SI8710087A8 - Process for preparation of substituted pyridinesulphonamide compound - Google Patents

Description

l υ j o u i r / o: '/ O *

ISHIHARA SANGYO KAISHA LTD. , - .. j) Ef / AJ / ~ / V >) AJ θβ / S

Japan:

PROCEDURE FOR THE PRODUCTION OF SUBSTITUTED PYRIDINSULPHONAMIDE

UNITS

Technical field

The invention relates to the field of herbicide production, and in particular relates to a process for the production of a new substituted pyridinsulfonamide compound.

According to the International Patent Classification, the invention is classified in classes C 07 D 401/12 and A 01 N 47/36.

Technical problem

The invention solves the problem of producing new herbicidally active pyridinsulfonamide compounds by introducing new specific substituents.

The state of the art

The substituted pyridinesulfonamide compound of the present invention is characterized in that the pyridine ring has an N-substituted amino-carbonyl group. Such a substituted pyridinsulfonamide compound is known by the general formulas in U.S.P.No.4,518,776, European Patent Application No.101670, and U.S.P. No.4,521,597. However, the substituted pyridinsulfonamide of the present invention is not specifically described in the foregoing patents. Some substituted pyridine sulfonamide compounds are described in U.S.P. No.4,435,206. However, with this compound, the pyridine ring is not N-substituted with the aminocarbonyl group. A number of herbicidal analogues have been developed that contain the sulfonamide compound as the active ingredient. However, no herbicides have been found so far that show high safety over cereals and which have high herbicidal effects.

Description of a solution to a technical problem with examples of execution

Here, the inventors have conducted extensive research into the relationship between chemical structure and physiological — anti-potent activity against sulfonamide compounds. By ^ bnp ^ .pvi .the last lasagna carried out further research for the sake of Jijop ^ l ^ zhej · cereal herbicide. As a result, these inventors

TEL: 5?: - ·; · * < >, 346-185 J [, TELEX 125i0 Mi KIJ ”TELEFAX 34from 2 that the pyridinsulfonamide compound 'having a pyridine ring with an N-substituted aminocarbonyl group, and in particular a substituted the group (if any) and the sulfonamide nucleus substituted on the nitrogen atom with the specifically substituted pyrimidin-2-ylaminocarbonyl group represents an effective herbicide in the cereal field, and so the inventors have come to the present invention.

The present invention provides a substituted pyridinesulfonamide compound, salts thereof, a herbicidal composition containing them, and a process for preparing them. Substituted pyridine sulfonamide compounds are represented by the following general formula:

XI ... (I) R-SO2NHC0NH ^ O ^ X2 0 0 II / R1 II / R1 in which R represents a ^ RZ group or Ji (Y) n ^ tK (Y) n 4 * 0 group, each of which R1 and R2 independently represent a hydrogen atom, an alkyl group, a haloalkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkoxy group, a haloalkoxyalkyl group, a cycloalkyl group, a halocycloalkyl group, an alkoxycarbonyl group, a haloalkoxycarbonyl group, a phenyl group or a phenyl group. , provided that when one of R1 and R2 represents a hydrogen atom, the other represents one of the groups except the hydrogen atom; R 1 and R 2 together with the adjacent nitrogen atom may form a heterocycle; Y represents a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkylthio group, a haloalkylthio group, alkoxyalkyl

a group, a haloalkoxyalkyl group, or -N. A R4 group (wherein each of R3 and R4 independently represents a hydrogen atom 3 or an alkyl group); n is O, or an integer 1 or 2; and each of X1 and X2 independently represents a methyl group, a methoxy group, or an ethoxy group.

Salts of the substituted pyridinesulfonamide compounds of the present invention include alkali metal salts (for example, sodium and potassium), alkaline earth metal salts (for example magnesium and calcium), and amine salts (for example monomethylamine, dimethylamine and triethylamine). These salts can be prepared by conventional methods.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT In general formula (I), haloalkyl, haloalkoxy, haloalkoxy-alkyl, haloalkoxy-carbonyl, halocycloalkyl or halo-phenyl groups represented by R1 and R2, and haloalkyl, haloalkoxy, haloalkylthio or haloalkoxyalkyl groups represented by Y may be substituted by Y or more halogen atoms.

