

Pr-i

CH

2

C≡CH

CH(Me)

4-Cl

O

1-744

COMe

Pr-i

CH

2

C≡CH

CH(Me)

4-Me

O

1-745

COMe

Pr-n

CH

2

C≡CH

CH

2

H

O

1-746

COMe

Pr-n

CH

2

C≡CH

CH

2

4-F

O

1-747

COMe

Pr-n

CH

2

C≡CH

CH

2

4-Cl

O

1-748

COMe

Pr-n

CH

2

C≡CH

CH

2

4-Me

O

TABLE 23

m.p. (° C.) or

Dia-

refractive

Compound

stereo-

index

No.

R

1

R

2

R

3

Z

Xn

Q

mer

(n

D

20

)

1-749

COPr-i

Pr-i

Me

CH(Me)

H

O

1-750

COPr-i

Pr-i

Me

CH(Me)

4-F

O

1-751

COPr-i

Pr-i

Me

CH(Me)

4-Me

O

1-752

COPr-i

Pr-n

Me

CH

2

H

O

1-753

COPr-i

Pr-n

Me

CH

2

4-F

O

1-754

COPr-i

Pr-n

Me

CH

2

4-Cl

O

1-755

COPr-i

Pr-n

Me

CH

2

4-Me

O

1-756

COPr-i

Pr-i

CH

2

C≡CH

CH(Me)

H

O

1-757

COPr-i

Pr-i

CH

2

C≡CH

CH(Me)

4-F

O

1-758

COPr-i

Pr-i

CH

2

C≡CH

CH(Me)

4-Cl

O

1-759

COPr-i

Pr-i

CH

2

C≡CH

CH(Me)

4-Me

O

1-760

COPr-i

Pr-n

CH

2

C≡CH

CH

2

H

O

1-761

COPr-i

Pr-n

CH

2

C≡CH

CH

2

4-F

O

1-762

COPr-i

Pr-n

CH

2

C≡CH

CH

2

4-Cl

O

1-763

COPr-i

Pr-n

CH

2

C≡CH

CH

2

4-Me

O

1-764

OEt

Pr-n

Me

CH

2

H

O

1-765

OEt

Pr-n

Me

CH

2

4-F

O

1-766

OEt

Pr-n

Me

CH

2

4-Cl

O

1-767

OEt

Pr-n

Me

CH

2

4-Me

O

1-768

OEt

Pr-i

CH

2

C≡CH

CH(Me)

H

O

1-769

OEt

Pr-i

CH

2

C≡CH

CH(Me)

4-F

O

1-770

OEt

Pr-i

CH

2

C≡CH

CH(Me)

4-Cl

O

1-771

OEt

Pr-i

CH

2

C≡CH

CH(Me)

4-Me

O

1-772

OPr-i

Pr-i

Me

CH(Me)

H

O

1-773

OPr-i

Pr-i

Me

CH(Me)

4-F

O

1-774

OPr-i

Pr-i

Me

CH(Me)

4-Cl

O

1-775

OPr-i

Pr-i

Me

CH(Me)

4-Me

O

1-776

OPr-i

Pr-n

Me

CH

2

H

O

1-777

OPr-i

Pr-n

Me

CH

2

4-F

O

1-778

OPr-i

Pr-n

Me

CH

2

4-Cl

O

1-779

OPr-i

Pr-n

Me

CH

2

4-Me

O

1-780

OPr-i

Pr-i

CH

2

C≡CH

CH(Me)

H

O

1-781

OPr-i

Pr-i

CH

2

C≡CH

CH(Me)

4-F

O

1-782

OPr-i

Pr-i

CH

2

C≡CH

CH(Me)

4-Cl

O

1-783

OPr-i

Pr-i

CH

2

C≡CH

CH(Me)

4-Me

O

1-784

Et

Ph

Me

CH

2

H

O

1-785

Et

Ph

Me

CH

2

4-F

O

TABLE 24

m.p. (° C.) or

Dia-

refractive

Compound

stereo-

index

No.

R

1

R

2

R

3

Z

Xn

Q

mer

(n

D

20

)

1-786

Et

Ph

Me

CH

2

4-Cl

O

1-787

Et

Ph

Me

CH

2

4-Me

O

1-788

N(Me)

2

Pr-i

Me

CH

2

H

O

63-66

1-789

N(Me)

2

Pr-i

Me

CH

2

4-F

O

1-790

N(Me)

2

Pr-i

Me

CH

2

4-Me

O

1-791

N(Me)

2

Pr-i

Me

CH(Me)

H

O

1-792

N(Me)

2

Pr-i

Me

CH(Me)

4-F

O

1-793

N(Me)

2

Pr-i

Me

CH(Me)

4-Cl

O

1-794

N(Me)

2

Pr-i

Me

CH(Me)

4-Me

O

1-795

CF

3

Pr-i

Me

N(Me)CH

2

H

O

1-796

CF

3

Pr-i

Me

N(Me)CH

2

4-F

O

1-797

CF

3

Pr-i

Me

N(Me)CH

2

4-Me

O

1-798

Et

Pr-i

Me

N(Me)CH

2

H

O

1-799

Et

Pr-i

Me

N(Me)CH

2

4-F

O

1-800

Et

Pr-i

Me

N(Me)CH

2

4-Cl

O

1-801

Et

Pr-i

Me

N(Me)CH

2

4-Me

O

1-802

Pr-i

Pr-i

Me

N(Me)CH

2

H

O

1-803

Pr-i

Pr-i

Me

N(Me)CH

2

4-F

O

1-804

Pr-i

Pr-i

Me

N(Me)CH

2

4-Cl

O

1-805

Pr-i

Pr-i

Me

N(Me)CH

2

4-Me

O

1-806

C(Me)═CH

2

Pr-n

Me

CH

2

H

O

1-807

C(Me)═CH

2

Pr-n

Me

CH

2

4-F

O

1-808

C(Me)═CH

2

Pr-n

Me

CH

2

4-Cl

O

1-809

C(Me)═CH

2

Pr-n

Me

CH

2

4-Me

O

1-810

Pr-n

C(Me)═CH

2

Me

CH

2

H

O

1-811

Pr-n

C(Me)═CH

2

Me

CH

2

4-F

O

1-812

Pr-n

C(Me)═CH

2

Me

CH

2

4-Cl

O

1-813

Pr-n

C(Me)═CH

2

Me

CH

2

4-Me

O

1-814

Et

C(Me)═CH

2

Me

CH

2

H

O

1-815

Et

C(Me)═CH

2

Me

CH

2

4-F

O

1-816

Et

C(Me)═CH

2

Me

CH

2

4-Cl

O

1-817

Et

C(Me)═CH

2

Me

CH

2

4-Me

O

1-818

Et

OEt

Me

CH(Me)

4-Cl

O

1-819

Et

CH(Me)CN

Me

CH(Me)

4-Cl

O

1-820

Et

CO

2

Me

Me

CH(Me)

4-Cl

O

1-821

Et

CHMeN(Me)

2

Me

CH(Me)

4-Cl

O

TABLE 25

m.p. (° C.) or

Dia-

refractive

Compound

stereo-

index

No.

R

1

R

2

R

3

Z

Xn

Q

mer

(n

D

20

)

1-822

Et

CON(Me)

2

Me

CH(Me)

4-Cl

O

1-823

Et

CHMeCONMe

2

Me

CH(Me)

4-Cl

O

1-824

Bu-t

Et

CH

2

C≡CH

CH

2

H

O

1-825

Bu-t

Et

CH

2

C≡CH

CH

2

4-F

O

1-826

Bu-t

Et

CH

2

C≡CH

CH

2

4-Cl

O

1-827

Bu-t

Et

CH

2

C≡CH

CH

2

4-Me

O

1-828

COPr-c

Pr-n

Me

CH

2

H

O

1-829

COPr-c

Pr-n

Me

CH

2

4-F

O

1-830

COPr-c

Pr-n

Me

CH

2

4-Cl

O

1-831

COPr-c

Pr-n

Me

CH

2

4-Me

O

1-832

Et

C(Me)

2

OH

Me

CH

2

H

O

1-833

Et

C(Me)

2

OH

Me

CH

2

4-F

O

1-834

Et

C(Me)

2

OH

Me

CH

2

4-Cl

O

1-835

Et

C(Me)

2

OH

Me

CH

2

4-Me

O

1-836

Et

C(Me)

2

Cl

Me

CH

2

H

O

1-837

Et

C(Me)

2

Cl

Me

CH

2

4-F

O

1-838

Et

C(Me)

2

Cl

Me

CH

2

4-Cl

O

1-839

Et

C(Me)

2

Cl

Me

CH

2

4-Me

O

1-840

N(Me)CH

2

C≡CH

Pr-i

Me

CH

2

H

O

1-841

N(Me)CH

2

C≡CH

Pr-i

Me

CH

2

4-F

O

1-842

N(Me)CH

2

C≡CH

Pr-i

Me

CH

2

4-Cl

O

1-843

N(Me)CH

2

C≡CH

Pr-i

Me

CH

2

4-Me

O

1-844

N(Me)CH

2

C≡CH

Pr-i

Me

CH(Me)

H

O

1-845

N(Me)CH

2

C≡CH

Pr-i

Me

CH(Me)

4-F

O

1-846

N(Me)CH

2

C≡CH

Pr-i

Me

CH(Me)

4-Cl

O

1-847

N(Me)CH

2

C≡CH

Pr-i

Me

CH(Me)

4-Me

O

1-848

CH

2

CF

3

Pr-i

Me

CH

2

H

O

1-849

CH

2

CF

3

Pr-i

Me

CH

2

4-F

O

1-850

CH

2

CF

3

Pr-i

Me

CH

2

4-Cl

O

1-851

CH

2

CF

3

Pr-i

Me

CH

2

4-Me

O

1-852

CF

2

CF

3

Pr-i

Me

CH

2

H

O

106-108

1-853

CF

2

CF

3

Pr-i

Me

CH

2

4-F

O

118-119

1-854

CF

2

CF

3

Pr-i

Me

CH

2

4-Cl

O

122-123

1-855

CF

2

CF

3

Pr-i

Me

CH

2

4-Me

O

68-69

1-856

OCF

3

Pr-i

Me

CH

2

H

O

1-857

OCF

3

Pr-i

Me

CH

2

4-F

O

TABLE 26

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Xn

Q

Diastereomer

(n

D

20

)

1-858

OCF

3

Pr-i

Me

CH

2

4-Cl

O

1-859

OCF

3

Pr-i

Me

CH

2

4-Me

O

1-860

Et

CH(Me)OMe

Me

CH

2

H

O

1-861

Et

CH(Me)OMe

Me

CH

2

4-F

O

1-862

Et

CH(Me)OMe

Me

CH

2

4-Cl

O

1-863

Et

CH(Me)OMe

Me

CH

2

4-Me

O

1-864

Et

CH(Me)CN

Me

CH

2

H

O

1-865

Et

CH(Me)CN

Me

CH

2

4-F

O

1-866

Et

CH(Me)CN

Me

CH

2

4-Me

O

1-867

Et

Pr-i

CH

2

C≡CH

CH

2

3,4-F

2

O

1-868

Et

Pr-i

CH

2

C≡CH

CH

2

2,4-F

2

O

1-869

Et

Pr-i

CH

2

C≡CH

CH

2

3-F

O

1-870

CF

3

Pr-i

CH

2

C≡CH

CH

2

2,4-F

2

O

λ-isomer

110-113

1-871

CF

3

Pr-i

Me

CH(Me)

H

O

B-isomer

144-146

(R-isomer)

1-872

CF

3

Pr-i

Me

CH(Me)

H

O

1.5164

(R-isomer)

1-873

CClF

2

Pr-i

Me

N(Me)

H

O

1.5341

1-874

CF

3

Pr-i

Me

NHN(Me)

H

O

72-75

1-875

CH

2

CH(OMe)

2

Pr-i

Me

CH

2

4-Cl

O

90-91

1-876

CH

2

CN

Pr-i

Me

CH

2

4-Cl

O

106-107

1-877

Et

Me

CH

2

4-Cl

O

1.5552

1-878

COMe

Et

Me

CH

2

4-Cl

O

1.5612

1-879

CMe═NOMe

Et

Me

CH

2

4-Cl

O

81-83

1-880

CF

3

Pr-i

Me

N(Me)CH

2

H

O

63-64

1-881

CH═NOMe

Pr-n

Me

CH(Me)

4-Cl

O

Not

Measurable

1-882

CN

Pr-n

Me

CH(Me)

4-Cl

O

103-106

1-883

Et

Me

CH

2

4-Cl

O

161-162

1-884

Et

CMe(OMe)

2

Me

CH

2

H

O

Not

Measurable

1-885

Et

CMe═NOMe

Me

CH

2

H

O

Not

Measurable

1-886

Et

CMe(OMe)

2

Me

CH

2

4-F

O

Not

Measurable

1-887

Et

COMe

Me

CH

2

4-F

O

71-73

1-888

Et

CMe═NOMe

Me

CH

2

4-F

O

1.5443

1-889

COOH

Pr-i

Me

CH

2

4-Cl

O

139-141

1-890

CN

Bu-t

Me

CHMe

4-Cl

O

106-108

TABLE 27

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Ar

Q

(n

D

20

)

2-1

CF

3

Pr-i

Me

CH

2

2-napthyl

O

137-138

2-2

CF

3

Pr-i

Me

CH

2

3-thienyl

O

37-38

2-3

CF

3

Pr-i

Me

CH

2

2-pyridyl

O

99-100

2-4

CF

3

Pr-i

Me

CH

2

3-pyridyl

O

93-96

2-5

CF

3

Pr-i

Me

CH

2

4-pyridyl

O

115-118

2-6

CF

3

Pr-i

Me

CH

2

2-thienyl

O

51-54

2-7

CHF

3

Pr-i

Et

CH

2

2-thienyl

O

69-71

2-8

CHF

3

Pr-i

Et

CH

2

3-thienyl

O

83-85

2-9

CF

3

Pr-i

Et

CH

2

2-thienyl

O

1.5197

2-10

CF

3

Pr-i

Et

CH

2

3-thienyl

O

1.5208

2-11

CF

3

Bu-s

Me

CH

2

2-thienyl

O

1.5215

2-12

CF

3

Bu-s

Me

CH

2

3-thienyl

O

1.5229

2-13

CF

3

Bu-t

Me

CH

2

2-thienyl

O

1.5121

2-14

CF

3

Bu-t

Me

CH

2

3-thienyl

O

58-62

2-15

CF

3

Pr-i

Me

CH(Me)

2-thienyl

O

2-16

CF

3

Pr-i

Me

CH(Me)

3-thienyl

O

2-17

CF

3

Bu-t

Me

CH(Me)

2-thienyl

O

2-18

CF

3

Bu-t

Me

CH(Me)

3-thienyl

O

2-19

CF

3

Ph

Me

CH

2

2-thienyl

O

139-142

2-20

CF

3

Ph

Me

CH

2

3-thienyl

O

142-145

2-21

SMe

Pr-i

Me

CH

2

2-thienyl

O

2-22

SMe

Pr-i

Me

CH

2

3-thienyl

O

2-23

Pr-i

Pr-i

Me

CH

2

2-thienyl

O

79-81

2-24

Pr-i

Pr-i

Me

CH

2

3-thienyl

O

101-103

2-25

CF

3

Pr-i

Me

CH

2

5-Cl-2-thienyl

O

94-95

2-26

CF

3

Pr-i

Me

CH

2

5-Me-2-thienyl

O

2-27

SMe

Pr-i

Me

CH

2

5-Cl-2-thienyl

O

2-28

SMe

Pr-i

Me

CH

2

5-Me-2-thienyl

O

TABLE 28

m.p.

(° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Ar

Q

(n

D

20

)

2-29

Pr-i

Pr-i

Me

CH

2

5-Cl-2-thienyl

O

2-30

Pr-i

Pr-i

Me

CH

2

5-Me-2-thienyl

O

2-31

CF

3

Ph

Me

CH

2

5-Cl-2-thienyl

O

79-81

2-32

CF

3

Ph

Me

CH

2

5-Me-2-thienyl

O

111-113

2-33

CF

3

Ph

Me

CH(Me)

2-thienyl

O

2-34

CF

3

Ph

Me

CH(Me)

3-thienyl

O

2-35

CF

3

Pr-i

Me

CH

2

5-CF

3

-2-thienyl

O

2-36

CF

3

Pr-i

Me

CH

2

5-F-2-thienyl

O

2-37

CF

3

Pr-i

Me

CH

2

3-Cl-2-thienyl

O

2-38

CF

3

Pr-i

Me

CH

2

3-F-2-thienyl

O

2-39

CF

3

Pr-i

Me

CH

2

5-Cl-3-thienyl

O

2-40

CF

3

Pr-i

Me

CH

2

5-Me-3-thienyl

O

2-41

CF

3

Pr-i

Me

CH

2

4-Br-pyrazol-1-yl

O

160-161

2-42

CF

3

Bu-t

Me

CH

2

5-Cl-2-thienyl

O

106-107

2-43

CF

3

Pr-i

Me

CH

2

O

5-Cl-2-pyridyl

O

145-147

2-44

CF

3

Pr-i

Me

CH

2

O

5-Cl-3-pyridyl

O

120-122

2-45

CF

3

Pr-i

Me

CH

2

O

3-Cl-5-CF

3

-pyridin-2-yl

O

138-141

2-46

CF

3

Pr-i

Me

CH

2

O

1-Me-3-CF

3

5-Pyrazolyl

O

108-112

2-47

CF

3

Pr-i

Me

CH

2

O

5-CF

3

-1,3,4-thiaziazol-2-yl

O

121-122

2-48

CF

3

Pr-i

Me

CH

2

O

2-benzothiazolyl

O

192-195

2-49

CF

3

Pr-i

Me

CH

2

O

4-CF

3

-pyridin-2-yl

O

164-167

2-50

CF

3

Pr-i

Me

CH

2

5-Me-2-thienyl

O

73-75

2-51

CF

3

Bu-i

Me

CH

2

2-thienyl

O

68-70

2-52

CF

3

Bu-i

Me

CH

2

3-thienyl

O

81-82

2-53

CF

3

Bu-i

Me

CH

2

5-Me-2-thienyl

O

94-98

2-54

CF

3

Pr-i

Me

CH

2

Pr-e

O

86-87

2-55

CF

3

Me

CH

2

2-thienyl

O

92-93

2-56

CF

3

Me

CH

2

3-thienyl

O

111-112

2-57

CF

3

Bu-s

Me

CH

2

5-Cl-2-thienyl

O

1.5295

TABLE 29

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Ar

Q

(n

D

20

)

2-58

CF

3

Me

CH

2

5-Cl-2-thienyl

O

Not Measurable

2-59

CF

3

Me

CH

2

5-Me-2-thienyl

O

71-74

2-60

CF

3

Pr-i

Me

CH(Me)

5-Me-2-thienyl

O

1.5141

2-61

CF

3

Pr-i

Me

CH(Me)

5-Br-2-thienyl

O

1.5331

2-62

CF

3

Pr-i

Me

CH(Me)

2-thienyl

O

Not more

than 30° C.