The alkyl group or nucleus represented by R1, R2, R3, R4 and Y in the general formula (I) is a group or a nucleus having 1 to 6 carbon atoms, and examples of such groups are methyl, ethyl, propyl, and butyl . The alkenyl group or nucleus represented by R 1 and R 2 has 2 to 6 carbon atoms, and examples of such groups are the propenyl group and the butenyl group. An alkynyl group or a nucleus has 2 to 6 carbon atoms, and examples of such groups are the propynyl group and the butynyl group. The cycloalkyl group has 3 to 6 carbon atoms, and examples of such group are the cyclopropyl group, cyclobutyl group, cyclopentyl group, and cyclohexyl group. Examples of halogen atoms in R 1, R 2 and Y are the fluorine atom, the chlorine atom, the bromine atom and the iodine atom. R1 and R2 together with the nitrogen atom may form a heterocycle. Examples of heterocycles are the morpholine ring, the ethylenimine ring, the pyrrolidine ring, and the piperidine ring.

Among the substituted pyridinsulfonamide compounds represented by general formula (I), the compounds represented by 4 of the following general formula, and their salts, are preferred:

More preferred embodiments will be described below: (1) R1 represents a hydrogen atom or an alkyl group, and preferably a hydrogen atom or a methyl group, and R2 represents an alkyl group and preferably a methyl group. (2) Y represents a halogen atom, an alkyl group, a halo-alkyl group, an alkoxy group, or an alkoxy-alkyl group, and preferably a chlorine atom, a bromine atom, a methyl group, or a difluoromethyl group, each of which is bonded in 6 - position of the pyridine nucleus; n is 0, 1, or 2, and preferably 0 or Ϊ. (3) Each of X1 and X2 independently represents a methoxy group. (4) More specifically, the following compounds are preferred: N - [(4,6-dimethoxypyrimidin-2-yl) aminocarbonyl / -3-methyl-aminocarbonyl or dimethylaminocarbonyl-2-pyridinsulfonamine or 6-chloro- (or bromo-, difluoromethyl- or methyl -) - N / (4,6-dimethoxypyrimidin-2-yl) aminocarbonyl / -3-dimethylaminocarbonyl-2 pyridinsulfonamide. 5

Substituted pyridinsulfonamide compounds represented by the general formula (I) and their salts according to the present invention can be obtained by the following methods:

A pyridine compound represented by the general formula (II) R - SO2Z1 ... (II) wherein R represents as defined above and Z1 represents an NH2 group, -NCO group, -NHC0C1 group, or -NHCOOR4 group (where R5 represents alkyl or aryl group) is reacted with a pyrimidine compound represented by the following general formula:

... (III) wherein each of X3 and X4 independently represents a halogen atom, a methyl group, a methoxy group, or an ethoxy group, Z2 represents an NH2 group, -NCO group, -NHC0C1 group, or -NHCOOR4 group (where R5 represents as defined above), provided that when Z1 represents the NH2 group, Z2 represents the -NCO, -NHC0C1 or -NHCOORjj group, and that when Z2 represents the NH2 group, Z1 represents the -NCO, -NHC0C1 or -NHCOOR1 group. Then, if X 3 and / or X 4 represents a halogen atom, methoxylation or ethoxylation takes place. In addition, if desired, treatment is performed to produce salt. 6

More specifically, the pyridine sulfonamide compound and its derivative can be prepared by methods (A / to / G). Ια] r-so2nh2 (II-1) / N- + R5OCONH- (O (III-l) 'N-

XI -20 ~ + 100 ° C 0.l ~ 24h X2 [Β] (II-l)

0 ~ 100 ° C 0.l ~ 24h > (I) [C] (II-l)

-10 ~ 60 ° C 0.5 ~ 24h (III-3) X2 »(I) /

XI

[D] r-so2nhcoor5 (II-2) -20 ~ + 100 “C 0. l ~ 24h 7 [Ε] R-S02NC0 + (III -4) Q ~ I-'2 ~ 4 ¥ ~~ - * ( I) (II-3) [F] R-SO2NHC0C £ + (111-4) ...... ^ - > (I) (I1-4)

Hal [G] R-SO2NHC0NH- / c (11-5) XN-X3 CH3OH (orC2H50H) O ° C ~ temperature reflux ^ a ^ * ^ 0.5 ~ 24h ''

The following method can also be used: 130 ~ 250 ° C (I) 0.5 ~ 24h [H] R-SO2NHC0NH2 + (111-4) (I1-6) 8 In the reaction units of the method / A / to / H /, Hal denotes the halogen atom and R, R5, X, X2 and X3 are the same as described above. The compound represented by the general formula (11-5) can be prepared according to the sequence of methods / A / to / F /. The compound represented by general formula (II-6) can be readily prepared by reacting the compound represented by general formulas (11-2) through (II-4) with ammonia. The aryl group represented by R5 in the general formulas (III-1) and (II-2) may be a phenyl or naphthyl group which may be substituted with one or more chlorine atoms or one or more methyl groups. In methods (A) and (D), 1,8-diazabi-cyclo / 5.4,0 / -7-undecene can be added to accelerate reactions if desired. In the methods (B), (C), (E) and (F), 1,4-diazabicyclo (2.2.2) -octane may be added if desired. In the methods [B /, / C /, / E / and / F /, a base such as triethyl amine or pyridine may be added. Methods / A / to / H / are performed in the presence of solvent, if desired. Examples of solvents are: aromatic hydrocarbons (for example benzene, toluene, xylene and chlorobenzene); cyclic or acyclic aliphatic hydrocarbons (for example chloroform, carbon tetrachloride, methylene chloride, dichloroethane, trichloroethane, hexane and cyclohexane); ethers (eg diethyl ether, dioxane and tetrahydro-furan); nitriles (for example acetonitrile, propionitrile, or acrylonitrile); and aprotic polar solvents (for example dimethylsulfoxide and sulfolane). 9 (1) It has been shown that the pyridine compound (11-1f) in the general formula (11-1) as a starting material for the reaction formula can be obtained by the process of methods 1 and 2: 10

11

Mode 2

(II-l *) 12

Note: EG is ethylene glycol, MeOH is methanol, EtOH is ethanol DMF is dimethylformamide, DMSO is dimethylsulfoxide, BZ is a non-ethyl group, Bu (t) is a tertiary butyl group, and AcOH is acetic acid. (2) It has been shown that, if Y in the general formula (II-1 *) is an alkyl group substituted by one or more fluorine atoms, the product can also be prepared by the procedure shown in Method 3 below. 01 13 i: Mode 3

Br2CH:: «Γί CCi 4 6li:! / V.COOCH3

SO2NH-Bu (t) / COOCH ^ MBS BPO, CCt 4 • 01 ^ vn, COOCH3 SO2NH -Bu (t) ToT BrCH2 j SO2NH-Bu (t) / AgM03 // acetone · H2O. 01. ^ X / COO.CH3 O N '

AgNOi EtOH H2O

HOH2C Q1 .n ^ COOCH30¾. a / oO-NH-] OHC01, f2hc

Bu (t) (C2H5) 2NSF3 CH2C £ 2 O, • N > \, cooch3 SO2NH-Bu (t) Rl ^.

R2 MeOH

N H SO2NH -Bu (t) = (C2H5) 2NSF3 CH2C £ 2 Q1 ^^ v ^ cooch3

FH2C

01

FH2C

NHSO2HH-Bu (t) R1 R2

MeOH

CON JRl \ R2 SO2NH -Bu (t) 01

CON \

Rl R2

F2HC S02NH -Bu (t)

CF3COOH

Qlvx ^ CON (f fat X f2hc so2nh2

Rl R2 Q1 fh2c

CF3COOH

CON /

Rl ^ R2 S02NH2 14 Note

Ύ ". " COOCH ^

Starting material - / ^ - N CH SO2NH-Bu (t) can be obtained by application

COOH ch3 OH according to the methods shown in Methods 1 and 2. Q1 is a hydrogen atom or a halogen atom, NBS is N-bromosuccinimide, and BPO is benzoyl peroxide. Other abbreviations and symbols have the same meanings as described above. (3) It has been shown that, if Y is in the general formula (II-1 *) of an alkoxy, haloalkoxy, alkylthio or haloalkyl-thio group, the product can also be obtained by the process of method 4 below. 15 Mode 4

Ql _COOH qi ^^ cooch3 Cl

DMSO, COOCH3

01, R60

M e OH HCi 1) SOC £ 2 2) p ^ > NH-HCZ, (C2H5) 3N, CF3COOH

BZSH \ R2 sho2nh2 SBZ D Cl2, AcOH (50%) 2) NH2-Bu (t) ch2ca2

Cl

NaORg RgOH COOCH3 \ (CH 3) 3A £ «« < & CH2C * 2

/ benzene ^ Rl, CON 'O'