2-63

CF

3

Pr-i

Me

N(Me)

3-thienyl

O

1.5244

2-64

CF

3

Pr-i

Me

NH

2-benzothiazolyl

O

180-182

2-65

CF

3

Pr-i

Me

N(Me)

5-Cl-pyridin-2-yl

O

39-40

2-66

CF

3

Pr-i

Me

NH

cycrohexyl

O

110-112

2-67

CF

3

Pr-i

Me

N(Me)

3-Me-5-isoxazolyl

O

1.4939

2-68

CF

3

Pr-i

Me

N(Me)

4-MeO-6-Me-pyrimidin-2-yl

O

107-110

2-69

CF

3

Pr-i

Me

N(Me)

4,6-(MeO)

2

-1,3,5-triazinyl

O

112-113

2-70

CF

3

Pr-i

Me

N(Me)

6-MeO-pyridin-3-yl

O

1.5079

2-71

Pr-i

Pr-i

Me

CH

2

5-Cl-2-thienyl

O

112-115

2-72

CF

3

Pr-i

Me

N(Me)

cycrohexyl

O

98-100

2-73

Et

Pr-i

CH

2

C≡CH

CH

2

5-Cl-2-thienyl

O

90-91

2-74

CF

3

Pr-i

CH

2

C≡CH

CH

2

5-Cl-2-thienyl

O

117-118

2-75

Et

Pr-i

Me

CH

2

5-Cl-2-thienyl

O

Not

Measurable

2-76

Pr-i

CH

2

OMe

Me

CH

2

5-Cl-2-thienyl

O

1.5488

2-77

CH

2

OMe

Pr-i

Me

CH

2

5-Cl-2-thienyl

O

1.5508

2-78

CF

3

Pr-i

CH

2

C≡CH

CH

2

3-thienyl

O

112-114

2-79

Pr-i

Pr-i

CH

2

C≡CH

CH

2

3-thienyl

O

128-131

2-80

CF

2

Cl

Pr-i

Me

O

1-naphtyl

O

123-126

2-81

CF

3

Pr-i

Me

CH

2

5-CF

3

-1,3,4-thiadizol-2-yl

O

2-82

CF

3

Pr-i

Me

CH

2

4-CF

3

-1,3,4-imidazol-2-yl

O

2-83

CF

3

Pr-i

Me

CH

2

2-Cl-5-oxazolyl

O

2-84

CF

3

Pr-i

Me

CH

2

2-Cl-5-thiazolyl

O

2-85

CF

3

Pr-i

Me

CH

2

5-Cl-2-furyl

O

TABLE 30

m.p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Ar

Q

(n

D

20

)

2-86

CF

3

Pr-i

Me

CH

2

2-benzoxazolyl

O

2-87

Et

Pr-i

Me

CH

2

2-thienyl

O

2-88

Et

Pr-i

Me

CH

2

3-thienyl

O

2-89

Et

Pr-i

Me

CH

2

5-Me-2-thienyl

O

2-90

Et

Pr-i

Me

CH(Me)

2-thienyl

O

2-91

Et

Pr-i

Me

CH(Me)

3-thienyl

O

2-92

Et

Pr-i

Me

CH(Me)

5-Cl-2-thienyl

O

2-93

Et

Pr-i

Me

CH(Me)

5-Me-2-thienyl

O

2-94

Et

Pr-i

CH

2

C≡CH

CH

2

2-thienyl

O

2-95

Et

Pr-i

CH

2

C≡CH

CH

2

3-thienyl

O

2-96

Et

Pr-i

CH

2

C≡CH

CH

2

5-Me-2-thienyl

O

2-97

Et

Bu-s

Me

CH

2

2-thienyl

O

2-98

Et

Bu-s

Me

CH

2

3-thienyl

O

2-99

Et

Bu-t

Me

CH

2

2-thienyl

O

2-100

Et

Bu-t

Me

CH

2

3-thienyl

O

2-101

Et

Bu-s

CH

2

C≡CH

CH

2

2-thienyl

O

2-102

Et

Bu-s

CH

2

C≡CH

CH

2

3-thienyl

O

2-103

Et

Bu-t

CH

2

C≡CH

CH

2

2-thienyl

O

2-104

Et

Bu-t

CH

2

C≡CH

CH

2

3-thienyl

O

2-105

CF

3

Pr-i

Me

N(Me)

2-thienyl

O

2-106

CF

3

Pr-i

Me

N(Me)

5-Cl-2-thienyl

O

2-107

CF

3

Pr-i

Me

N(Me)

5-Me-2-thienyl

O

2-108

Et

Pr-i

Me

N(Me)

2-thienyl

O

2-109

Et

Pr-i

Me

N(Me)

3-thienyl

O

2-110

Et

Pr-i

Me

N(Me)

5-Cl-2-thienyl

O

2-111

Et

Pr-i

Me

N(Me)

5-Me-2-thienyl

O

2-112

CF

3

Pr-i

Me

NHCH

2

2-thienyl

O

110-112

TABLE 31

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Xn

R

7

R

8

(n

D

20

)

3-1

CF

3

Pr-i

Me

CH

2

H

H

Me

99-101

3-2

CF

3

Pr-i

Me

CH

2

4-F

H

Me

74-75

3-3

CF

3

Pr-i

Me

CH

2

4-Cl

H

Me

67-68

3-4

CF

3

Pr-i

Me

CH

2

4-Me

H

Me

85-86

3-5

CF

3

Pr-i

Me

CH

2

H

H

Pr-c

144-145

3-6

CF

3

Pr-i

Me

CH

2

4-F

H

Pr-c

131-132

3-7

CF

3

Pr-i

Me

CH

2

4-Cl

H

Pr-c

99-100

3-8

CF

3

Pr-i

Me

CH

2

4-Me

H

Pr-c

82-83

3-9

CF

3

Pr-i

Me

CH

2

H

Me

H

3-10

CF

3

Pr-i

Me

CH

2

4-F

Me

H

3-11

CF

3

Pr-i

Me

CH

2

4-Cl

Me

H

3-12

CF

3

Pr-i

Me

CH

2

4-Me

Me

H

3-13

Me

Pr-i

Me

CH

2

H

Me

H

3-14

Me

Pr-i

Me

CH

2

4-F

Me

H

3-15

Me

Pr-i

Me

CH

2

4-Cl

Me

H

3-16

Me

Pr-i

Me

CH

2

4-Me

Me

H

3-17

Pr-i

Pr-i

Me

CH

2

H

Me

H

3-18

Pr-i

Pr-i

Me

CH

2

4-F

Me

H

3-19

Pr-i

Pr-i

Me

CH

2

4-Cl

Me

H

3-20

Pr-i

Pr-i

Me

CH

2

4-Me

Me

H

3-21

Me

Bu-t

Me

CH

2

H

Me

H

3-22

Me

Bu-t

Me

CH

2

4-F

Me

H

3-23

Me

Bu-t

Me

CH

2

4-Cl

Me

H

3-24

Me

Bu-t

Me

CH

2

4-Me

Me

H

3-25

Et

Et

Me

CH

2

H

Et

H

3-26

Et

Et

Me

CH

2

4-F

Et

H

TABLE 32

m.p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Z

Xn

R

7

R

8

(n

D

20

)

3-27

Et

Et

Me

CH

2

4-Cl

Et

H

3-28

Et

Et

Me

CH

2

4-Me

Et

H

3-29

CF

3

Pr-i

Me

CH

2

H

H

SMe

3-30

CF

3

Pr-i

Me

CH

2

4-F

H

SMe

3-31

CF

3

Pr-i

Me

CH

2

4-Cl

H

SMe

3-32

CF

3

Pr-i

Me

CH

2

4-Me

H

SMe

3-33

CF

3

Ph

Me

CH

2

H

Me

H

3-34

CF

3

Ph

Me

CH

2

4-F

Me

H

3-35

CF

3

Ph

Me

CH

2

4-Cl

Me

H

3-36

CF

3

Ph

Me

CH

2

4-Me

Me

H

3-37

CF

3

Pr-i

Me

CH

2

H

CF

3

H

3-38

CF

3

Pr-i

Me

CH

2

4-F

CF

3

H

3-39

CF

3

Pr-i

Me

CH

2

4-Cl

CF

3

H

3-40

CF

3

Pr-i

Me

CH

2

4-Me

CF

3

H

3-41

OMe

Pr-i

Me

CH

2

4-Cl

OMe

H

107-109

3-42

CF

3

Pr-i

Me

O

4-Cl

H

Me

104-107

3-43

CF

3

Pr-i

Me

O

4-Cl

H

Pr-c

1.5178

TABLE 33

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Ar

(n

D

20

)

4-1

CF

3

Pr-i

Me

Ph(4-Cl)

1.5246

4-2

Et

Pr-i

Me

Ph

1.5446

4-3

Et

Pr-i

Me

Ph(4-F)

1.5399

4-4

Et

Pr-i

Me

Ph(3-F)

1.541

4-5

Et

Pr-i

Me

Ph(2-F)

1.5441

4-6

Et

Pr-i

Me

Ph(4-Cl)

1.5562

4-7

Et

Pr-i

Me

Ph(4-Me)

1.5475

4-8

Et

Pr-i

Me

Ph(4-CN)

1.5527

4-9

Et

Pr-i

Me

Ph(4-OMe)

102-103

4-10

Et

Pr-i

Me

Ph(4-NO

2

)

106-107

4-11

Pr-i

Pr-i

Me

Ph(4-F)

93-95

4-12

CH

2

OMe

Pr-i

Me

Ph(4-F)

1.5365

4-13

CH(OEt)

2

Pr-i

Me

Ph(4-F)

1.5234

4-14

Et

Pr

CH

2

C≡CH

Ph(4-F)

1.5445

4-15

CF

3

Pr-i

Me

Ph

1.518

4-16

Pr-i

Pr-i

Me

Ph(4-CF

3

)

4-17

CF

3

Pr-i

Me

Ph(4-F)

4-18

CF

3

Pr-i

Me

Ph(3-F)

4-19

CF

3

Pr-i

Me

Ph(2-F)

4-20

CF

3

Pr-i

Me

Ph(4-Me)

4-21

CF

3

Pr-i

Me

Ph(4-CN)

4-22

CF

3

Pr-i

Me

Ph(4-OMe)

4-23

CF

3

Pr-i

Me

Ph(4-NO

2

)

4-24

CF

3

Pr-i

CH

2

C≡CH

Ph(4-F)

4-25

CF

3

Pr-i

Me

Ph(2-Me)

4-26

Et

Pr-i

Me

Ph(2-Me)

1.5512

4-27

CF

3

Pr-i

M

Ph(3-Me)

4-28

Et

Pr-i

Me

Ph(3-Me)

1.5499

TABLE 34

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

R

3

Ar

(n

D

20

)

4-29

CF

3

Pr-i

CH

2

C≡CH

Ph(4-F)

4-30

Et

Pr-i

CH

2

C≡CH

Ph(4-Cl)

4-31

CF

3

Pr-i

CH

2

C≡CH

Ph(4-Cl)

4-32

Et

Pr-i

CH

2

C≡CH

Ph

4-33

CF

3

Pr-i

CH

2

C≡CH

Ph

4-34

Et

Pr-i

CH

2

C≡CH

Ph(4-Me)

4-35

CF

3

Pr-i

CH

2

C≡CH

Ph(4-Me)

4-36

CF

2

Cl

Pr-i

Me

Ph

1.5382

4-37

CF

2

Cl

Pr-i

Me

Ph(4-F)

1.4929

4-38

Pr-i

Pr-i

Me

132-133

4-39

Pr-i

Pr-i

Me

4-40

Pr-i

Pr-i

Me

Ph(3-F)

4-41

Pr-i

Pr-i

Me

Ph(2-F)

4-42

Pr-i

Pr-i

Me

Ph(4-Me)

4-43

Pr-i

Pr-i

Me

Ph(4-CN)

4-44

Pr-i

Pr-i

Me

Ph(4-OMe)

4-45

Pr-i

Pr-i

Me

Ph(4-NO

2

)

4-46

Pr-i

Pr-i

CH

2

C≡CH

Ph(4-F)

4-47

Pr-i

Pr-i

Me

Ph(2-Me)

4-48

Pr-i

Pr-i

Me

Ph(3-Me)

4-49

Pr-i

Pr-i

CH

2

C≡CH

Ph(4-F)

4-50

Pr-i

Pr-i

CH

2

C≡CH

Ph(4-Cl)

4-51

Pr-i

Pr-i

CH

2

C≡CH

Ph

4-52

Pr-i

Pr-i

CH

2

C≡CH

Ph(4-Me)

4-53

Et

Pr-i

Me

Ph(4-CF

3

)

1.5117

4-54

Et

Et

Me

Ph(4-F)

1.5462

4-55

Et

Pr-i

Me

2-thienyl

109-110

TABLE 35

m. p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

p

Q

q

Xn

(n

D

20

)

5-1

CF

3

Pr-i

2

O

0

H

126-128

5-2

CF

3

Pr-i

2

O

0

4-F

1.5279

5-3

CF

3

Pr-i

2

O

0

4-Cl

5-4

CF

3

Pr-i

2

O

0

4-Me

5-5

CF

3

Pr-i

3

O

0

H

5-6

CF

3

Pr-i

3

O

0

4-F

5-7

CF

3

Pr-i

3

O

0

4-Cl

5-8

CF

3

Pr-i

3

O

0

4-Me

5-9

CF

3

Pr-i

2

O

1

H

93-95

5-10

CF

3

Pr-i

2

O

1

4-F

1.5090

5-11

CF

3

Pr-i

2

O

1

4-Cl

5-12

CF

3

Pr-i

2

O

1

4-Me

5-13

CF

3

Pr-i

3

O

1

H

1.5181

5-14

CF

3

Pr-i

3

O

1

4-F

5-15

CF

3

Pr-i

3

O

1

4-Cl

5-16

CF

3

Pr-i

3

O

1

4-Me

5-17

CF

3

Pr-i

3

S

0

H

5-18

CF

3

Pr-i

3

S

0

4-F

5-19

CF

3

Pr-i

3

S

0

4-Cl

5-20

CF

3

Pr-i

3

S

0

4-Me

5-21

CF

3

Pr-i

3

S

1

H

5-22

CF

3

Pr-i

3

S

1

4-F

5-23

CF

3

Pr-i

3

S

1

4-Cl

5-24

CF

3

Pr-i

3

S

1

4-Me

5-25

CF

3

Pr-i

2

S

1

H

138-140

TABLE 36

m.p. (° C.) or

refractive

Compound

index

No.

R

1

R

2

p

Q

q

Xn

(n

D

20

)

5-26

CF

3

Pr-i

2

S

1

4-F

5-27

CF

3

Pr-i

2

S

1

4-Cl

5-28

CF

3

Pr-i

2

S

1

4-Me

5-29

Et

Pr-i

3

O

0

H

5-30

Et

Pr-i

3

O

0

4-F

5-31

Et

Pr-i

3

O

0

4-Cl

5-32

Et

Pr-i

3

O

0

4-Me

5-33

Et

Pr-i

2

O

1

H

5-34

Et

Pr-i

2

O

1

4-F

5-35

Et

Pr-i

2

O

1

4-Cl

5-36

Et

Pr-i

2

O

1

4-Me

5-37

Et

Pr-i

3

O

1

H

5-38

Et

Pr-I

3

O

1

4-F

5-39

Et

Pr-i

3

O

1

4-Cl

5-40

Et

Pr-i

3

O

1

4-Me

5-41

Et

Pr-i

3

S

0

H

5-42

Et

Pr-i

3

S

0

4-F

5-43

Et

Pr-i

3

S

0

4-Cl

5-44

Et

Pr-i

3

S

0

4-Me

5-45

Et

Pr-i

3

S

1

H

5-46

Et

Pr-i

3

S

1

4-F

5-47

Et

Pr-i

3

S

1

4-Cl

5-48

Et

Pr-i

3

S

1

4-Me

TABLE 37

m. p. (° C.), refractive index

Compound

(n

D

20

) or NMR (δ(ppm),

No.

R

1

R

2

R

3

300 MHz, CDCl

3

)

6-1

Pr-i

Pr-i

Me

44-45

6-2

Pr-i

Et

Me

1.4902

6-3

Et

Pr-i

Me

0.86(3H, d); 0.99(3H, d); 1.32(3H, t);

1.65(1H, br); 1.85-1.95(1H, m);

2.23(3H, s); 2.77-2.95(2H, m);

3.58(1H, d); 8.68(1H, s); 9.02(1H, s)

6-4

Pr

Pr-i

Me

0.86(3H, d); 0.99(3H, d); 1.00(3H, t);

1.44(1H, br); 1.73-1.83(2H, m);

1.83-1.95(1H, m); 2.23(3H, s);

2.68-2.90(2H, m); 3.59(1H, d);

8.69(1H, s); 9.01(1H, s)

6-5

Pr-i

Pr

Me

1.4929

6-6

Et

Bu-t

Me

74-75

6-7

Bu-t

Et

Me

1.02(3H, t); 1.46(9H, s); 1.65-1.72(1H, m);

2.33(3H, s); 4.16(1H, t); 8.85(1H, s); 9.00(1H, s)

6-8

Pr-i

CH(OEt)

2

Me

1.4794

6-9

CH(OEt)

2

Pr-i

Me

0.85(3H, d); 0.99(3H, d); 1.24(3H, t); 1.45(1H, br);

1.95-2.04(1H, m); 2.23(1H, s);

3.53-3.66(2H, m); 3.72-4.04(2H, m);

4.03(1H, d); 5.57(1H, s); 8.87(1H, s); 9.09(1H, s)

TABLE 38

Compound

m.p. (° C.), refractive index (n

D

20

) or

No.

R

1

R

2

R

3

NMR (δ (ppm), 300 MHz, CDCl

3

)

6-10

CH(OEt)

2

Pr-n

Me

1.4811

6-11

CH(OEt)

2

Bu-t

Me

1.4781

6-12

Pr

Pr

Me

1.4978

6-13

Et

Pr

Me

6-14

Pr

Et

Me

6-15

Pr-i

CH

2

OMe

Me

1.29(3H, d), 1.29(3H, d), 2.29(3H, s),

3.39(3H, s), 3.30-3.46(2H, m), 3.30-

3.46(1H, m), 4.1(1H, dd), 8.80(1H, s),

9.07(1H, s)

6-16

CH

2

OMe

Pr-i

Me

0.83(3H, d); 1.01(3H, d); 1.89-

2.63(1H, m); 2.22(3H, s); 3.46(3H, s);

3.61(1H, d); 4.64(2H, q); 8.80(1H, s);

9.10)1H, s)

6-17

SMe

Pr-i

Me

1.5509

6-18

Pr-i

Pr-i

CH

2

C≡CH

0.86(3H, d); 1.01(3H, d); 1.88-

1.95(1H, m); 2.22(1H, t); 2.95(1H, dd);

3.38-3.48(1H, m); 3.38-3.44(1H, dd);

4.04(1H, d); 8.71(1H, s); 9.06(1H, s)

6-19

Pr-i

Et

CH

2

C≡CH

6-20

Et

Pr-i

CH

2

C≡CH

1.5185

6-21

Pr

Pr-i

CH

2

C≡CH

46-48

6-22

Pr-i

Pr

CH

2

C≡CH

0.86(3H, d); 0.93(3H, d); 1.29(3H, d);

1.29(3H, d); 1.27-1.42(2H, m); 1.55-

1.70(2H, m): 2.23(1H, t); 3.03(1H, dd);

3.40(1Hdd); 3.37-3.50(1H, m);

4.29(1H, t); 8.74(1H, s); 9.05(1H, s)

6-23

Et

Bu-t

CH

2

C═CH

0,95(9H, s); 1.33(3H, t); 2.22(1H, t);

2.88(1F, dd); 2.93(2H, q); 3.41(1H, dd);

4.11(1H, s); 8.79(1H, s); 9.02(1H, s)

TABLE 39

m. p. (° C.), refractive index

Compound

(n

D

20

) or NMR (δ(ppm),

No.

R

1

R

2

R

3

300 MHz, CDCl

3

)

6-24

Bu-t

Et

CH

2

C≡CH

6-25

Pr

Pr

CH

2

C≡CH

6-26

Et

Pr

CH

2

C≡CH

0.87(3H, t); 0.94(3H, t); 1.18-1.45(2H, m);

1.33(3H, t); 1.55-1.74(2H, m);

2.45(1H, t); 2.87(2H, q); 3.04(1H, dd);

3.43(1H, dd); 4.25(1H, t);

8.75(1H, s); 9.01(1H, s)

6-27

Pr

Et

CH

2

C≡CH

6-28

Et

CH(Me)(SMe)

N(Me)

0.89(3H, t); 0.94(3H, t); 1.47(1H, br);

1.66(3H, d); 1.68(3H, d); 1.60-1.81(2H, m);

2.05(3H, s); 2.07(3H, s); 2.29(3H, s); 2.33(3H, s);

3.77(1H, t); 3.86(1H, t); 4.33(1H, q); 4.42(1H, q);

8.71(1H, s); 8.77(1H, s); 9.08(1H, s)

6-29

Ph

Pr-i

N(Me)

1.5632

6-30

Pr-i

Me

N(Me)

1.5012

6-31

Bu-t

Me

N(Me)

72-73

6-32

Pr-i

Ph

N(Me)

1.5598

6-33

CMe(OMe)

2

Pr-i

N(Me)

75-76

6-34

Pr-i

N(Me)

79-78

6-35

Pr-i

CH═NOMe

N(Me)

1.5079

6-36

Pr-i

N(Me)

1.5089

6-37

Et

Et

N(Me)

1.5049

The compound of the present invention can be produced, for example, by the following processes, but is not restricted to such processes. Further, syntheses of intermediates will also be described.

In the formulae, R

1

, R

2

, R

7

and R

8

have the same meanings as defined above, respectively, and R

13

is a C

1

-C

6

alkyl group.

Namely, in step (1-1), 1 equivalent of a compound represented by the formula [II-1] is reacted with from 1 to 10 equivalents of a compound represented by the formula [II-2] in acetic anhydride to obtain a compound represented by the formula [II-4]. Here, from 0.01 to 1.0 equivalent of a catalyst (such as zinc chloride) may be added, as the case requires.

The reaction is carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (1-2), 1 equivalent of a compound represented by the formula [II-4] is reacted with from 1 to 10 equivalents of a Lewis acid salt of a compound represented by the formula [II-6] in the presence of from 1 to 10 equivalents of a base in an inert solvent to obtain a compound represented by the formula [II-7]. By this reaction, in some cases, a compound represented by the formula [II-8] will also be obtained as a by-product.

Here, the inert solvent may, for example, be an ether such as diethyl ether, tetrahydrofuran or dioxane, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The base may, for example, be an alkali metal such as sodium or potassium, an alkali metal alkoxide such as sodium methoxide or potassium tert-butoxide, or an alkali metal hydride such as sodium hydride or potassium hydride.

The Lewis acid may, for example, be acetic acid or hydrochloric acid.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 hour to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Further, in step (1-3), 1 equivalent of a compound represented by the formula [II-1] is reacted with from 1 to 10 equivalents of a compound represented by the formula [II-3] in an inert solvent or without using any to solvent, to obtain a compound represented by the formula [II-5].

Here, the inert solvent may, for example, be a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Further, in step (1-4), 1 equivalent of a compound represented by the formula [II-5] is reacted with from 1 to 5 equivalents of a Lewis acid salt of a compound represented by the formula [II-6] in an inert solvent in the presence of from 1 to 10 equivalents of a base to obtain a compound represented by the formula [II-7]. In this reaction, sometimes, a compound represented by the formula [II-8] will also be obtained as a by-product.

The inert solvent may, for example, be an ether such as diethyl ether, tetrahydrofuran or dioxane, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The base may, for example, be an alkali metal such as sodium or potassium, an alkali metal alkoxide such as sodium methoxide or potassium tert-butoxide, or an alkali metal hydride such as sodium hydride or potassium hydride.

The Lewis acid may, for example, be acetic acid or hydrochloric acid.

The reaction may be carried out in a nitrogen tag stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

L

1

represents a halogen atom, and R

1

, R

2

, R

7

and R

8

in the formulae, have the same meanings as defined above, respectively.

Namely, in step (2-1), 1 equivalent of a compound represented by the formula [II-7] is reduced with from 0.5 to 10 equivalents of a reducing agent (such as a borane-tert-butylamine complex or sodium borohydride) in an inert solvent to obtain a compound represented by the formula [III-3].

The inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol, tert-butyl alcohol or methyl alcohol.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In step (2-2), 1 equivalent of a compound represented by the formula [III-1] is reacted with from 1 to 10 equivalents of a compound represented by the formula [III-2] in an inert solvent in the presence of from 1 to 10 equivalents of magnesium, or an alkyl lithium such as methyl lithium, ethyl lithium or n-butylithium, to obtain a compound represented by the formula [III-3].

Here, the inert solvent may, for example, be an ether such as diethyl ether, tetrahydrofuran or dioxane, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −100° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Further, the compound represented by the formula [III-1] as the intermediate to be used in the above production process, can be synthesized, for example, by a method disclosed in e.g. the specification of international application WO97/37978.

In step (2-3), 1 equivalent of a compound represented by the formula [III-4] is reacted with from 1 to 10 equivalents of a compound represented by the formula [III-5] in an inert solvent in the presence of from 1 to 10 equivalents of magnesium or an alkyl lithium such as methyl lithium, ethyl lithium or n-butylithium, to obtain a compound represented by the formula [III-3].

Here, the inert solvent may, for example, be an ether such as diethyl ether, tetrahydrofuran or dioxane, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −100° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, L

2

represents a C

1

-C

6

alkyl group or a phenyl group which may be substituted by a C

1

-C

6

alkyl group, and R

1

, R

2

, R

3

, R

7

, R

8

and L

1

have the same meanings as defined above, respectively.

Namely, in step (3-1), 1 equivalent of a compound represented by the formula [III-3] is chlorinated with from 1 to 10 equivalents of a chlorinating agent (such as thionyl chloride or hydrogen chloride) in an inert solvent, to obtain a compound represented by the formula [IV-1].

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, tetrahydrofuran or dioxane, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In step (3-2), 1 equivalent of a compound represented by the formula [IV-1] is reacted with from 1 to 10 equivalents of a compound represented by the formula [IV-3] in an inert solvent, to obtain a compound represented by the formula [IV-4].

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, a hydrocarbon such as n-hexane, benzene, toluene or xylene, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Further, in step (3-3), 1 equivalent of a compound represented by the formula [III-3] is reacted with from 1 to 10 equivalents of a compound represented by the formula [IV-8] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain a compound represented by the formula [IV-2].

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, tetrahydrofuran or dioxane, a hydrocarbon such as n-hexane, benzene, toluene or xylene, or a pyridine such as pyridine.

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.03]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Further, in step (3-4), 1 equivalent of a compound represented by the formula [IV-2] is reacted with from 2 to 10 equivalents of a compound represented by the formula [IV-3] in an inert solvent, to obtain a compound represented by the formula [IV-4].

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine'such as pyridine, or water.

The reaction may be carried in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the ref lux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In step (3-5), 1 equivalent of a compound represented by the formula [III-3] is azidated with from 1 to 10 equivalents of an azidation agent such as tosyl azide, diphenylphospholyl azide, sodium azide, lithium azide or hydrogen azide in the presence or absence of boron trifluoridediethylether complex, triphenyl phosphine and trifluoroacetic acid in an inert solvent, to obtain a compound represented by the formula [IV-5].

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In step (3-6), 1 equivalent of a compound represented by the formula [IV-5] is treated with from 1 to 10 equivalents of reducing agent such as magnesium, lithium aluminum hydride, sodium borohydride, triphenylphosphine, or iron, or subjected to a hydrogenation catalytic reduction with a catalyst such as palladium carbon, platinum carbon or Raney Nickel, to obtain a compound represented by the formula [IV-6] in an inert solvent.

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, tetrahydrofuran or dioxane, an alcohol such as methyl alcohol or ethyl alcohol, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In step (3-7), 1 equivalent of a compound represented by the formula [IV-6] is reacted with from 1 to 10 equivalents of a compound represented by the formula [IV-7] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain a compound represented by the formula [IV-4].

Here, the inert solvent may, for example, be a halogenatedhydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, tetrahydrofuran or dioxane, an alcohol such as methyl alcohol or ethyl alcohol, a hydrocarbon such as n-hexane, benzene, toluene or xylene, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a pyridine such as pyridine, or water.

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

1

, R

2

, R

3

, R

7

, R

8

, Z and Ar have the same meanings as defined above, respectively.

Namely, in step (4-1), 1 equivalent of a compound represented by the formula [IV-4] is reacted with from 1 to 10 equivalents of a compound represented by the formula [V-1] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, or 1 equivalent of a compound represented by the formula [IV-4] is reacted with from 1 to 10 equivalents of a compound represented by the formula [V-2] in an inert solvent in the presence of from 1 to 10 equivalents of a condensing agent (such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride or 1,1′-carbonylbis-1H-imidazole), to obtain the desired compound of the present invention represented by the formula [V].

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran or dioxane, a hydrocarbon such as n-hexane, benzene, toluene or xylene, or an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide.

The base may, for example,be an inorganic base such as potassium carbonate, sodium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate, sodium hydroxide or potassium hydroxide, or an organic base such as pyridine or triethylamine.

Each reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

1

, R

2

, R

3

, R

7

, R

8

, Z and Ar have the same meanings as defined above, respectively.

Namely, in step (5-1), 1 equivalent of the compound of the present invention represented by the formula [V] is reacted with from 0.3 to 10 equivalents of diphosphorus pentasulfide or a Lawson reagent in an inert solvent, to obtain the desired compound of the present invention represented by the formula [VI].

Here, the inert solvent may, for example, be a hydrocarbon such as n-hexane, benzene, toluene or xylene, or a pyridine such as pyridine.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

1

, R

2

, R

3

, R

4

, R

5

, R

6

, R

6a

R

7

, R

8

, Ar and L

1

have the same meanings as defined above, respectively.

Namely, in step (6-1), 1 equivalent of a compound of the formula [IV-4] is reacted with from 0.5 to 5 equivalents of a compound represented by the formula [VII-1] or a compound represented by the formula [VII-2] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain the desired compound of the present invention represented by the formula [VII-3].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, tetrahydrofuran or dioxane, an alcohol such as methyl alcohol, isopropyl alcohol or ethyl alcohol, a hydrocarbon such as n-hexane, benzene, toluene or xylene, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (6-2), 1 equivalent of the compound of the present invention represented by the formula [VII-3] is reacted with from 1 to 10 equivalents of a compound represented by the formula [VII-4] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain the desired product of the present to invention represented by the formula [VII].

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, or water.

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In step (6-3), 1 equivalent of a compound represented by the formula [IV-4] is reacted with from 1 to 10 equivalents of a compound represented by the formula [VII-5] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain a compound represented by the formula [VII-6].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, tetrahydrofuran or dioxane, an alcohol such as methyl alcohol or ethyl alcohol, a hydrocarbon such as n-hexane, benzene, toluene or xylene, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (6-4), step (6-5) and step (6-6), 1 equivalent of a compound represented by the formula [VII-6] is reacted with from 1 to 10 equivalents of a compound represented by the formula [VII-7], a compound represented by the formula [VII-8] and a compound represented by the formula [VII-9] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain the compound of the present invention represented by the formula [VII], a compound represented by the formula [VII′] and a compound represented by the formula [VII″].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

1

, R

2

, R

7

, R

8

, Z and Ar have the same meanings as defined above, respectively, and R

13a

is a C

1

-C

6

alkyl group.

Namely, in step (7-1), 1 equivalent of a compound represented by the formula [VIII-1] is reacted with from 1 to 10 equivalents of paraformaldehyde in an inert solvent (depending upon the conditions, using a Dean Stark or adding a catalyst), to obtain a compound represented by the formula [VIII-2].

Here, the inert solvent may, for example, be a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The catalyst may, for example, be an organic base such as triethylamine.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (7-2), 1 equivalent of the compound represented by the formula [VIII-2] is reacted with from 1 to 10 equivalents of a compound represented by the formula [V-1] in an inert solvent, to obtain a compound represented by the formula [VIII-3].

Here, the inert solvent may, for example, be a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Further, in step (7-3), 1 equivalent of the compound of the formula [VIII-3] is reacted with from 1 to 4 equivalents of a compound represented by the formula [VIII-4] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain the compound of the present invention, represented by the formula [VIII].

Here, the inert solvent may, for example, be a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The base may, for example, be an inorganic base such as potassium carbonate, sodium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate, sodium hydroxide or potassium hydroxide, or an organic base such as pyridine or triethylamine.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

1

, R

2

, R

3

, R

7

, R

8

and Ar have the same meanings as defined above, respectively.

Namely, in step (8-1), 1 equivalent of a compound represented by the formula [IV-4] is reacted with from 1 to 10 equivalents of a compound represented by the formula [IX-1] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain the desired compound of the present invention represented by the formula [IX].

The base may, for example, be an inorganic base such as potassium carbonate, sodium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate, sodium hydroxide or potassium hydroxide, or an organic base such as pyridine or triethylamine.

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

1

, R

7

, R

8

and L

1

have the same meanings as defined above, respectively, and each of R

21

and R

22

is a hydrogen atom or a C

1

-C

6

alkyl group, R

23

is a C

1

-C

6

alkoxy group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

6

alkylthio group, a cyano group or NR

9

R

10

, and R

9

and R

10

have the same meanings as defined above, respectively.

Namely, in step (9-1), 1 equivalent of a compound represented by the formula [X-1] is halogenated with from 1 to 10 equivalents of a chlorinating agent (such as sulfuryl chloride, N-chlorosuccinimide or chlorine) in an inert solvent, to obtain a compound represented by the formula [X-2].

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as chloroform or dichloromethane, an ether such as diethyl ether, tetrahydrofuran or dioxane, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen atmosphere, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (9-2), 1 equivalent of the compound represented by the formula [X-2] is reacted with from 1 to 10 equivalents of a compound represented by the formula [X-3] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain a compound represented by the formula [x-4].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, a hydrocarbon such as n-hexane, benzene, toluene or xylene or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

2

, R

3

, R

7

, R

8

, R

9

, R

10

, W, L

1

and Ar have the same meanings as defined above, respectively, R

13b

is a C

1

-C

6

alkyl group, or a C

1

-C

4

saturated carbon chain, two of which may be bonded to each other, R

13c

is a C

1

-C

6

alkyl group, each of R

14

and R

15

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group or a C

3

-C

6

cycloalkyl group, and s is 0 or 1.

Namely, in step (10-1), 1 equivalent of a compound represented by the formula [XI-1] is reacted with from 0.9 to 20 equivalents of an acid such as hydrochloric acid or sulfuric acid in an inert solvent, to obtain the desired compound of the present invention represented by the formula [XI-2].

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, a ketone such as acetone or methyl ethyl ketone, water, or a mixed solution thereof.

The reaction may be carried out in a nitrogen stream as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (10-2), 1 equivalent of the compound of the present invention represented by the formula [XI-2] is reacted with from 1 to 10 equivalents of hydroxylamine hydrochloride in an inert solvent in the presence of sodium acetate, potassium acetate, sodium carbonate or potassium carbonate, to obtain the desired compound of the present invention represented by the formula [XI-3].

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide, or a diethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (10-3), 1 equivalent of a compound represented by the formula [XI-3] is reacted with from 1 to 10 equivalents of a dehydrating agent in an inert solvent, to obtain the compound of the present invention represented by the formula [XI-4).

The dehydrating agent may, for example, be 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride, 1,1′-carbonyldiimidazole, thionyl chloride, phosphorus pentachloride, methanesulfonyl chloride, diphosgene, p-toluene sulfonyl chloride, or acetic anhydride.

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as dichloromethane, chloroform or carbon tetrachloride, an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (10-4), 1 equivalent of the compound of the present invention represented by the formula [XI-4] is reacted with from 1 to 10 equivalents of a compound represented by the formula [XI-5] and with of from 1 to 10 equivalents of an alkyl lithium such as methyl lithium, ethyl lithium or n-butylithium, or magnesium in an inert solvent, to obtain a compound represented by the formula [XI-6].

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Here, the inert solvent may, for example be an ether such as diethyl ether, tetrahydrofuran or dioxane, a hydrocarbon such as n-hexane, benzene, toluene or xylene, or water.