'N sb2 1) Cl2' AcOH (50%) 2) NH 2 -Bu (t) CH 2 Cl 2

M S02NH -Bu (t)

Xo < - | S02-NH-Bu (t) (Continued on Page 16) 16 (Continued on Page 15)

Note: R6 is alkyl or haloalkyl. Other abbreviations and symbols have the same meanings as described above. (4) It has been shown that if Y in the general formula (II-11) is an alkoxymethyl or haloalkoxymethyl group, the product may also be obtained by the method shown below. 17 Method 5

Ql

C0dCH3

Note: Abbreviations and symbols have the same meanings as described above. (5) It has been shown that if Y in the general formula (II-1 '} Z' R3 represents an -N ^ group, the product can also be obtained by R4 by the procedure shown below. 18 Method 6

Cl. with Bz >

R3 \ / NH, h2o R4 1) ct2, 2) NH3,

Note: Abbreviations and symbols have the same meanings as described above. (6) It has been shown that, if Y is in the general formula (11-1 ') of a halogen atom, the product can also be obtained by the method shown below. 19 19 Method 7

Note: Abbreviations and symbols have the same meanings as described above. (7) It has been shown that the 3-pyridinsulfonamiano compound represented by the general formula (II-1 *) can also be obtained by the method shown below 8. 20 Method 8 (Ύ) n

N H 2 1) NaNO 2

2) SO2, CuCZ, AcOH 3) IZU-Va (t)

SO2NH-Bu (t

1) n-C4H9. 2) CO 2 to ether COOH (Y) n

SO ^ NH-Bu ^ t) ch2n2 / ether COOCH3

21

Note: Abbreviations and symbols " have the same meanings as described above. (8) It has been shown that the pyridine N-oxide represented by the general formula (II-1 *) can also be obtained by the method shown below 9.

Mode 9

/ Rl (Y) n

0 SO2NH2 (II-1 '22 (9) It is shown that the compounds represented by the general formulas (II-2) to (II-4) can be obtained from the compounds represented by the general formula (II-1) by the procedure shown below 10h

Mode 10 1) CH3CH2CH2CH2NCO, K2CO3, acetone 2) COa2, xylol R-SO2NH2 - ----- --1 > R-SO2NHC0CA —For 'T1ie- ^ Rs 0 2 »CQ (.11-1) ( II-4) (II-3)

(I1-2)

The reaction conditions for obtaining the starting compound, such as reaction temperature, reaction time, growth-impeller used as needed, alkaline substance, etc., may suitably be selected from those conventionally used in analogous reactions.

Examples of synthesis of intermediates of the compounds of this invention will be described below:

Synthesis of Intermediates, Example 1 - Synthesis of 2-aminosulfonyl-5-chloro-N, N-dimethylnicotinamide / I / 6.5 g of 2,5-dichloronicotinic acid was mixed with 24.7 ml of thionyl chloride and the reaction was refluxed for 2 hours. After completion of the reaction, the excess thionyl chloride was distilled off and removed, and 39 ml of methylene chloride was added to the mixture and then 2.77 g of dimethylamine hydrochloride salt was added. 8.60 g of triethylamine was added dropwise over one hour, and the resulting mixture was allowed to react at room temperature for about one hour.

After completion of the reaction, the reaction product was handed over to water for extraction with methylene chloride. The methyl chloride layer was dried with anhydrous sodium sulfate and the methylene chloride was distilled off under reduced pressure. The residue obtained was purified by chromatography on a silica gel column, yielding 5.5 g of 2,5-dichloro-N, N-dimethylnicotinamide, melting point 120-122 ° C. (II) A mixture of 3.0 g of 2,5-dichloro-N, N-dimethylnicotinamide obtained in process (I), 1.70 g of benzylmercaptan, and 5 ml of dimethylsulfoxide were added dropwise to a suspension of 1.89 g of anhydrous potassium carbonate in 28 ml of dimethylsulfoxide at 80 ° C for about one hour. The resulting mixture was reacted at 130 to 140 ° C for 30 minutes.