Further, in step (10-5), 1 equivalent of the compound of the present invention represented by the formula [XI-9] is reacted with from 0.9 to 20 equivalents of an acid such as hydrochloric acid or sulfuric acid in an inert solvent, to obtain the desired compound of the present invention represented by the formula [XI-6].

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, a ketone such as acetone or methyl ethyl ketone, water, or a mixed solution thereof.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (10-6), 1 equivalent of the compound of the present invention represented by the formula [XI-6] is reacted with from 1 to 10 equivalents of a compound represented by the formula [XI-7] in an inert solvent in the presence of 1 to 10 equivalents of sodium acetate, potassium acetate, sodium carbonate or potassium carbonate, to obtain the desired compound of the present invention represented by the formula [XI-8].

Here, the inert solvent may, for example be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (10-7), 1 equivalent of the compound of the present invention represented by the formula [XI-2] is reacted with from 1 to 10 equivalents of an oxidizing agent such as potassium permanganate, peracetic acid, hydrogen peroxide, m-chloroperbenzoic acid or sodium hypochlorite in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base such as sodium hydroxide or potassium hydroxide, to obtain the desired compound of the present invention represented by the formula [XI-10].

Here, the inert solvent may, for example, be a ketone such as acetone or methyl ethyl ketone, an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, water or a mixed solution thereof.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (10-8), 1 equivalent of the compound of the present invention represented by the formula [XI-10] is reacted with from 1 to 50 equivalents of a compound represented by the formula [XI-11] in an inert solvent or without using any solvent in the presence of e.g. sulfuric acid or p-toluene sulfonic acid, to obtain the desired compound of the present invention represented by the formula [XI-12].

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In step (10-9), 1 equivalent of the compound of the present invention represented by the formula [XI-10] is reacted with from 1 to 10 equivalents of a chlorinating agent such as thionyl chloride in an inert solvent, to obtain a compound represented by the formula [XI-13].

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as dichloromethane, chloroform or carbon tetrachloride, an ether such as diethyl ether, tetrahydrofuran or dioxane, or a hydrocarbon such as n-hexane, benzene, toluene or xylene.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (10-10), 1 equivalent of the compound represented by the formula [XI-13] is reacted with from 1 to 3 equivalents of a compound represented by the formula [XI-11] in an inert solvent in the presence or absence of from 1 to 6 equivalents of a base, to obtain the desired compound of the present invention represented by the formula [XI-12].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Further, in step (10-11), 1 equivalent of the compound of the present invention represented by the formula [XI-10] is reacted with from 1 to 3 equivalents of a compound represented by the formula [XI-15] in an inert solvent in the presence or absence of from 1 to 6 equivalents of a base by using a peptidizing agent such as 1,1′-carbonylbis-1H-imidazole or N,N′-dicyclohexylcarbodiimide, to obtain the desired compound of the present invention represented by the formula [XI-14].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as dichloromethane, chloroform or carbon tetrachloride, an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In step (10-12), 1 equivalent of the compound represented by the formula [XI-13] is reacted with from 1 to 3 equivalents of a compound represented by the formula [XI-15] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain the desired compound of the present invention represented by the formula [XI-14].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from room temperature to the reflux temperature in the reaction system and will be completed in from 1 to 100 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

1

, R

2

, R

7

, R

8

, Q and Ar have the same meanings as defined above, respectively, Ms is a methanesulfonyl group, p is 2, 3 or 4, and q is 1 or 0.

Namely, in steps (11-1) and (11-2), 1 equivalent of a compound represented by the formula [IV-1] or a compound represented by the formula [IV-2] is reacted with from 0.9 to 3 equivalents of a compound represented by the formula [XII-1] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain a compound represented by the formula [XII-2].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (11-3), 1 equivalent of the compound represented by the formula [XII-2] is reacted with from 1 to 10 equivalents of phosgene or thiophosgene in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain the desired compound of the present invention, as represented by the formula [XII].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the inert solvent may, for example, be an ether such as diethyl ether, tetrahydrofuran or dioxane, a halogenated hydrocarbon such as dichloromethane, chloroform or carbon tetrachloride, a hydrocarbon such as n-hexane, benzene, toluene or xylene, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

In the formulae, R

1a

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a C

3

-C

6

cycloalkyl group, a phenyl group or a C

1

-C

4

haloalkyl group, R

16

is a hydrogen atom, a C

1

-C

6

alkyl group, a C

2

-C

6

alkenyl group, a C

2

-C

6

alkynyl group, a C

1

-C

6

alkoxy C

1

-C

6

alkyl group, a C

3

-C

6

cycloalkyl group or a phenyl group, Y is an oxygen atom, a sulfur atom or NR

9

, R

9

has the same meaning as defined above, and r is 1 or 2.

Namely, in step (12-1), 1 equivalent of a compound represented by the formula [XIII-1] is reacted with from 1 to 10 equivalents of N-methylformanilide or N,N-dimethylformamide and from 1 to 20 equivalents of phosphorusoxychloride in an inert solvent or without using any solvent, to obtain a compound represented by the formula [XIII-2].

Here, the inert solvent may, for example, be an ether such as diethyl ether, tetrahydrofuran or dioxane, a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, chlorobenzene or dichlorobenzene, a hydrocarbon such as n-hexane, benzene, toluene or xylene, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it depends upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (12-2), 1 equivalent of the compound represented by the formula [XIII-2] is reacted with from 1 to 3 equivalents of a compound represented by the formula [XIII-3] in an inert solvent in the presence or absence of from 1 to 10 equivalents of a base, to obtain a compound represented by the formula [XIII-4].

The base may, for example, be sodium hydride, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium methoxide or potassium tert-butoxide.

Here, the solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −100C to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Further, in step (12-3), 1 equivalent of the compound represented by the formula [XIII-2] is subjected to hydrogenation and reacted in an inert solvent by using from 1 to 8 equivalents of manganese oxide and from 0.01 to 4 equivalents of a catalyst such as palladium carbon or Raney Nickel, to obtain a compound represented by the formula [XIII-5].

Here, the inert solvent may, for example, be an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine or water.

The reaction is carried out at an optional temperature from −10° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Then, in step (12-4), 1 equivalent of the compound represented by the formula [XIII-5] is subjected to an oxidation reaction in an inert solvent by using from 1 to 10 equivalents of oxalyl chloride, from 1 to 10 equivalents of dimethylsulfoxide and from 1 to 10 equivalents of triethylamine or the like, to obtain a compound represented by the formula [XIII-63].

Here, the inert solvent may, for example, be a halogenated hydrocarbon such as dichloromethane, chloroform or carbon tetrachloride, an alcohol such as ethyl alcohol, isopropyl alcohol or methyl alcohol, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aprotic polar solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulfoxide, a hydrocarbon such as n-hexane, benzene, toluene or xylene, a pyridine such as pyridine, or water.

The reaction may be carried out in a nitrogen stream, as the case requires. The reaction is carried out at an optional temperature from −80° C. to the reflux temperature in the reaction system and will be completed in from 1 to 24 hours, although it varies depending upon the compound. The desired product can be isolated from the reaction solution by a usual method and may be purified by distillation or column chromatography, as the case requires.

Now, the processes for production, a formulation method and the application of the compound of the present invention will be described in detail with reference to Examples. Further, the processes for production of intermediates in the synthesis of the compound of the present invention will also be described.

PREPARATION EXAMPLE 1

Preparation of N-methyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]phenylacetamide (Compound No. 1-8 of the Present Invention)

6 g (26 mmol) of 4-trifluoromethyl-5-[1-(N-methylamino)-2-methylpropyl]pyrimidine and 3.6 g (26 mmol) of potassium carbonate were dissolved in 150 ml of acetonitrile, and 4 g (26 mmol) of phenylacetyl chloride was dropwise added, followed by stirring at room temperature for 3 hours. To the reaction solution, 200 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the obtained crude crystals were washed with n-hexane to obtain 7.7 g (yield: 85%) of N-methyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]phenylacetamide as colorless transparent crystals (melting point: 106-109° C.).

PREPARATION EXAMPLE 2

Preparation of N-methyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]-2-pyridylacetamide (Compound No. 2-3 of the Present Invention)

0.3 g (1.7 mmol) of 2-pyrimidinylacetate hydrochloride and 0.18 g (1.8 mmol) of triethylamine were dissolved in 30 ml of tetrahydrofuran, and 0.28 g (1.7 mmol) of 1,1′-carbonylbis-1H-imidazole was added, followed by stirring at room temperature for 1 hour. Then, 0.4 g (1.7 mmol) of 4-trifluoromethyl-5-[1-(N-methylamino)-2-methylpropyl]pyrimidine was added, followed by heating and refluxing for further 3 hours. To the reaction solution, 100 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate:methanol=4.5:4.5:1) to obtain 0.2 g (yield: 33%) of N-methyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]-2-pyridylacetamide as colorless transparent crystals (melting point: 99-100° C.).

PREPARATION EXAMPLE 3

Preparation of N-methyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]phenylthioacetamide (Compound No. 1-142 of the Present Invention)

0.45 g (1.3 mmol) of N-methyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]phenylthioacetamide and 0.52 g (1.3 mmol) of a Lawson reagent were dissolved in 30 ml of toluene, followed by heating and refluxing for 30 hours. To the reaction solution, 100 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried with anhydrous magnesium sulfate. Ethyl acetate m was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=3:1) to obtain 0.12 g (yield: 26%) of N-methyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]phenylthioacetamide as slightly yellow crystals (melting point: 93-94° C.).

PREPARATION EXAMPLE 4

Preparation of N-methoxymethyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]-4-chlorophenylacetamide (Compound No. 1-105 of the Present Invention)

1.0 g (4.6 mmol) of 4-trifluoromethyl-5-[1-amino-2-methylpropyl]pyrimidine, 0.23 g (6.9 mmol)of paraformaldehyde and 0.1 g (9.9 mmol) of triethylamine were dissolved in 50 ml of toluene. Heating and refluxing were carried out for 1 hour while removing water from the reaction system by means of Dean's Stark. The reaction solution was returned to room temperature, and 0.86 g (4.6 mmol) of 4-chlorophenylacetylchloride was dropwise added, followed by stirring for further 2 hours. To this solution, 10 ml of a toluene solution containing 0.2 g (6.2 mmol) of methanol and 0.5 g (4.9 mmol) of triethylamine, was dropwise added, followed by stirring at room temperature for 1 hour. To the reaction solution, 100 mg of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=3:1) to obtain 0.5 g (yield: 26%) of N-methoxymethyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]-4-chlorophenylacetamide as colorless transparent crystals (melting point: 142-145° C.).

PREPARATION EXAMPLE 5

Preparation of N-methyl-N-[2-methyl-1-(4-chlorodifluoromethylpyrimidin-5-yl)propyl]-N′-(4-methylphenyl)urea (Compound No. 1-37 of the Present Invention)

0.50 g (2.1 mmol) of 4-chlorodifluoromethyl-5-[1-(N-methylamino)-2-methylpropyllpyrimidine and 0.28 g (2.1 mmol) of 4-methylphenyl isocyanate were dissolved in 30 ml of isopropyl ether, followed by stirring at room temperature for 1 hour. Precipitated crystals were collected by filtration to obtain 0.65 g (yield: 84%) of N-methyl-N-[2-methyl-1-(4-chlorodifluoromethylpyrimidin-5-yl)propyl]-N′-(4-methylphenyl)urea as colorless transparent crystals (melting point: 135-137° C.).

PREPARATION EXAMPLE 6

Preparation of 1,3-dimethyl-1-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-3-phenylurea (Compound No. 1-424 of the Present Invention)

0.8 g (3.4 mmol) of 4-trifluoromethyl-5-[1-(N-methylamino)-2-methylpropyl]pyridine was dissolved in 30 ml of chloroform, and 5 mg of a chloroform solution of 0.45 g (3.8 mmol) of phenyl isocyanate was dropwise added, followed by stirring at room temperature for 10 hours. To the reaction solution, 50 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the obtained crude crystals were washed with n-hexane to obtain 1.0 g (yield: 83%) of 1-methyl-1-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-3-phenylurea. 0.5 g (1.4 mmol) of the obtained 1-methyl-1-(2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl)-3-phenylurea was dissolved in 30 mg of tetrahydrofuran, and 0.06 g (2.5 mmol) of sodium hydride was added, followed by stirring at room temperature for 0.5 hour. Then, 0.22 g (1.6 mmol) of methyl iodide was dropwise added, followed by stirring at room temperature for 4 hours. To the reaction solution, 50 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the obtained crude product was purified by silica gel chromatography (developing solvent/n-hexane:ethyl acetate 9:1 to 3:1) to obtain 0.28 g (yield: 53.8%) of 1,3-dimethyl-1-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl-3-phenylurea as colorless crystals (melting point: 104-105° C.).

PREPARATION EXAMPLE 7

Preparation of N-[1-(4-ethyl-pyrimidin-5-yl)-2-methylpropyl]-4-fluoro-N-methyl-benzenesulfonamide (Compound No. 4-3 of the Present Invention)

0.4 g (0.2 mmol) of [1-(4-ethyl-pyrimidin-5-yl)-propyl]-methyl-amine was dissolved in 20 ml of pyridine, and 0.43 g (0.22 mmol) of p-fluorobenzenesulfonyl chloride was dropwise added, followed by stirring at room temperature for 10 hours. To the reaction solution, 50 ml of water was added, followed by extraction with diethyl ether. The obtained organic phase was washed twice with 30 ml of a dilute citric acid aqueous solution and then dried over anhydrous magnesium sulfate. Diethyl ether was distilled off under reduced pressure, and the obtained crude product was purified by silica gel chromatography (developing solvent/n-hexane:ethyl acetate 4:1 to 1:1) to obtain 0.4 g (yield: 56%) of (N-[1-(4-ethyl-pyrimidin-5-yl)-2-methylpropyl]-4-fluoro-N-methyl-benzenesulfonamide as a colorless oil (n

D

20

=1.5399).

PREPARATION EXAMPLE 8

Preparation of 1-(4-chlorobenzyl)-1,3-dimethyl-3-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-urea (Compound No. 1-532 of the Present Invention)

0.16 g (1.0 mmol) of (4-chlorobenzyl)-methylamine was dissolved in 30 ml of pyridine, and 0.3 g (1.0 mmol) of N-methyl-N-(2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-carbamoyl chloride was dropwise added, followed by stirring at room temperature for 10 hours. To the reaction solution, 50 ml of water was added, followed by extraction with diethyl ether. The obtained organic phase was washed twice with 30 ml of a dilute citric acid aqueous solution, followed by drying over anhydrous magnesium sulfate. Diethyl ether was distilled off under reduced pressure, and the obtained crude product was purified by silica gel chromatography (developing solvent/n-hexane:ethyl acetate=8:1 to 3:1) to obtain 0.22 g (yield: 52%) of 1-(4-chlorobenzyl)-1,3-dimethyl-3-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-urea as colorless crystals (melting point: 95-98° C.).

PREPARATION EXAMPLE 9

Preparation of N-[1-(4-diethoxymethylpyrimidin-5-yl)-2-methylpropyl]-N-methyl-2-phenyl acetamide (Compound No. 1-453 of the Present Invention)

8.3 g (0.031 mol) of [1-(4-diethoxymethylpyrimidin-5-yl)-2-methylpropyl]methylamine and 6.4 g (46 mmol) of potassium carbonate were added to 100 ml of acetonitrile, and then 5.8 g (0.038 mol) of phenylacetyl chloride was dropwise added at room temperature and reacted for 2 hours. After completion of the reaction, the product was poured into water and extracted with ethyl acetate. The organic layer was washed with an aqueous citric acid solution, water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained oily product was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:5 to ethyl acetate), to obtain 8.4 g (yield: 70%) of N-[1-(4-diethoxymethylpyrimidin-5-yl)-2-methylpropyl]-N-methyl-2-phenyl acetamide as colorless viscous liquid (n

D

2

=1.5253)

PREPARATION EXAMPLE 10

Preparation of N-[1-(4-formylpyrimidin-5-yl)-2-methylpropyll-N-methyl-4-fluorophenylacetamide (Compound No. 1-523 of the Present Invention)

8.4 g (2.1 mmol) of N-[1-(4-diethoxymethylpyrimidin-5-yl)-2-methylpropyl]-N-methy4-fluorophenylacetamide was dissolved in 100 ml of acetone, and 13 ml of 6N hydrochloric acid was added and reacted at room temperature for 5 hours. After completion of the reaction, the reaction solution was concentrated, and an aqueous sodium hydrogencarbonate solution was added to alkaline, followed by extraction with ethyl acetate. The organic layer was washed with an aqueous citric acid solution, water and an aqueous sodium chloride solution, in this order, dried and concentrated, and the obtained oily product was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:5 to ethyl acetate) to obtain 5.3 g (yield: 77%) of N-[1-(4-formylpyrimidin-5-yl)-2-methylpropyl]-N-methyl-4-fluorophenylacetamide as colorless viscous liquid (n

D

20

=1.5466).

PREPARATION EXAMPLE 11

Preparation of N-[1-(4-hydroxyiminomethylpyrimidin-5-yl)-2-methylpropyl]-N-methylphenylacetamide (Compound No. 1-500 of the Present Invention)

1.0 g (3.2 mmol) of N-(1-(4-formylpyrimidin-5-yl)-2-methylpropyl]-N-methylphenylacetamide was dissolved in 30 ml of methanol, and 0.45 g (6.5 mmol) of hydroxylamine hydrochloride and 0.63 g (6.4 mmol) of potassium acetate were added and reacted at room temperature for 1 hour. After completion of the reaction, the product was poured into water and extracted with ethyl acetate. The organic layer was washed with an aqueous sodium hydrogencarbonate solution, an aqueous citric acid solution, water and an aqueous sodium chloride solution, in this order, dried and concentrated, and the obtained oily product was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1 to ethyl acetate) to obtain 0.45 g (yield: 43%) of N-[1-(4-hydroxyiminomethylpyrimidin-5-yl)-2-methylpropyl]-N-methylphenylacetamide as colorless crystals (melting point: 171-172° C.).

PREPARATION EXAMPLE 12

Preparation of N-[1-(4-cyanopyrimidin-5-yl)-2-methylpropyl]-N-methylphenylacetamide (Compound No. 1-504 of the Present Invention)

0.25 g (0.77 mmol) of N-[1-(4-hydroxyiminomethylpyrimidin-5-yl)-2-methylpropyl]-N-methylphenylacetamide was dissolved in 30 ml of chloroform, and 0.16 g (0.83 mmol) of 1-(3-(dimethylamino)propyl]-3-ethylcarbodilmide hydrochloride was added and reacted at room temperature for 8 hours. After completion of the reaction, the solvent was distilled off, and water was added, followed by extraction with ethyl acetate. The organic layer was washed with water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained oily product was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1 to ethyl acetate) to obtain 0.19 g (yield: 88%) of N-[1-(4-cyanopyrimidin-5-yl)-2-methylpropyl]-N-methylphenylacetamide as colorless crystals (melting point: 80-81° C.).

PREPARATION EXAMPLE 13

Preparation of 2-(4-chlorophenyl)-N-[1-(4,6-dimethoxypyrimidin-5-yl)-2-methylpropyl]-N-methyl acetamide (Compound No. 3-41 of the Present Invention)

0.80 g (3.8 mmol) of 1-(4,6-dimethoxypyrimidin-5-yl)-2-methylpropylamine, 0.59 g (4.2 mmol) of methyl iodide and 0.46 g (4.6 mmol) of triethylamine were added to 10 ml of N,N-dimethylacetamide and reacted at 80° C. for 1 hour. After completion of the reaction, the product was poured into water and extracted with toluene. The organic layer was washed with water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained oily product was supplied to the subsequent reaction without purification. 0.20 g (0.89 mmol) of this oily product and 0.22 g (1.6 mmol) of potassium carbonate were added to 20 ml of acetonitrile, and then 0.30 g (1.6 mmol) of 4-chlorophenylacetyl chloride was added at room temperature and reacted overnight. After completion of the reaction, the product was poured into water and extracted with ethyl acetate. The organic layer was washed with an aqueous citric acid solution, water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained oily product was purified by preparative HPLC (ethyl acetate:n-hexane=1:1) to obtain 0.21 g (yield: 15%, 2 steps) of 2-(4-chlorophenyl)-N-[1(4,6-dimethoxypyrimidin-5-yl)-2-methylpropyl]-N-methyl acetamide as colorless crystals (melting point: 107-109° C.).

PREPARATION EXAMPLE 14

Preparation of 1-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-3-phenylimidazolin-2-one (Compound No. 5-1 of the Present Invention)

1.05 g (4.2 mol) of 5-(1-chloro-2-methylpropyl)-4-trifluoromethylpyrimidine and 0.61 (4.2 mol) of N-phenylethylenediamine were added to 10 ml of isopropyl alcohol, followed by stirring at room temperature for 6 hours. After completion of the reaction, the reaction solution was concentrated, then poured into water and extracted with ethyl acetate, and purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1 to ethyl acetate) to obtain 0.38 g of N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)-propyl]-N′-phenylethane-1,2-diamine. Then, 0.38 g (1 mmol) of N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)-propyl]-N′-phenylethane-1,2-diamine and 0.5 g (5 mmol) of triethylamine were added to 10 ml of dichloromethane, and a dichloromethane solution containing 0.2 g (2 mmol) of phosgene was dropwise added under cooling with ice. After the dropwise addition, stirring was further continued at room temperature for 1 hour to terminate the reaction. After termination of the reaction, the product was poured into water, washed with an aqueous sodium hydrogencarbonate solution, dried and concentrated, and the obtained oily product was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1 to ethyl acetate) to obtain 0.25 g (yield: 61%) of 1-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-3-phenylimidazolin-2-one as colorless crystals (melting point: 126-128° C.).

PREPARATION EXAMPLE 15

Preparation of 5-(1-{[2-(4-chlorophenyl)-propionyl]methylamino}-2-methylpropyl)-pyrimidine-4-carboxylic acid (Compound No. 1-718 of the Present Invention)

A solution comprising 1.0 g (3.2 mmol) of N-[1-(4-formylpyrimidin-5-yl)-2-methylpropyl]-N-methylphenylacetamide and 10 ml of tetrahydrofuran, was added to a solution comprising 0.23 g (4.1 mmol) of potassium hydroxide and 10 ml of water. Then, 0.88 g (5.56 mmol) of potassium permanganate was further added. Then, the mixture was heated at 80° C. for 3 hours. After completion of the reaction, sodium sulfite was added, followed by filtration. The filtrate was acidified with hydrochloric acid and then extracted with ethyl acetate, and the extract was washed with an aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated to obtain a crude product. This crude product was dissolved in a mixed solution of toluene, ether and acetone, followed by extraction with an aqueous potassium hydroxide solution. Then, extract was acidified with diluted hydrochloric acid and extracted with ethyl acetate. The extract was dried over magnesium sulfate, concentrated and further washed with isopropyl ether to obtain 0.33 g (yield: 32%) of 5-(1-{[2-(4-chlorophenyl)-propionyl]methylamino}-2-methylpropyl)-pyrimidine-4-carboxylic acid (diastereomer A-isomer) as slightly blown crystals (melting point: 168-170° C.).

PREPARATION EXAMPLE 16

Preparation of 5-(1-{[2-(4-chlorophenyl)-propionyl]methylamino}-2-methylpropyl)-pyrimidine-4-carboxylic acid methyl ester (diastereomer A-isomer) (Compound No. 1-592 of the Present Invention)

A few drops of concentrated sulfuric acid were added to a methanol solution of 2.00 g (5.32 mmol) of 5-(1-{[2-(4-chlorophenyl)-propionyl]methylamino}-2-methylpropyl)-pyrimidine-4-carboxylic acid, followed by heating and refluxing for 5 hours. After completion of the reaction, water was added, followed by extraction with ethyl acetate, and the extract was washed with an aqueous sodium chloride solution, dried over magnesium sulfate and concentrated, and the obtained oily product was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1 to ethyl acetate) to obtain 0.59 g (yield: 28%) of 5-(1-{[2-(4-chlorophenyl)-propionyl]methylamino}-2-methylpropyl)-pyrimidine-4-carboxylic acid methyl ester (diastereomer A-isomer) as colorless oily product.

Examples for Preparation of Intermediates

REFERENCE EXAMPLE 1

Preparation of 3-ethoxymethylene-1,1,1-trifluoro-5-methyl-2,4-hexanedione

A mixture comprising 213 g (1.17 mol) of 1,1,1-trifluoro-5-methyl-2,4-hexanedione, 242 g (1.64 mol) of ethyl orthoformate and 166 g (1.63 mol) of acetic anhydride, was heated and refluxed for 6 hours. The solvent was distilled off under reduced pressure to obtain 146 g (yield: 67%) of 3-ethoxymethylene-1,1,1-trifluoro-5-methyl-2,4-hexanedione.

REFERENCE EXAMPLE 2

Preparation of 5-isopropylcarbonyl-4-trifluoromethylpyrimidine

46 g (0.85 mol) of sodium methoxide was dissolved in 700 ml of methanol, and 76 g (0.73 mol) of formamidine acetate was added, followed by stirring at room temperature for 15 minutes. Then, 146 g (0.61 mol) of 3-ethoxymethylene-1,1,1-trifluoro-5-methyl-2,4-hexanedione was added under cooling with ice, followed by heating and refluxing for further 2 hours. The solvent was distilled off under reduced pressure, and 1,000 ml of ice water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=6:1) to obtain 89 g (yield: 67%) of 5-isopropylcarbonyl-4-trifluoromethylpyrimidine as slightly yellow liquid.

REFERENCE EXAMPLE 3

Preparation of 5-(1-hydroxy-2-methylpropyl)-4-trifluoromethylpyrimidine

25 g (115 mmol) of 5-isopropylcarbonyl-4-trifluorometylpyrimidine was dissolved in 100 ml of ethanol, and under cooling with ice, 6 g (69 mmol) of a borane-tert-butylamine complex was added, followed by stirring for 2 hours. Further, 20 ml of acetone was added, followed by stirring for 0.5 hour. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=1:1) to obtain 22 g (yield: 87%) of 5-(1-hydroxy-2-methylpropyl)-4-trifluoromethylpyrimidine as slightly yellow liquid (n

D

20

=1.4481)

REFERENCE EXAMPLE 4

Preparation of 5-(1-chloro-2-methylpropyl)-4-trifluoromethylpyrimidine

22 g (100 mmol) of 5-(1-hydroxy-2-methylpropyl)-4-trifluoromethylpyrimidine was dissolved in 150 ml of chloroform, and 25 ml (342 mmol) of thionyl chloride was added. The reaction mixture was heated and refluxed for 2 hours. The solvent and thionyl chloride was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=6:1) to obtain 11.6 g (yield: 49%) of 5-(1-chloro-2-methylpropyl)-4-trifluoromethylpyrimidine as brown liquid (refractive index n

D

20

: 1.4558).

REFERENCE EXAMPLE 5

Preparation of 5-[1-(N-methylamino)-2-methylpropyl]-4-trifluoromethylpyrimidine

4.5 g (19 mmol) of 5-(1-chloro-2-methylpropyl)-4-trifluoromethylpyrimidine was dissolved in 50 ml of isopropyl alcohol, and 10 ml (161 mmol) of a 50% methylamine aqueous solution was added, followed by stirring at room temperature for 8 hours. The solvent was distilled off under reduced pressure, and 100 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure to obtain 3.4 g (yield: 77%) of 5-(1-(N-methylamino)-2-methylpropyl]-4-trifluoromethylpyrimidine as slightly yellow liquid (refractive index n

D

20

: 1.4529).

REFERENCE EXAMPLE 6

Preparation of 4-ethoxymethylene-2,6-dimethyl-3,5-heptanedione

A mixture comprising 17.2 g (110 mmol) of 2,6-dimethyl-3,5-heptanedione, 22.8 g (153 mmol) of ethyl orthoformate and 31.5 g (309 mmol) of acetic anhydride, was reacted for 2 hours at 110° C. The solvent was distilled off under reduced pressure to obtain 11.5 g (yield: 49%) of 4-ethoxymethylene-2,6-dimethyl-3,5-heptanedione.

REFERENCE EXAMPLE 7

Preparation of 5-isopropylcarbonyl-4-isopropylpyrimidine

11.5 g (60 mmol) of a 28% sodium methoxide solution was dissolved in 100 ml of methanol, and 5.6 g (54 mmol) of formamidine acetate was added, followed by stirring at room temperature for 15 minutes. Then, 11.5 g (54 mmol) of 4-ethoxymethylene-2,6-dimethyl-3,5-heptanedione was added under cooling with ice. The reaction mixture was further reacted at 50° C. for one hour. The solvent was distilled off under reduced pressure, and 200 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=4:1) to obtain 9.2 g (yield: 89%) of 5-isopropylcarbonyl-4-isopropylpyrimidine as slightly yellow liquid.

REFERENCE EXAMPLE 8

Preparation of 5-(1-hydroxy-2-methylpropyl)-4-isopropylpyrimidine

9.2 g (48 mmol) of 5-isopropylcarbonyl-4-isopropylpyrimidine was dissolved in 50 ml of ethanol, and under cooling with ice, 2.5 g (29 mmol) of a borane-tert-butylamine complex was added, followed by stirring for 2 hours. Further, 20 ml of acetone was added, followed by stirring for 0.5 hour. The solvent was distilled off under reduced pressure, and 200 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure to obtain 8.3 g (yield: 89%) of the desired product i.e. 5-(1-hydroxy-2-methylpropyl)-4-isopropylpyrimidine.

REFERENCE EXAMPLE 9

Preparation of 5-(1-methylsulfonyloxy-2-methylpropyl)-4-isopropylpyrimidine

8.3 g (43 mmol) of 5-(1-hydroxy-2-methylpropyl)-4-isopropylpyrimidine was dissolved in 10 ml of pyridine, and under cooling with ice, 9.8 g (86 mmol) of methylsulfonyl chloride was dropwise added. The reaction mixture was reacted at room temperature for 2 hours, and then, 100 ml of ice water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with an aqueous citric acid solution and water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure to obtain 10.6 g (yield: 90%) of 5-(1-methylsulfonyloxy-2-methylpropyl)-4-isopropylpyrimidine.

[

1

H-NMR (300 MHz CDCl

3

, TMS δ (ppm)) 0.91 (3 H, d), 1.14 (3H, d), 1.31 (3H, dd), 2.1-2.2 (1H, m), 2.89 (3H, s), 3.2-3.3 (3H, m) 5.56 (1H, d), 8.68 (1H, s), 9.14 (1H, s)],

REFERENCE EXAMPLE 10

Preparation of 5-[1-(N-methylamino)-2-methylpropyl]-4-isopropylpyrimidine

10.6 g (39 mmol) of 5-(1-methylsulfonyloxy-2-methylpropyl)-4-isopropylpyrimidine was dissolved in 50 ml of isopropyl alcohol, and 10 ml (129 mmol) of a 40% methylamine aqueous solution was added, followed by stirring at room temperature for 8 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and 100 ml of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent=ethyl acetate) to obtain 2.9 g (yield: 36%) of 5-[1-(N-methylamino)-2-methylpropyl]-4-isopropylpyrimidine as slightly yellow crystals (melting point: 37-39° C.).

REFERENCE EXAMPLE 11

Preparation of 5-(1-hydroxy-2-methylpropyl)-4-methylthiopyrimidine

10.6 g (52 mmol) of 5-bromo-4-methylthiopyrimidine was dissolved in 100 ml of tetrahydrofuran, and at −60° C., 36 ml of a n-butylithium hexane solution (1.6 mol/l) was dropwise added. After stirring at −60° C. for 30 minutes, 4.1 g (57 mmol) of isobutylaldehyde was dropwise added and further reacted for 1 hour. The reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=3:2) to obtain 2.9 g (yield: 28%) of 5-(1-hydroxy-2-methylpropyl)-4-methylthiopyrimidine as slightly yellow crystals (melting point: 123-127° C.).

REFERENCE EXAMPLE 12

Preparation of 2-bromo-1-(4-ethylpyrimidin-5-yl)-propan-1-one

49.2 g (0.30 mol) of 1-(4-ethylpyrimidin-5-yl)propan-1-one was dissolved in 500 ml of carbon tetrachloride, and 53 g (0.30 mol) of N-bromosuccinimide and 0.3 g of azoisobutyronitrile were added, followed by refluxing for 2 hours. After cooling, crystals were removed by filtration, and the filtrate was concentrated and the obtained oily product was purified by column chromatography (ethyl acetate:n-hexane=1:4 to 1:2) to obtain 64.3 g (yield: 89%) of 2-bromo-1-(4-ethylpyrimidin-5-yl)-propan-1-one as yellow liquid.

REFERENCE EXAMPLE 13

Preparation of 1-(4-ethylpyrimidin-5-yl)-2-methylthio-propan-1-one

10.0 g (0.041 mol) of 2-bromo-1-(4-ethylpyrimidin-5-yl)propan-1-one was dissolved in 40 ml of isopropyl alcohol, and 21 g (0.045 mol) of a 15% sodium methythiolate aqueous solution was added under cooling with ice and then reacted at room temperature for 1 hour. After completion of the reaction, the product was poured into water and extracted with ethyl acetate. The organic layer was washed with an aqueous sodium chloride solution, dried and concentrated to obtain 9.5 g of crude 1-(4-ethylpyrimidin-5-yl)-2-methylthio-propan-1-one. The product was used for the subsequent reaction without purification.

REFERENCE EXAMPLE 14

Preparation of 4,6-dichloropyrimidine-5-carboaldehyde

To 65.0 g (0.89 mol) of N,N-dimethylformamide, 356 g (2.3 mol) of phosphorus oxychloride was added at a temperature of at most 20° C. under cooling with ice, followed by stirring at room temperature for 10 minutes. 50.0 g (0.45 mol) of 4,6-dihydroxypyrimidine was slowly added under cooling with ice. After completion of the addition, when the temperature-rising was terminated, the mixture was reacted at 90° C. for 3 hours. Excess phosphorus oxychloride was distilled off under reduced pressure, and 300 ml of chloroform was added, and the mixture was slowly added into ice water. The organic layer was washed with an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained crude crystals were washed with n-hexane to obtain 43.8 g (yield: 55%) of 4,6-dichloropyrimidine-5-carboaldehyde as brown crystals (melting point: 65-66° C.).

REFERENCE EXAMPLE 15

Preparation of 4,6-dimethoxypyrimidine-5-carboaldehyde

43.6 g (246 mmol) of 4,6-dichloropyrimidine-5-carboaldehyde was dissolved in 200 ml of methanol, and 120 g (622 mmol) of 28% sodium methoxide was added under cooling with ice and then reacted for 2 hours at room temperature. After completion of the reaction, the solvent was distilled off, and an aqueous citric acid solution was added, followed by extraction with ethyl acetate. The organic layer was washed with an aqueous sodium hydrogencarbonate solution, an aqueous citric acid solution, water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained crude crystals were washed with isopropyl ether to obtain 8.3 g (yield: 20%) of 4,6-dimethoxypyrimidine-5-carboaldehyde.

REFERENCE EXAMPLE 16

Preparation of 1-(4,6-dimethoxypyrimidin-5-yl)-3-methylbutan-2-ol

0.81 g (33 mmol) of magnesium was added to 30 ml of tetrahydrofuran, and 4.1 g (33 mmol) of 2-bromopropane was added to prepare a tetrahydrofuran solution of isopropyl magnesium bromide. 2.8 g (17 mmol) of 4,6-dimethoxypyrimidine-5-carboaldehyde was dissolved in 50 ml of tetrahydrofuran, and the solution was added to the above tetrahydrofuran solution at room temperature and reacted overnight. The reaction solution was poured into an aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with an aqueous citric acid solution, water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained oily product was purified by column chromatography (ethyl acetate:n-hexane=1:4) to obtain 1.9 g (yield: 54%) of 1-(4,6-dimethoxy pyrimidin-5-yl)-3-methylbutan-2-ol as slightly yellow crystals.

REFERENCE EXAMPLE 17

Preparation of 5-(2-azide-3-methylbutyl)-4,6-dimethoxypyrimidine

1.05 g (5 mmol) of 1-(4,6-dimethoxypyrimidin-5-yl)-3-methylbutan-2-ol was dissolved in 10 ml of toluene, and under cooling with ice, 1.01 g (10 mmol) of trimethylsilylazide and 1.42 g (10 mmol) of boron trifluoride diethyl ether complex were added sequentially and then reacted for 7 hours at room temperature. After completion of the reaction, the product was poured into water and extracted with toluene. The organic layer was washed with an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained oily product was purified by column chromatography (ethyl actate:n-hexane=1:9) to obtain 1.22 g (yield: 100%) of 5-(2-azide-3-methylbutyl)-4,6-dimethoxypyrimidine as colorless liquid.

[

1

H-NMR (300 MHz CDCl

3

, TMS δ (ppm)) 0.70 (3 H, d), 1.13 (3H, d), 2.44 (1H, m), 4.00 (6H, s), 4.38 (1H, d), 8.39 (1H, s)].