After the reaction was complete, the reaction product was added to water for extraction with methylene chloride. The methylene chloride layer was dried with anhydrous sodium sulfate, and the methylene chloride was distilled off. . under reduced pressure. The resulting residue was purified by chromatography on a silica gel column to give 2.18 g of oily 2-benzylthio-5-chloro-N, N-dimethyl-nicotinamide. (III) Gas chlorine was introduced into 20 ml of 50% acetic acid solution containing 2.36 g of 2-benzylthio-5-chloro-N, N-dimethylnicotinamide at 0 to 5 ° C. The reaction was interrupted when excess chlorine appeared. 24

After completion of the reaction, the reaction product was added to 150 g of ice and 200 ml of methylene chloride to separate the methylene chloride layer. The layer was washed with 300 ml ice and water to cool to 0 ° C. Then tert.butylamine was added dropwise and the mixture was stirred until the temperature of this layer reached room temperature. The reaction solution was adjusted to slightly alkaline and the reaction was complete.

After completion of the reaction, the reaction product was added to water for extraction with methylene chloride. The extracted methylene chloride was washed with anhydrous sodium sulfate and the methylene chloride was distilled off. The residue obtained was purified by chromatography on a silica gel column to give 1.21 g of 2-tert-butylaminosulfonyl-5-chloro-N, N-dimethylnicotinamide with a melting point of 143 to 145 ° C. (Iv) 1.0 g of 2-tert-butylaminosulfonyl-5-chloro-N, N-dimethylnicotinamide obtained in process (III) was added to 10 ml of trifluoroacetic acid and the reaction was refluxed for one hour.

After completion of the reaction, the trifluoroacetic acid was distilled off from the reaction product under reduced pressure: The residue was then purified by chromatography on a silica gel column to give 0.71 g of 2-aminosulfonyl-5-chloro-N, N-dimethylnicotinamide with a melting point of 155 to 157 ° C. 25

Synthesis of intermediates, Example 2 -

Synthesis of 2-aminosulfonyl-6-chloro-N, N-dimethylnicotinamide (I) / Mixture 7.0 g of 2,6-dichloro-N, N-dimethylnicotinamide (mp 62.5 to 65 ° C) obtained from 2,6-dichloroonicotinic acid following the same procedure as in the process of (I) synthesis of the intermediates of Example 1, 3/8 g of benzyl alcohol and 20 ml of dimethylsulfoxide was added to a suspension of 6/6 g of anhydrous potassium carbonate in 50 ml of dimethyl sulfoxide at 130 ° to 140 ° C during for about one hour, and the resulting mixture reacted at 150 ° C for about two hours.

After completion of the reaction, the reaction product was poured into water for extraction with methylene chloride. The methylene chloride layer was dried with anhydrous sodium sulfate and the methylene chloride was distilled off under reduced pressure. The resulting residue was purified by chromatography on a silica gel column to give 6.0 g of oily 6-benzoyloxy-2-chloro-N, N-dimethylnicotinamide. (II) 0.69 g of 6-benzoyl-2-benzylthio-N, N-dimethylnicotinamide (oily product) obtained using 6-benzoyloxy-2-chloro-N, N-dimethyl-nicotinamide following the same procedure as described in process / II / synthesis of the intermediate of Example 1, was mixed with 6 cc of concentrated hydrochloric acid, and the resulting mixture was reacted with stirring at room temperature for about 15 hours. 26

After completion of the reaction, the reaction solution was poured into water to extract the desired product with methylene chloride. The methylene chloride layer was dried with anhydrous sodium sulfate and the methylene chloride was distilled off under reduced pressure. The residue obtained was purified by chromatography on a silica gel column to give 0.41 g of 2-benzylthio-N, N-dimethyl-6-hydroxynicotinamide having a melting point at 52 to 60 ° C. (III) 1.0 g of 2-benzylthio-N, N-dimethyl-6-hydroxynicotinamide obtained in the previous process (II) and 0.3 ml of dimethylformamide were poured into 5 ml of thionyl chloride, and the resulting mixture was refluxed for about one hour .

After completion of the reaction, the reaction product was poured into water to extract the desired product with methylene chloride. The methylene chloride layer was washed with water and dried with anhydrous sodium sulfate. The methylene chloride was then distilled off under reduced pressure, and the resulting residue was purified by chromatography on a silica gel column, yielding 0.45 g of oily 2-benzylthio-6-chloro-N, N-dimethyl-nicotinamide. 27 l / IV / Using the above product and following the same procedure as in processes / III / and / IV / of Example 1, 2-aminosulfonyl-6-chloro-Ν, Ν-dimethylnicotinamide was obtained with a melting point of 171 to 173 ° C. .