REFERENCE EXAMPLE 18

Preparation of 1-(4,6-dimethoxypyrimidin-5-yl)-2-methylpropylamine

1.2 g (5.1 mmol) of 5-(2-azide-3-methylbutyl)-4,6-dimethoxypyrimidine was dissolved in 20 ml of methanol, and under cooling with ice, 1.5 g (0.062 mol) of magnesium was added and reacted overnight. After completion of the reaction, the solvent was distilled off, and ether was added. Insolubles were filtered off, followed by extraction with diluted hydrochloric acid. An aqueous sodium hydroxide solution was added to alkaline, followed by extraction with toluene. The organic layer was washed with water and an aqueous sodium chloride solution in this order, dried and concentrated, and the obtained oily product was purified by column chromatography (ethyl acetate:n-hexane=1:1) to obtain 0.80 g (yield: 75%) of 1-(4,6-dimethoxypyrimidin-5-yl)-2-methylpropylamine as colorless crystals.

[

1

H-NMR (300 MHz, CDCl

3

, TMS δ (ppm)) 0.70 (3 H, d), 1.07 (3H, d), 1.71 (2H, s), 2.02 (1H, m), 3.78 (1H, d), 3.97 (6H, s), 8.33 (1H, s)].

Now, the physical properties (

1

H-NMR values (CDCl

3

/TMS δ (ppm)) of the compounds of the present invention prepared in accordance with the methods disclosed in processes 1 to 12, will be shown in Tables 40 to 43.

TABLE 40

Compound

No.

NMR (δ(ppm), 300MHz, TMS-CDCl

3

)

1-016

0.81(3H, d), 1.01(3H, d), 2.75-2.87(1

H, m), 2.90(1H, s), 3.60(2H, dd), 3.78(3

H, s), 5.44(1H, d), 6.83(2H, d), 7.11(2

H, d), 9.23(1H, s), 9.25(1H, s)

1-034

0.29-0.32(1H, m), 0.75-0.77(3H, m),

1.48-1.60(1H, m), 2.99(3H, s), 3.70(2H,

s), 4.84(1H, d), 7.17-7.33(5H, m), 9.25

(1H, s), 9.31(1H, s)

1-195

0.76-0.81(3H, t, 3H, t), 0.91-0.98(3

H, t, 3H, t), 1.36-1.41(3H, d, 3H, d),

2.64-2.90(1H, m, 1H, m), 2.75(3H, s), 2.85

(3H, s), 3.69-3.80(1H, q, 1H, q), 5.13(1

H, d), 5.51(1H, d), 7.17-7.31(5H, m, 5H,

m), 9.22(1H, s), 9.23(1H, s), 9.27(1H,

s), 9.30(1H, s), mixture of diastereoisomers

1-329

0.80(3H, d), 1.07(3H, d), 1.45(3H, s),

1.50(3H, s), 2.39(3H, s), 2.67-2.80(1

H, m), 5.58(1H, d), 7.08(2H, d), 7.25(2

H, d), 9.15(1H, s), 9.27(1H, s)

1-488

2.76(3H, s), 2.88(3H, s), 3.70(3H, s),

3.72(3H, s), 3.77(2H, s), 3.79(2H, s),

7.36-7.73(9H, m, 9H, m), 8.57(1H, s),

8.61(1H, s), 9.25(1H, s), 9.27(1H, s),

mixture of diastereoisomers

1-490

2.76(3H, s), 2.88(3H, s), 3.70(3H, s),

3.72(3H, s), 3.77(2H, s), 3.79(2H, s),

6.70-7.40(8H, m, 8H, m), 8.55(1H, s),

8.60(1H, s), 9.25(1H, s), 9.27(1H, s),

mixture of diastereoisomers

1-526

0.89(3H, d), 0.98(3H, d), 2.48-2.60(1

H, m), 2.68(3H, s), 2.92(3H, s), 3.63(2

H, s), 5.38(1H, d), 7.05-7.28(5H, m),

8.94(1H, s), 9.13(1H, s)

TABLE 41

Compound

No.

NMR (δ(ppm), 300MHz, TMS-CDCl

3

)

1-562

0.79(3H, d), 0.89(3H, d), 0.89(3H, d),

1.12(3H, t), 1.16(3H, d), 1.29(3H, t),

1.25(3H, d), 1.52(3H, d), 1.88(1H, t),

2.27(1H, t), 2.04-2.94(3H, m, 3H, m),

3.44-3.56(1H, m, 1H, m), 3.69-3.81(2H,

m), 3.90-4.00(2H, m), 5.77(2H, d, 2H,

d), 7.19-7.35(5H, m, 5H, m), 8.59(1H,

s), 8.61(1H, s), 9.00(1H, s), 9.08(1H,

s), mixture of diastereoisomers

1-592

0.90(3H, d), 1.01(3H, d), 1.36(3H, d),

2.53-2.65(1H, m), 2.73(3H, s), 3.78(1

H, q), 4.01(3H, s), 5.70(1H, d), 6.99(2

H, d), 7.18(2H, d), 8.89(1H, s), 9.16(1

H, s)

1-593

0.80(3H, d), 0.92(3H, d), 1.36(3H, d),

2.40-2.50(1H, m), 2.62(3H, s), 3.68(1

H, q), 4.02(3H, s), 5.76(1H, d), 7.14(2

H, d), 7.27(2H, d), 8.92(1H, s), 9.19(1

H, s)

1-595

0.80(3H, d), 0.91(3H, d), 1.35(3H, d),

1.45(3H, t), 2.40-2.50(1H, m), 2.63(3

H, s), 3.67(1H, q), 4.51(2H, q), 5.78(1

H, d), 7.14(2H, d), 7.27(2H, d), 8.92(1

H, s), 9.19(1H, s)

1-651

0.94(3H, t, 3H, t), 1.47(3H, d), 1.66(3

H, d), 1.88-1.98(2H, m, 2, m), 2.08(3H,

s), 2.09(3H, s), 2.61(3H, s), 2.68(3H,

s), 3.74(2H, dd, 2H, dd), 4.29(1H, q, 1H,

q), 6.03(1H, t), 6.12(1H, t), 7.23-7.37

(5H, m, 5H, m), 8.61(1H, s), 8.63(1H, s),

9.09(1H, s), 9.11(1H, s),

mixture of diastereoisomers

1-652

0.94(3H, t, 3H, t), 1.49(3H, d), 1.65(3

H, d), 1.91-1.99(2H, m, 2H, m), 2.07(3H,

s), 2.63(3H, s), 2.70(3H, s), 3.70(2H,

s, 2H, s), 4.25-4.32(1H, m, 1H, m), 6.01

(1H, t), 6.11(1H, t), 6.99-7.28(4H, m, 4

H, m), 8.62(1H, s), 8.64(1H, s), 9.10(1

H, s), 9.11(1H, s), mixture of diastereoisomers

TABLE 42

Compound

No.

NMR (δ(ppm), 300MHz, TMS-CDCl

3

)

1-872

0.77(3H, d), 0.97(3H, d), 1.37(3H, d),

2.85(3H, s), 2.81-2.91(1H, m), 3.77(1

H, q)5.14(1H, d), 7.16-7.29(5H, m)9.22

(1H, s), 9.29(1H, s)

1-873

0.80(3H, d), 1.15(3H, d), 2.43(3H, s),

2.76-2.84(1H, m), 3.18(3H, s), 5.23(1

H, d), 6.77(2H, d), 7.02(1H, t), 7.15(2

H, d), 9.16(1H, s), 9.26(1H, s)

1-877

0.82(3H, t), 0.93(3H, t), 1.72(3H, s),

1.78(3H, s), 1.86-1.92(2H, m), 2.77(3

H, s), 3.01(3H, s), 3.70(2H, s), 4.06(2

H, s), 3.70-4.20(4H, m), 5.86(1H, t),

6.09(1H, t), 7.14-7.30(4H, m), 8.70(1H,

s), 8.80(1H, s), 9.13(1H, s), 9.22(1H,

s)

1-878

0.89(3H, t), 0.97(3H, t), 1.70-1.90(2

H, m), 1.90-2.10(2H, m), 2.66(3H, s),

2.70(3H, s), 2.94(3H, s), 3.00(3H, s), 3.62

(2H, s), 3.73(2H, dd), 5.62(1H, t),

5.70-5.79(1H, m), 7.05-7.27(4H, m, 4H, m),

8.68(1H, s), 8.83(1H, s), 9.15(1H, s),

9.20(1H, s)

2-58

0.44-0.53(2H, m), 0.55-0.65(H, m),

1.16(3H, s), 3.13(3H, s), 3.80(2H, s), 5.64

(1H, s), 6.63(1H, d), 6.75(1H, d), 9.12

(1H, s), 9.26(1H, s)

2-75

0.89(3H, d), 0.99(3H, d), 1.23(3H, t),

2.43-2.51(1H, m), 2.71-3.05(2H, m),

2.77(3H, s), 3.80(2H, dd), 5.72(1H, d), 6.65

(1H, d), 6.74(1H, d), 8.61(1H, s), 9.06

(1H, s)

TABLE 43

Compound

No.

NMR (δ(ppm), 300MHz, TMS-CDCl

3

)

4-26

0.78(3H, t), 1.11-1.21(3H, m), 1.31(3

H, t), 2.36(3H, s), 2.58(3H, s), 2.44-2.67

(1H, m), 2.77(3H, s), 2.86(3H, s), 2.88-3.16

(2H, m), 5.02(1H, dd), 7.04-7.45

(4H, m), 8.52(1H, s), 8.69(1H, s), 9.01

(1H, s), 9.10(1H, s)

4-28

0.77(3H, d), 1.15(3H, d), 1.31(3H, t),

2.31(3H, s), 2.33-2.43(1H, m)2.80(3H,

s), 2.89-3.17(2H, m), 5.02(1H, d), 7.22-7.35

(4H, m), 8.52(1H, s), 9.01(1H, s)

4-36

0.77(3H, d), 1.12(3H, d), 2.48-2.58(1

H, m), 3.04(3H, s), 5.09(1H, d), 7.35-7.39

(2H, m), 7.46-7.54(3.H, m)9.05(1H,

s), 9.21(1H, s)

4-37

0.77(3H, d), 1.13(3H, d), 2.53-2.59(1

H,), 3.02(3H, s), 5.1(1H, d), 7.04-7.08

(2H, m), 7.54-7.58(2H, m)9.06(1H, s),

9.24(1H, s)

4-54

0.86(3H, t), 1.34(3H, t), 1.63-2.09(2

H, m), 2.76(3H, s), 2.91-3.09(2H, m), 5.27

(1H, dd)7.17-7.21(2H, m)7.72-7.79

(2H, m), 8.47(1H, s), 9.06(1H, s)

5-13

0.79(3H, d), 1.16(3H, d), 1.83-1.90(2H,

m), 2.91-2.99(1H, m), 3.07-3.14(3H, m),

3.32-3.40(1H, m), 4.40(1H, d), 4.68(1H,

d), 5.02(1H, d)7.20-7.33(5H, m), 9.25

(1H, s), 9.46(1H, s)

The herbicide of the present invention comprises the pyrimidine derivative represented by the formula [I] as an active ingredient.

In order to use the compound of the present invention as a herbicide, the compound of the present invention may be used by itself, but it may be used as formulated in e.g. a dust, a wettable powder, an emulsifiable concentrate, a microgranule or a granule by incorporating a carrier, a surfactant, a dispersant or an adjuvant which are commonly used for formulations. The carrier to be used for formulation may, for example, be a solid carrier such as talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, calcium carbonate, slaked lime, silica sand, ammonium sulfate or urea, or a liquid carrier such as isopropyl alcohol, xylene, cyclohexane or methylnaphthalene.

The surfactant and the dispersant may, for example, be a metal salt of an alkylbenzene sulfonic acid, a metal salt of dinaphthylmethanedisulfonic acid, an alcohol/sulfuric acid ester, an alkylaryl sulfonate, lignin sulfonate, polyoxyethylene glycol ether, polyoxyethylene alkylaryl ether, and polyoxyethylene sorbitan monoalkylate. The adjuvant may, for example, be carboxymethylcellulose, polyethylene glycol or gum Arabic. In the actual use, it may be applied as diluted to a proper concentration or may be directly applied.

The herbicide of the present invention can be used by application to foliage, application to soil or application to water surface. The blend proportion of the active ingredient may suitably be selected, as the case requires. However, in the case of a dust or a granule, it is preferably selected within a range of from 0.01 to 10% (weight), preferably from 0.05 to 5% (weight). Further, in the case of an emulsifiable concentrate and a wettable powder, it is preferably selected within a range of from 1 to 50% (weight), preferably from 5 to 30% (weight).

The dose of the herbicide of the present invention varies depending upon the type of the compound to be used, the objective weeds, the germination tendency, the environmental conditions as well as the formulation to be used. However, when it is used as it is, in the case of a dust or a granule, the dose is preferably selected within a range of from 0.1 g to 5 kg, preferably from 1 g to 1 kg, per 10 ares as an active ingredient. Further, in a case where it is used in a liquid state as in the case of an emulsifiable concentrate or wettable powder, the dose is preferably selected within a range of from 0.1 to 50,000 ppm, preferably from 10 to 10,000 ppm.

Further, the compound of the present invention may be used in combination with an insecticide, a fungicide, another herbicide, a plant growth regulator, a fertilizer, etc., as the case requires.

Now, the formulation method will be described in detail with reference to typical Formulation Examples. However, the compounds, the types of the additives and the blend ratios are not limited thereto and may be varied within wide ranges. In the following description, “parts” means “parts by weight”.

FORMULATION EXAMPLE 1: WETTABLE POWDER

To 10 parts of compound (1-8), 0.5 part of polyoxyethyleneoctylphenyl ether, 0.5 part of a sodium salt of β-naphthalene sulfonic acid formalin condensate, 20 parts of diatomaceous earth and 69 parts of clay were mixed and pulverized to obtain a wettable powder.

FORMULATION EXAMPLE 2: WETTABLE POWDER

To 10 parts of compound (1-8), 0.5 part of polyoxyethyleneoctylphenyl ether, 0.5 part of a sodium salt of β-naphthalene sulfonic acid formalin condensate, 20 parts of diatomaceous earth, 5 parts of white carbon and 64 parts of clay were mixed and pulverized to obtain a wettable powder.

FORMULATION EXAMPLE 3: WETTABLE POWDER

To 10 parts of compound (1-8), 0.5 part of polyoxyethyleneoctylphenyl ether, 0.5 part of a sodium salt of β-naphthalene sulfonic acid formalin condensate, 20 parts of diatomaceous earth, 5 parts of white carbon and 64 parts of calcium carbonate, were mixed and pulverized to obtain a wettable powder.

FORMULATION EXAMPLE 4: EMULSIFIABLE CONCENTRATE

To 30 parts of compound (1-8), 60 parts of a mixture of equal amounts of xylene and isophorone, and 10 parts of a mixture comprising a surfactant polyoxyethylenesorbitan alkylate, a polyoxyethylene alkylaryl polymer and an alkylaryl sulfonate, were added, followed by thorough stirring to obtain an emulsifiable concentrate.

FORMULATION EXAMPLE 5: GRANULE

10 parts of compound (1-8), 80 parts of an extender having talc and bentonite mixed in a ratio of 1:3, 5 parts of white carbon, 5 parts of a mixture comprising a surfactant polyoxyethylenesorbitan alkylate, a polyoxyethylene alkylaryl polymer and an alkylaryl sulfonate, and 10 parts of water were mixed and thoroughly kneaded to obtain a paste, which was extruded through a screen having openings having a diameter of 0.7 mm, then dried and cut into a length of from 0.5 to 1 mm to obtain a granule.

Now, the effects of the compound of the present invention will be described with reference to Test Examples.

TEST EXAMPLE 1: TESTS OF HERBICIDAL EFFECTS BY FLOODED PADDY FIELD TREATMENT

In a 100 cm

2

plastic pot, paddy field soil was filled and paddled. Then, seeds of barnyard grass (Eo) and monochoria (Mo) were sown, and water was introduced to a depth of 3 cm. Next day, a wettable powder prepared in accordance with Formulation Example 1 was diluted with water and dropwise applied to the water surface. The dose was 100 g of the active ingredient per 10 ares. Thereafter, cultivation was carried out in a green house, and on the 21st day after the treatment, the herbicidal effects were examined in accordance with the standards as identified in Table 44. The results are shown in Tables 45 to 52.

TABLE 44

Herbicidal effects (growth-

inhibition degree) and

Index number

phytotoxity

5

Herbicidal effect or

phytotoxity for controlling

more than 90%

4

Herbicidal effect or

phytotoxity of at least 70%

and less than 90%

3

Herbicidal effect or

phytotoxity of at least 50%

and less than 70%

2

Herbicidal effect or

phytotoxity of at least 30%

and less than 50%

1

Herbicidal effect or

phytotoxity of at least 10%

and less than 30%

0

Herbicidal effect or

phytotoxity of at least 0%

and less than 10%

TABLE 45

Compound No.

Dose (gai/10a)

Eo

Mo

1-4

100

5

5

1-8

100

5

5

1-9

100

5

5

1-10

100

5

5

1-12

100

5

5

1-13

100

5

5

1-15

100

5

5

1-16

100

5

5

1-17

100

5

5

1-18

100

5

5

1-19

100

5

5

1-20

100

5

5

1-21

100

5

5

1-22

100

5

5

1-23

100

5

5

1-24

100

5

5

1-25

100

5

5

1-26

100

5

5

1-27

100

5

5

1-32

100

5

5

1-33

100

5

5

1-34

100

5

5

1-35

100

5

5

1-36

100

5

5

1-37

100

5

5

1-38

100

5

5

1-39

100

5

5

1-40

100

5

5

1-41

100

5

5

1-42

100

5

5

1-43

100

5

5

1-44

100

5

5

1-45

100

5

5

1-46

100

5

5

1-47

100

5

5

1-48

100

5

5

1-49

100

5

5

1-50

100

5

5

1-51

100

5

5

1-52

100

5

5

1-53

100

5

5

1-54

100

5

5

1-55

100

5

5

1-56

100

5

5

1-57

100

5

5

1-58

100

5

5

1-59

100

5

5

1-60

100

5

5

1-61

100

5

5

1-62

100

5

5

1-63

100

5

5

1-64

100

5

5

1-65

100

5

5

TABLE 46

Compound No.

Dose (gai/10a)

Eo

Mo

1-66

100

5

5

1-67

100

5

5

1-68

100

5

5

1-70

100

5

5

1-71

100

5

5

1-72

100

5

5

1-74

100

5

5

1-75

100

5

5

1-76

100

5

5

1-78

100

5

5

1-80

100

5

5

1-81

100

5

5

1-82

100

5

5

1-83

100

5

5

1-84

100

5

5

1-85

100

5

5

1-86

100

5

5

1-87

100

5

5

1-88

100

5

5

1-89

100

5

5

1-90

100

5

5

1-91

100

5

5

1-93

100

5

5

1-94

100

5

5

1-95

100

5

5

1-96

100

5

5

1-97

100

5

5

1-98

100

5

5

1-99

100

5

5

1-100

100

5

5

1-101

100

5

5

1-102

100

5

5

1-103

100

5

5

1-104

100

5

5

1-105

100

5

5

1-106

100

5

5

1-107

100

5

5

1-111

100

5

4

1-112

100

5

5

1-113

100

5

5

1-114

100

5

5

1-115

100

5

5

1-116

100

5

5

1-118

100

5

5

1-119

100

5

5

1-120

100

5

5

1-121

100

5

5

1-122

100

5

5

1-123

100

5

5

1-124

100

5

5

1-125

100

5

5

1-126

100

5

5

1-127

100

5

5

TABLE 47

Compound No.

Dose (gai/10a)

Eo

Mo

1-128

100

5

4

1-129

100

5

5

1-130

100

5

5

1-131

100

5

5

1-132

100

5

5

1-133

100

5

5

1-134

100

5

5

1-135

100

5

5

1-136

100

5

5

1-137

100

5

5

1-138

100

5

5

1-139

100

5

5

1-140

100

5

5

1-141

100

5

5

1-142

100

5

5

1-143

100

5

5

1-144

100

5

5

1-145

100

5

5

1-146

100

5

5

1-147

100

5

5

1-148

100

5

5

1-150

100

5

5

1-151

100

5

5

1-152

100

5

5

1-153

100

5

5

1-154

100

5

5

1-155

100

5

5

1-156

100

5

5

1-159

100

5

5

1-160

100

5

5

1-161

100

5

5

1-162

100

5

5

1-163

100

5

5

1-164

100

5

5

1-165

100

5

5

1-166

100

5

5

1-167

100

5

5

1-168

100

5

5

1-169

100

5

5

1-170

100

5

5

1-171

100

5

5

1-172

100

5

5

1-173

100

5

5

1-174

100

5

5

1-175

100

5

5

1-177

100

5

5

1-178

100

5

4

1-180

100

5

5

1-181

100

5

5

1-182

100

5

5

1-183

100

5

5

1-184

100

5

5

1-185

100

5

5

TABLE 48

Compound No.

Dose (gai/10a)

Eo

Mo

1-186

100

5

5

1-187

100

5

5

1-188

100

5

5

1-189

100

5

5

1-190

100

5

5

1-191

100

5

5

1-192

100

5

5

1-193

100

5

5

1-194

100

5

5

1-195

100

5

5

1-196

100

5

5

1-197

100

5

5

1-198

100

5

5

1-200

100

5

5

1-214

100

5

5

1-217

100

5

5

1-218

100

5

5

1-219

100

5

5

1-220

100

5

5

1-221

100

5

5

1-222

100

5

5

1-225

100

5

5

1-226

100

5

5

1-228

100

5

5

1-234

100

5

5

1-249

100

5

5

1-250

100

5

5

1-251

100

5

5

1-254

100

5

5

1-265

100

5

5

1-266

100

5

5

1-267

100

5

5

1-270

100

5

5

1-273

100

5

5

1-274

100

5

5

1-305

100

5

5

1-306

100

5

5

1-307

100

5

5

1-310

100

5

5

1-321

100

5

5

1-322

100

5

5

1-323

100

5

5

1-324

100

5

5

1-325

100

5

5

1-327

100

5

5

1-328

100

5

5

1-329

100

5

5

1-330

100

5

5

1-331

100

5

5

1-333

100

5

5

1-334

100

5

5

1-335

100

5

5

1-401

100

5

5

TABLE 49

Compound No.

Dose (gai/10a)

Eo

Mo

1-402

100

5

5

1-403

100

5

5

1-404

100

5

5

1-407

100

5

5

1-409

100

5

5

1-410

100

5

5

1-411

100

5

5

1-412

100

5

5

1-413

100

5

5

1-414

100

5

5

1-415

100

5

5

1-416

100

5

5

1-417

100

5

5

1-418

100

5

5

1-419

100

5

5

1-420

100

5

5

1-421

100

5

5

1-422

100

5

5

1-424

100

5

5

1-425

100

5

5

1-426

100

5

5

1-427

100

5

5

1-428

100

5

5

1-429

100

5

5

1-430

100

5

5

1-431

100

5

5

1-432

100

5

5

1-433

100

5

5

1-434

100

5

5

1-435

100

5

5

1-436

100

5

5

1-437

100

5

5

1-438

100

5

5

1-439

100

5

5

1-441

100

5

5

1-442

100

5

5

1-443

100

5

5

1-444

100

5

5

1-445

100

5

5

1-446

100

5

5

1-447

100

5

5

1-448

100

5

5

1-449

100

5

5

1-450

100

5

5

1-451

100

5

5

1-452

100

5

5

1-454

100

5

5

1-455

100

5

5

1-458

100

5

5

1-459

100

5

5

1-460

100

5

5

1-461

100

5

5

1-463

100

5

5

TABLE 50

Compound No.

Dose (gai/10a)

Eo

Mo

1-464

100

5

5

1-465

100

5

5

1-469

100

5

5

1-473

100

5

5

1-476

100

5

5

1-482

100

5

5

1-483

100

5

5

1-484

100

5

5

1-485

100

5

5

1-486

100

5

5

1-487

100

5

5

1-488

100

5

5

1-489

100

5

5

1-490

100

5

5

1-491

100

5

5

1-492

100

5

5

1-493

100

5

5

1-494

100

5

5

1-495

100

5

5

1-496

100

5

5

1-497

100

5

5

1-498

100

5

5

1-499

100

5

5

1-500

100

5

5

1-501

100

5

5

1-502

100

5

5

1-504

100

5

5

1-505

100

5

5

1-506

100

5

5

1-507

100

5

5

1-510

100

5

5

1-511

100

5

5

1-517

100

5

5

1-518

100

5

5

1-519

100

5

5

1-520

100

5

5

1-521

100

5

5

1-524

100

5

5

1-526

100

5

5

1-527

100

5

5

1-528

100

5

5

1-529

100

5

5

1-530

100

5

5

1-532

100

5

5

1-533

100

5

5

1-535

100

5

5

1-536

100

5

5

1-537

100

5

5

1-538

100

5

5

1-539

100

5

5

1-540

100

5

5

1-541

100

5

5

1-546

100

5

5

TABLE 51

Compound No.

Dose (gai/10a)

Eo

Mo

1-547

100

5

5

1-548

100

5

5

1-549

100

5

5

1-550

100

5

5

1-551

100

5

5

1-553

100

5

5

1-555

100

5

5

1-558

100

5

5

1-559

100

5

5

1-560

100

5

5

1-561

100

5

5

1-562

100

5

5

1-563

100

5

5

1-565

100

5

5

1-566

100

5

5

1-567

100

5

5

1-569

100

5

5

1-571

100

5

4

1-572

100

5

5

1-573

100

5

5

1-579

100

5

5

1-584

100

5

5

1-586

100

5

5

1-589

100

5

5

1-591

100

5

5

1-592

100

5

5

1-593

100

5

5

1-594

100

5

5

1-595

100

5

5

1-597

100

5

5

1-598

100

5

5

1-599

100

5

5

1-600

100

5

5

1-602

100

5

5

1-603

100

5

5

1-604

100

5

5

1-606

100

5

5

1-607

100

5

5

1-608

100

5

5

1-609

100

5

5

1-611

100

5

5

1-614

100

5

5

1-615

100

5

5

1-624

100

5

5

1-626

100

5

5

1-627

100

5

5

1-637

100

5

5

1-639

100

5

5

1-640

100

5

5

1-641

100

5

5

2-1

100

5

5

2-2

100

5

5

2-3

100

5

5

TABLE 52

Compound No.

Dose (gai/10a)

Eo

Mo

2-5

100

5

5

2-6

100

5

5

2-7

100

5

5

2-8

100

5

5

2-9

100

5

5

2-10

100

5

5

2-11

100

5

5

2-12

100

5

5

2-13

100

5

5

2-14

100

5

5

2-19

100

5

5

2-20

100

5

5

2-23

100

5

5

2-24

100

5

5

2-25

100

5

5

2-31

100

5

5

2-32

100

5

5

2-41

100

5

5

2-42

100

5

5

2-44

100

5

5

2-46

100

5

5

2-48

100

5

5

2-50

100

5

5

2-51

100

5

5

2-52

100

5

5

2-53

100

5

5

2-54

100

5

5

2-55

100

5

5

2-56

100

5

5

2-57

100

5

5

2-58

100

5

5

2-59

100

5

5

2-60

100

5

5

2-61

100

5

5

2-62

100

5

5

2-63

100

5

5

2-71

100

5

5

2-72

100

5

5

2-73

100

5

5

2-74

100

5

5

2-75

100

5

5

2-77

100

5

5

2-78

100

5

5

2-80

100

5

4

4-1

100

5

5

4-2

100

5

5

TEST EXAMPLE 2: TEST OF HERBICIDAL EFFECTS BY UPLAND SOIL TREATMENT

In a 80 cm

2

plastic pot, upland soil was filled, and seeds of barnyard grass (Ec) and green foxtail (Se) were sown and covered with soil. A wettable powder prepared in accordance with Formulation Example 1 was diluted with water and uniformly applied to the soil surface by means of a small size spray at a rate of 100 l per 10 ares, so that the dose of the active ingredient would be 100 g per 10 ares. Thereafter, cultivation was carried out in a green house, and on the 21st day after the treatment, the herbicidal effects were examined in accordance with the standards as identified in Table 44. The results are shown in Tables 53 to 60.

TABLE 53

Compound No.

Dose (gai/10a)

Ec

Se

1-8

100

5

5

1-9

100

5

5

1-10

100

4

4

1-12

100

5

5

1-13

100

5

5

1-15

100

5

5

1-16

100

4

5

1-17

100

4

4

1-20

100

5

5

1-21

100

5

5

1-22

100

5

5

1-23

100

5

5

1-24

100

5

5

1-25

100

5

5

1-26

100

5

5

1-27

100

5

5

1-32

100

5

5

1-33

100

5

5

1-34

100

5

5

1-35

100

5

5

1-36

100

5

5

1-37

100

5

5

1-38

100

5

4

1-40

100

5

4

1-41

100

5

5

1-42

100

5

5

1-45

100

5

5

1-46

100

5

5

1-47

100

5

5

1-48

100

5

5

1-49

100

5

4

1-50

100

5

5

1-51

100

5

5

1-52

100

5

5

1-53

100

5

5

1-54

100

5

5

1-55

100

5

5

1-56

100

5

5

1-57

100

5

5

1-58

100

5

5

1-59

100

5

5

1-60

100

5

5

1-61

100

5

5

1-62

100

4

4

1-63

100

5

5

1-64

100

5

5

1-65

100

5

5

1-66

100

5

5

1-67

100

5

5

1-68

100

5

5

1-70

100

5

5

1-71

100

5

5

1-72

100

5

4

TABLE 54

Compound No.

Dose (gai/10a)

Ec

Se

1-74

100

5

5

1-75

100

5

5

1-76

100

5

5

1-77

100

5

5

1-78

100

5

5

1-80

100

5

5

1-81

100

5

5

1-83

100

5

5

1-85

100

5

5

1-87

100

5

5

1-88

100

5

5

1-89

100

5

5

1-90

100

5

5

1-91

100

4

5

1-92

100

5

5

1-95

100

5

5

1-96

100

5

5

1-97

100

5

5

1-98

100

5

5

1-99

100

5

5

1-100

100

5

5

1-101

100

5

5

1-102

100

5

5

1-103

100

5

5

1-105

100

5

5

1-106

100

5

4

1-11

100

5

5

1-112

100

5

5

1-113

100

5

4

1-114

100

5

5

1-115

100

5

5

1-116

100

5

4

1-118

100

5

5

1-119

100

5

4

1-120

100

5

4

1-121

100

5

4

1-122

100

5

5

1-123

100

5

5

1-124

100

5

5

1-125

100

5

5

1-126

100

5

5

1-127

100

5

5

1-128

100

5

5

1-130

100

5

5

1-131

100

5

5

1-133

100

5

5

1-134

100

5

5

1-135

100

5

5

1-136

100

5

5

1-137

100

5

5

1-138

100

5

5

1-139

100

5

5

1-140

100

5

5

TABLE 55

Compound No.

Dose (gai/10a)

Ec

Se

1-141

100

5

5

1-142

100

5

5

1-143

100

5

5

1-144

100

5

5

1-145

100

5

5

1-146

100

4

4

1-147

100

5

5

1-148

100

5

5

1-150

100

5

5

1-151

100

5

5

1-152

100

5

5

1-153

100

5

5

1-155

100

4

4

1-159

100

5

5

1-160

100

5

5

1-161

100

5

5

1-162

100

5

4

1-163

100

5

5

1-164

100

5

5

1-165

100

5

5

1-166

100

5

5

1-167

100

5

5

1-168

100

5

5

1-169

100

5

5

1-170

100

5

5

1-171

100

5

4

1-172

100

5

5

1-173

100

5

5

1-174

100

5

5

1-177

100

4

4

1-180

100

5

5

1-181

100

5

5

1-182

100

5

5

1-186

100

5

5

1-187

100

5

5

1-190

100

4

4

1-192

100

5

5

1-193

100

5

5

1-194

100

5

5

1-195

100

5

5

1-196

100

5

5

1-197

100

5

5

1-198

100

5

5

1-200

100

5

5

1-214

100

5

5

1-217

100

5

5

1-218

100

5

5

1-219

100

5

5

1-220

100

5

5

1-222

100

5

5

1-225

100

5

5

1-226

100

5

4

1-228

100

5

5

TABLE 56

Compound No.

Dose (gai/10a)

Ec

Se

1-234

100

5

5

1-249

100

5

5

1-250

100

4

5

1-251

100

5

5

1-254

100

5

5

1-265

100

5

5

1-266

100

5

5

1-267

100

5

5

1-270

100

5

5

1-273

100

5

5

1-274

100

5

5

1-305

100

5

5

1-306

100

5

5

1-307

100

5

5

1-310

100

5

5

1-321

100

5

5

1-323

100

4

4

1-326

100

4

4

1-327

100

5

5

1-328

100

5

5

1-329

100

5

5

1-330

100

5

5

1-331

100

5

5

1-332

100

5

5

1-333

100

5

5

1-334

100

5

5

1-335

100

5

5

1-401

100

5

5

1-402

100

5

5

1-403

100

5

5

1-404

100

5

5

1-407

100

5

5

1-409

100

5

5

1-410

100

5

5

1-411

100

5

5

1-412

100

5

5

1-414

100

4

5

1-416

100

5

5

1-417

100

5

5

1-418

100

5

5

1-419

100

5

5

1-424

100

5

5

1-425

100

5

5

1-426

100

5

5

1-427

100

5

5

1-428

100

5

5

1-429

100

5

5

1-430

100

5

5

1-431

100

5

5

1-432

100

5

5

1-433

100

5

5

1-434

100

5

5

1-435

100

5

5

TABLE 57

Compound No.

Dose (gai/10a)

Ec

Se

1-436

100

5

5

1-437

100

5

5

1-438

100

5

5

1-439

100

5

4

1-441

100

5

5

1-442

100

5

5

1-443

100

5

5

1-444

100

5

5

1-445

100

5

5

1-446

100

5

5

1-447

100

5

5

1-448

100

5

4

1-449

100

5

5

1-450

100

5

5

1-451

100

5

5

1-452

100

5

5

1-454

100

4

5

1-455

100

5

5

1-458

100

5

4

1-459

100

5

5

1-460

100

5

5

1-461

100

5

5

1-463

100

4

5

1-464

100

5

5

1-465

100

5

5

1-466

100

4

4

1-471

100

5

4

1-473

100

5

4

1-476

100

5

5

1-482

100

5

5

1-483

100

5

4

1-484

100

5

5

1-485

100

5

5

1-488

100

5

5

1-489

100

5

5

1-490

100

5

5

1-492

100

5

5

1-493

100

5

5

1-494

100

5

5

1-495

100

5

5

1-496

100

5

4

1-497

100

5

5

1-498

100

5

5

1-499

100

5

4

1-502

100

4

4

1-504

100

5

5

1-505

100

5

5

1-506

100

5

5

1-507

100

5

5

1-508

100

5

5

1-511

100

4

4

1-517

100

5

5

1-518

100

5

5

TABLE 58

Compound No.

Dose (gai/10a)

Ec

Se

1-519

100

5

5

1-520

100

5

5

1-521

100

5

5

1-523

100

4

5

1-524

100

5

5

1-526

100

5

5

1-527

100

5

5

1-528

100

5

5

1-529

100

5

5

1-530

100

5

5

1-531

100

4

4

1-532

100

5

5

1-533

100

5

5

1-535

100

5

5

1-536

100

5

5

1-537

100

5

5

1-538

100

5

5

1-539

100

5

5

1-540

100

5

5

1-541

100

5

4

1-546

100

5

5

1-547

100

5

5

1-548

100

5

5

1-549

100

5

5

1-550

100

5

5

1-551

100

5

5

1-553

100

5

5

1-555

100

5

5

1-558

100

5

5

1-559

100

5

5

1-560

100

5

5

1-561

100

5

4

1-562

100

5

5

1-563

100

5

5

1-565

100

5

5

1-566

100

5

5

1-567

100

5

5

1-569

100

5

5

1-571

100

5

5

1-572

100

5

5

1-573

100

5

4

1-579

100

5

5

1-584

100

5

5

1-586

100

5

5

1-589

100

5

5

1-591

100

5

5

1-592

100

5

5

1-594

100

5

5

1-597

100

4

4

1-598

100

5

4

1-600

100

4

5

1-602

100

5

5

1-603

100

4

4

TABLE 59

Compound No.