Synthesis of Intermediate Example 3 -

Synthesis of 2-Aminosulfonyl-N, N-dimethyl-6-ethoxynicotinamide / I / 0.231 g of metallic sodium was added to 50 ml of anhydrous ethanol to prepare an ethanolic solution of sodium ethoxide. 2.0 g of 2,6-dichloro-N, N-dimethyl-nicotinamide obtained following the same procedure as in average (I) for the synthesis of the intermediates of Example 1 were added to the solution and the mixture was reacted under reflux for about one hour. The reaction solution was added to water for extraction with methylene chloride. The methylene chloride layer was dried with anhydrous sodium sulfate and the methylene chloride was distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column to give 1.95 g of 2-chloro-N, N-dimethyl-6-ethoxynicotinamide. 28 / II / Using the above product and following the same procedure as in the processes of (II), (III), and (IV) site of the intermediate of Example 1, 2-aminosulfonyl-N, N-dimethyl-6-ethoxynicotinamide was obtained with the point mp 150.5 to 151.5 ° C.

Synthesis of intermediates, Example 4 -

Synthesis of 2-Aminosulfonyl-N, N-dimethyl-6-fluoronicotinamide / N / 0.302 g of 2-tert-butylaminosulfonyl-6-chloro-N, N-dimethylnicotinamide was added to 10 ml of dimethyl sulfoxide solution containing 0.116 g spray dried potassium fluoride, and the resulting mixture was reacted with stirring at 150 ° C for about 3 hours.

After completion of the reaction, the reaction solution was added to 100 ml of water for extraction with methylene chloride. The extracted substance was washed several times with water and dried over anhydrous sodium sulfate. The methylene chloride was distilled off under reduced pressure and the residue was purified by chromatography on a silica gel column to give 0.204 g of 2-tert-butylaminosulfonyl-N, N-dimethyl-6-fluoronicotinamide. (II) Using the product and following the same procedures as process / IV / synthesis of the intermediates of Example 1, 2-aminosulfonyl-N, N-dimethyl-6-fluoronicotinamide was obtained with a melting point of 164 to 165 ° C. 29

Synthesis of Intermediates, Example 5-Synthesis of 2-aminosulfonyl-N-methylnicotinamide / I / 250 ml of dry methanol was saturated with hydrochloric acid gas, and 250 ml of methanol and 30 g of 2-mercaponicotinic acid were added. The resulting solution was reacted overnight at room temperature.

After completion of the reaction, the reaction solution was converted to slightly alkaline with ammonia gas and methanol was distilled off under reduced pressure. The crystalline substance was then washed with water and treated. The process crystals were dried under reduced pressure to give 24 g of methyl-2-mercapto-nicotinate having a melting point of 136-140 ° C. (II) 10 g of methyl 2-mercaptonicotinate obtained by process (I) was added to the suspension prepared by diluting 50 ml of acetic acid with 50 ml of water. Chlorine gas was introduced into the reaction system at or below 0 ° C and the reaction was quenched when excess chlorine appeared.

After completion of the reaction, the resulting solution was added to a mixture of 150 g of ice and 500 ml of methylene chloride to separate the methylene chloride layer. The layer was washed with 500 ml of ice and water and cooled to 0 ° C. Then, 12.9 g of tert-butylamine 1 was added dropwise to the above solution until it was brought to room temperature. 30

After stirring, the reaction solution was added to 500 ml of water and extracted with methylene chloride. After drying with sodium sulfate, methylene chloride was distilled off to give 13 g of crude crystals. The crystals were recrystallized from methylene chloride and normal hexane to give methyl 2-tert-butylaminosulfonylnicotinate having a melting point of 169 to 171 ° C. / III / 1.0 g of this product was added to 20 ml of anhydrous methanol, excess methylamine was absorbed and stirred for 15 hours.