Dose (gai/10a)

Ec

Se

1-604

100

5

4

1-606

100

5

5

1-607

100

4

4

1-608

100

5

5

1-609

100

5

4

1-611

100

5

5

1-614

100

5

5

1-616

100

5

5

1-617

100

5

5

1-618

100

5

5

1-619

100

5

5

1-620

100

5

5

1-621

100

5

5

1-622

100

4

5

1-623

100

5

4

1-624

100

5

5

1-625

100

4

5

1-626

100

5

4

1-627

100

5

5

1-636

100

4

4

1-639

100

5

5

1-640

100

4

4

1-641

100

5

4

1-642

100

4

4

1-646

100

4

4

2-1

100

5

4

2-2

100

5

4

2-6

100

5

4

2-7

100

5

5

2-8

100

5

5

2-9

100

5

5

2-10

100

5

5

2-11

100

5

5

2-12

100

5

5

2-13

100

5

5

2-14

100

5

5

2-19

100

5

5

2-20

100

5

5

2-23

100

5

5

2-24

100

5

5

2-25

100

5

5

2-31

100

5

5

2-32

100

5

5

2-44

100

5

5

2-46

100

5

5

2-47

100

4

5

2-50

100

5

5

2-51

100

5

5

2-52

100

5

5

2-53

100

5

5

2-54

100

5

5

2-55

100

5

5

2-56

100

5

5

TABLE 60

Compound No.

Dose (gai/10a)

Ec

Se

2-57

100

5

5

2-58

100

5

5

2-59

100

5

4

2-60

100

5

5

2-61

100

5

5

2-62

100

5

5

2-63

100

5

4

2-71

100

5

5

2-72

100

5

5

2-73

100

5

5

2-74

100

5

5

2-75

100

5

5

2-77

100

5

5

2-78

100

5

5

2-79

100

5

5

4-1

100

5

5

4-2

100

5

4

TEST EXAMPLE 3: TEST OF HERBICIDAL EFFECTS BY FOLIAGE TREATMENT IN UPLAND FIELD

In a 80 cm

2

plastic pot, upland soil was filled, and seeds of barnyard grass (Ec) and green foxtail (Se) were sown and cultured in a green house for 2 weeks. Then, a wettable powder prepared in accordance with Formulation Example 1 was diluted with water and applied to the entire foliage from above the plants by means of a small size spray at a rate of 100 l per 10 ares so that the dose of the active ingredient would be 100 g per 10 ares. Thereafter, cultivation was carried out in a green house, and on the 14th day after the treatment, the herbicidal effects were examined in accordance with the standards of Table 44. The results are shown in Tables 61 to 64.

TABLE 61

Compound No.

Dose (gai/10A)

Ec

Se

1-1

100

4

4

1-8

100

5

4

1-9

100

5

4

1-10

100

4

4

1-12

100

5

4

1-13

100

5

4

1-21

100

4

4

1-22

100

4

4

1-24

100

4

4

1-26

100

4

4

1-27

100

4

4

1-41

100

5

4

1-42

100

4

4

1-46

100

4

4

1-47

100

4

4

1-48

100

5

4

1-50

100

4

4

1-53

100

4

4

1-54

100

5

4

1-55

100

4

4

1-56

100

4

4

1-57

100

5

4

1-58

100

4

4

1-59

100

4

4

1-60

100

4

4

1-61

100

4

4

1-66

100

5

4

1-78

100

5

4

1-81

100

4

4

1-83

100

5

4

1-87

100

4

4

1-88

100

4

4

1-89

100

5

4

1-92

100

5

4

1-95

100

5

5

1-96

100

5

5

1-98

100

4

4

1-100

100

5

5

1-107

100

4

4

1-111

100

4

4

1-112

100

4

5

1-113

100

4

4

1-122

100

4

4

1-127

100

4

4

1-129

100

5

5

1-133

100

5

4

1-137

100

5

4

1-142

100

4

4

1-143

100

4

4

1-144

100

4

4

1-152

100

4

4

1-153

100

4

4

1-164

100

4

4

TABLE 62

Compound No.

Dose (gai/10d)

Ec

Se

1-172

100

5

5

1-186

100

5

4

1-192

100

4

4

1-193

100

5

4

1-194

100

5

4

1-195

100

5

4

1-196

100

5

4

1-198

100

4

4

1-214

100

4

4

1-218

100

4

4

1-220

100

5

5

1-221

100

4

4

1-251

100

4

4

1-267

100

4

4

1-270

100

4

4

1-330

100

4

4

1-331

100

4

4

1-333

100

4

4

1-334

100

4

4

1-401

100

5

5

1-402

100

5

4

1-403

100

4

4

1-404

100

5

4

1-407

100

4

4

1-409

100

4

4

1-410

100

4

4

1-411

100

4

4

1-412

100

4

4

1-416

100

5

4

1-417

100

4

5

1-419

100

4

5

1-424

100

4

4

1-426

100

4

4

1-427

100

4

4

1-428

100

4

4

1-430

100

4

4

1-431

100

4

4

1-432

100

5

4

1-434

100

4

4

1-435

100

4

4

1-436

100

4

4

1-437

100

4

4

1-441

100

4

4

1-442

100

4

4

1-445

100

5

5

1-446

100

5

4

1-447

100

5

4

1-449

100

4

4

1-450

100

4

4

1-451

100

4

4

1-452

100

4

4

1-454

100

4

4

1-455

100

4

4

TABLE 63

Compound No.

Dose (gai/10a)

Ec

Se

1-459

100

4

4

1-461

100

4

4

1-463

100

4

4

1-464

100

4

4

1-473

100

5

4

1-482

100

5

4

1-484

100

5

5

1-486

100

4

4

1-488

100

5

4

1-489

100

4

4

1-490

100

4

4

1-492

100

5

4

1-493

100

4

4

1-494

100

5

4

1-496

100

4

4

1-497

100

4

4

1-504

100

5

4

1-505

100

5

5

1-506

100

4

4

1-507

100

4

4

1-508

100

4

4

1-517

100

4

4

1-519

100

4

4

1-526

100

5

4

1-527

100

4

4

1-528

100

4

4

1-529

100

5

4

1-530

100

4

4

1-532

100

5

4

1-536

100

4

4

1-537

100

4

4

1-538

100

4

4

1-539

100

4

4

1-540

100

4

4

1-541

100

4

4

1-546

100

4

4

1-547

100

4

4

1-558

100

4

4

1-559

100

4

4

1-560

100

4

4

1-661

100

5

4

1-563

100

5

4

1-565

100

5

4

1-566

100

4

4

1-569

100

5

4

1-571

100

4

4

1-572

100

4

4

1-579

100

4

4

1-584

100

4

4

1-586

100

5

4

1-589

100

4

4

1-591

100

4

4

1-592

100

5

4

TABLE 64

Compound No.

Dose (gai/10a)

Ec

Se

1-594

100

5

5

1-598

100

4

4

1-600

100

5

4

1-602

100

4

4

1-606

100

4

4

1-607

100

4

4

1-609

100

4

4

1-611

100

4

4

1-617

100

4

4

1-619

100

4

4

1-622

100

4

4

1-642

100

4

4

2-11

100

5

4

2-12

100

5

4

2-23

100

4

4

2-25

100

5

4

2-46

100

4

4

2-50

100

4

4

2-51

100

4

4

2-53

100

4

4

2-57

100

5

5

2-60

100

4

4

2-61

100

4

4

2-62

100

4

4

2-71

100

5

4

2-74

100

4

4

2-75

100

5

4

2-79

100

4

4

4-2

100

5

4

TEST EXAMPLE 4: TEST OF SELECTIVITY FOR A CROP PLANT BY FLOODED PADDY FIELD TREATMENT

In a 100 cm

2

plastic pot, a paddy field soil was filled and paddled. Then, seeds of barnyard grass (Eo) and monochoria (Mo) were sown, and rice (Or) of second leaf stage was transplanted, and water was introduced to a depth of 3 cm. Next day, a wettable powder prepared in accordance with Formulation Example 1 was diluted with water and dropwise applied to the water surface. The dose was 25 g of the active ingredient per 10 ares. Thereafter, cultivation was carried out in a green house, and on the 21st day after the treatment, the herbicidal effects were examined in accordance with the standards of Table 44. The results are shown in Tables 65 to 69.

TABLE 65

Compound No.

Dose (gai/10s)

Eo

Mo

Or

1-4

25

5

4

1

1-13

25

5

5

1

1-16

25

5

5

1

1-17

25

5

5

1

1-18

25

5

4

1

1-20

25

5

5

1

1-21

25

5

5

1

1-22

25

5

5

1

1-23

25

5

5

1

1-26

25

5

5

1

1-33

25

5

5

1

1-34

25

5

5

1

1-36

25

5

5

1

1-38

25

5

5

0

1-39

25

5

5

0

1-40

25

5

5

0

1-41

25

5

5

0

1-42

25

5

5

0

1-43

25

5

5

1

1-44

25

5

5

0

1-45

25

5

5

0

1-46

25

5

5

0

1-47

25

5

5

0

1-48

25

5

5

1

1-49

25

5

5

0

1-50

25

5

5

1

1-51

25

5

5

1

1-52

25

5

5

1

1-53

25

5

5

1

1-54

25

5

5

1

1-55

25

5

5

1

1-59

25

5

5

0

1-60

25

5

5

1

1-61

25

5

5

1

1-62

25

5

5

1

1-63

25

5

5

1

1-67

25

5

5

1

1-72

25

5

5

0

1-74

25

5

5

0

1-76

25

5

5

0

1-78

25

5

5

1

1-81

25

5

5

0

1-82

25

5

5

0

1-83

25

5

5

1

1-84

25

5

5

0

1-85

25

5

5

0

1-86

25

5

5

0

1-87

25

5

5

1

1-89

25

5

5

0

1-91

25

5

5

1

1-93

25

5

5

0

1-97

25

5

5

0

1-98

25

5

5

1

TABLE 66

Compound No.

Dose (gai/10a)

Eo

Mo

Or

1-99

25

5

5

1

1-103

25

5

5

1

1-104

25

5

5

1

1-106

25

5

5

0

1-107

25

5

5

0

1-113

25

5

5

0

1-116

25

5

5

0

1-118

25

5

3

0

1-119

25

5

5

0

1-120

25

5

5

0

1-121

25

5

5

1

1-123

25

5

5

1

1-124

25

5

5

0

1-125

25

5

5

0

1-126

25

5

5

1

1-130

25

5

5

1

1-131

25

5

5

1

1-132

25

5

5

0

1-133

25

5

5

1

1-134

25

5

5

0

1-135

25

5

5

1

1-136

25

5

5

1

1-137

25

5

5

1

1-139

25

5

5

0

1-140

25

5

5

0

1-141

25

5

5

1

1-144

25

5

5

1

1-145

25

5

5

1

1-146

25

5

5

1

1-147

25

5

5

1

1-150

25

5

5

1

1-152

25

5

5

1

1-153

25

5

5

1

1-161

25

5

5

0

1-162

25

5

5

0

1-166

25

5

5

1

1-167

25

5

5

1

1-168

25

5

5

1

1-169

25

5

5

1

1-170

25

5

5

1

1-171

25

5

5

1

1-172

25

5

5

1

1-175

25

5

5

0

1-180

25

5

5

1

1-181

25

5

5

1

1-182

25

5

5

1

1-183

25

5

5

0

1-188

25

5

5

0

1-189

25

5

5

0

1-190

25

5

5

0

1-197

25

5

5

0

1-200

25

5

5

1

1-217

25

5

5

1

TABLE 67

Compound No.

Dose (gai/10a)

Eo

Mo

Or

1-218

25

5

5

1

1-219

25

5

5

1

1-220

25

5

5

1

1-221

25

5

5

1

1-225

25

5

5

0

1-226

25

5

5

1

1-228

25

5

5

0

1-234

25

5

5

1

1-250

25

5

5

1

1-251

25

5

5

1

1-306

25

5

5

1

1-321

25

5

5

1

1-324

25

5

5

1

1-325

25

5

5

1

1-329

25

5

5

1

1-333

25

5

5

1

1-334

25

5

5

0

1-401

25

5

5

1

1-404

25

5

5

1

1-412

25

5

5

1

1-416

25

5

5

1

1-417

25

5

5

1

1-418

25

5

5

1

1-425

25

5

5

1

1-436

25

5

5

1

1-439

25

5

5

1

1-441

25

5

5

1

1-442

25

5

5

1

1-443

25

5

5

1

1-444

25

5

5

1

1-448

25

5

5

1

1-452

25

5

5

0

1-454

25

5

5

1

1-455

25

5

5

1

1-459

25

5

5

1

1-461

25

5

5

1

1-465

25

5

5

0

1-473

25

5

5

1

1-483

25

5

5

1

1-484

25

5

5

1

1-485

25

5

5

1

1-486

25

5

5

1

1-487

25

5

5

1

1-489

25

5

5

1

1-490

25

5

5

0

1-491

25

5

5

0

1-492

25

5

5

0

1-493

25

5

5

1

1-494

25

5

5

1

1-495

25

5

5

0

1-496

25

5

5

1

1-498

25

5

5

0

1-504

25

5

5

1

TABLE 68

Compound No.

Dose (gai/10a)

Eo

Mo

Or

1-505

25

5

5

0

1-506

25

5

5

1

1-507

25

5

5

1

1-511

25

5

5

0

1-517

25

5

5

1

1-519

26

5

5

1

1-520

25

5

5

1

1-521

25

5

5

1

1-527

25

5

5

1

1-528

25

5

5

1

1-529

25

5

5

1

1-530

25

5

5

1

1-532

25

5

5

1

1-533

25

5

5

1

1-541

25

5

5

1

1-547

25

5

5

1

1-548

25

5

5

1

1-549

25

5

5

0

1-551

25

5

5

0

1-553

25

5

5

1

1-558

25

5

5

1

1-566

25

5

5

1

1-567

25

5

5

1

1-569

25

5

5

1

1-572

25

5

5

1

1-573

25

5

5

1

1-579

25

5

5

1

1-584

25

5

5

1

1-559

25

5

5

1

1-591

25

5

5

1

1-593

25

5

4

0

1-594

25

5

5

1

1-598

25

5

5

1

1-599

25

5

5

1

1-604

25

5

5

1

1-606

25

5

5

1

1-607

25

5

5

1

1-608

25

5

5

1

1-609

25

5

5

1

1-611

25

5

5

1

1-614

25

5

5

1

1-615

25

5

5

1

1-624

25

5

5

1

1-626

25

5

5

1

1-627

25

5

5

1

1-639

25

5

4

1

2-1

25

5

5

0

2-2

25

5

5

1

2-7

25

5

5

1

2-8

25

5

5

0

2-19

25

5

5

1

2-20

25

5

5

1

2-25

25

5

5

1

TABLE 69

Compound No.

Dose (gai/10a)

Eo

Mo

Or

2-31

25

5

5

0

2-32

25

5

5

1

2-42

25

5

5

0

2-48

25

5

5

1

2-50

25

5

5

1

2-55

25

5

5

1

2-56

25

5

5

1

2-57

25

5

5

1

2-58

25

5

5

1

2-71

25

5

5

1

2-73

25

5

5

1

2-74

25

5

5

1

2-75

25

5

5

1

2-78

25

5

5

1

4-1

25

5

5

1

4-2

25

5

5

1

TEST EXAMPLE 5: TEST OF SELECTIVITY FOR A CROP PLANT BY SOIL TREATMENT IN UPLAND FIELD

In a 80 cm

2

plastic pot, upland soil was filled, and seeds of barnyard grass (Ec), green foxtail (Se), soybean (G1), wheat (Tr) and corn (Ze) were sown and covered with soil. A wettable powder prepared in accordance with Formulation Example 1 was diluted with water and uniformly applied to the soil surface by a small size spray at a rate of 100 l per 10 ares so that the dose of the active ingredient would be 25 g per 10 ares. Thereafter, cultivation was carried out in a green house, and on the 21st day after the treatment, the herbicidal effects were examined in accordance with the standards of Table 44. The results are shown in Table 70.

TABLE 70

Compound No.

Dose (gai/10a)

Ec

Se

Gl

Tr

Ze

1-15

25

5

5

—

1

1

1-23

25

5

5

—

2

1

1-33

25

4

4

0

2

1

1-42

25

5

5

0

0

0

1-45

25

4

5

0

2

0

1-46

25

5

5

1

3

0

1-48

25

4

5

0

1

0

1-49

25

5

5

1

0

3

1-50

25

4

5

3

3

0

1-51

25

5

5

0

1

0

1-53

25

4

5

1

2

0

1-54

25

4

5

0

1

0

1-55

25

5

4

1

1

0

1-56

25

5

5

0

4

3

1-58

25

5

5

0

3

0

1-59

25

5

5

0

1

0

1-60

25

5

5

1

2

0

1-61

25

5

5

1

3

0

1-64

25

4

4

2

3

0

1-65

25

5

5

0

0

0

1-68

25

4

4

0

2

2

1-70

25

5

4

1

4

1

1-71

25

5

5

—

3

0

1-75

25

4

4

0

3

2

1-76

25

4

4

0

2

2

1-77

25

5

5

1

3

2

1-78

25

5

5

0

1

0

1-80

25

5

5

0

5

1

1-81

25

4

4

0

1

0

1-83

25

5

5

1

2

1

1-84

25

4

4

0

1

0

1-85

25

4

4

0

1

0

1-89

25

4

5

0

2

2

1-95

25

5

5

1

0

0

1-97

25

4

4

3

1

0

1-98

25

4

5

0

1

1

1-99

25

4

4

0

3

0

1-100

25

5

5

0

2

2

Industrial Applicability

The compound of the present invention represented by the formula [I] exhibits excellent herbicidal effects over a wide range from preemergence to the growing period of various weeds which are problematic in upland fields, including, for example, broad leaf weeds such as smartweed, slender amaranth, lambsquaters, chickweed, velvetleaf, prickly sida, hemp sesbania, morning glory and cocklebur, perenial and annual cyperaceous weeds such as purple nutsedge, yellow nutsedge, himekugu, chufa and rice flatsedge, and glass weeds such as barnyard grass, crab grass, green foxtail, annual bluegrass, Johnson grass, water foxtail and wild oat. Further, it can control annual weeds such as barnyard grass, umbrella plant and monochoria, and perenial weeds such as Japanese ribbon wapato, arrowhead, water nutgrass, water chestnut, Japanese bulrush and narrowleaf waterplantain, which germinate in paddy fields. On the other hand, the herbicide of the present invetion has high safety to crop plants and exhibits particularly high safety to rice, wheat, barley, corn, grain solgum, soybean, cotton, beet, etc.

Number	Date	Country
764641	Mar 1997	EP
9622980	Aug 1996	WO

Pyrimidine derivatives and herbicides containing them

Information

Patent Number

Date Filed

Date Issued

Inventors

Original Assignees

Examiners

Agents

CPC

US Classifications

Field of Search

US

International Classifications

Term Extension

Abstract

Description

Claims

Priority Claims (1)

PCT Information

Foreign Referenced Citations (2)

Non-Patent Literature Citations (6)