After completion of the reaction, the reaction product was poured into water for extraction with methylene chloride. After extraction, the layer was dried with anhydrous sodium sulfate and the methylene chloride was distilled off under reduced pressure. 0.73 g of 2-tert-butylamino-sulfonyl-N-methylnicotinamide having a melting point of 189 to 192 ° C. is thus obtained. / IV / Using the product and following the same procedure as in the process / IV / synthesis of the intermediates of Example 1, 2-aminosulfonyl-N-methylnicotinamide was obtained having a melting point of 207 to 209.5 ° C. 31

Synthesis of intermediates, Example 6 -

Synthesis of 2-aminosulfonyl-N, N-dimethylnicotinamide / Method A / / I / Under nitrogen atmosphere, at 10 ° C or below, 10 ml of normal hexane containing 19% trimethylaluminum was added to the solution prepared by dissolving 1.3 ml of dimethylamine in 10 ml of anhydrous benzene. The resulting mixture reacted until its temperature reached room temperature. A solution was added to the reaction solution prepared by dissolving methyl-o-2-tert-butylaminosulfonylnicotinate in 40 ml of benzene and 20 ml of methylene chloride. The resulting mixture was then stirred under reflux for about 9 hours.

After completion of the reaction, the reaction solution was poured into dilute hydrochloric acid for extraction with methylene chloride. The extracted substance was dried with anhydrous sodium sulfate, methylene chloride was distilled off under reduced pressure, and the residue was purified chromatographically on a silica gel column to give 1.0 g of 2-tert-butylaminosulfonyl-N, N-dimethylnicotinamide. (II) Using the above product and following the same procedure as in process / IV / synthesis of the intermediates of Example 1, 2-aminosulfonyl-N, N-dimethyl-nicotinamide was obtained having a melting point of 209 to 211 ° C. 32 / Method B /

Chlorine gas was introduced into 50 ml of 50% acetic acid solution and 2.7 g of 2-benzylthio-N, N-dimethyl-nicotinamide until excess chlorine appeared.

After completion of the reaction, the reaction mixture was added to 200 ml of ice and water for extraction with 60 ml of methylene chloride. The methylene chloride layer was then washed with 100 ml of ice and water and cooled to 0 ° C. Gaseous ammonia was introduced into the solution until alkaline solution was reached. After the methylene chloride was distilled off, 15 ml of water were added to the residue, and the resulting mixture was stirred. The resulting crystals were filtered and washed with a small amount of water. The crystals were then dried under reduced pressure to give 1.27 g of 2-aminosulfonyl-N, N-dimethyl-nicotine amide having a melting point of from 209 to 211 ° C.

Synthesis of intermediates, Example 7 -

Synthesis of 2-aminosulfonyl-N-ethyl-N-methylnicotinamide / I / A mixture of 30 g of 2-chloronicotinic acid and thionyl chloride reacted under reflux for 4 hours. After the excess thionyl chloride was distilled from the reaction solution under reduced pressure, 500 ml of methylene chloride was added, and the gaseous methylamine was brought to room temperature until the solution became slightly alkaline. The methylamine chloride 4 33 obtained was graded, and the graded solution was condensed. The precipitated crystals were recrystallized from normal hexane and methylene chloride to give 27 g of 2-chloro-N-methylnicotinamide having a melting point of 106 to 107 ° C. (II) 10 ml of dimethylformamide containing 5 g of 2-chloro-N-methylnicotinamide prepared by the same procedure as in process (I) of this example was added dropwise at 0 to 5 ° C in the suspension obtained by adding 1.17 g of 60% sodium hydride in 50 ml of dimethylformamide. The resulting mixture was reacted at 0 to 5 ° C for about 30 minutes, and 3.5 g of ethyl bromide was added dropwise at 0 ° C. The resulting solution was reacted at room temperature for 2.5 hours, and the reaction solution was poured into water to extract with methylene chloride. The extracted substance was washed with water and dried with anhydrous sodium sulfate. The methylene chloride was then distilled off under reduced pressure and the residue was purified chromatographically on a silica gel column to give 5.7 g of oily 2-chloro-N-ethyl-N-methyl-nicotinamide. (III) Using this product and following the same procedure as processes (II) to (IV) of the synthesis of the inter-media of Example 1, 2-aminosulfonyl-N ethyl-N-methylnicotinamide was obtained having a melting point of 202 to 203 ° C. 34

Synthesis of intermediates, Example 8 -

Synthesis of 2-Aminosulfonyl-N, N-dimethyl-6-methylnicotinamide / I / One drop of dimethylformamide was added to a mixture of 1.35 g of 2-hydroxy-6-methylnicotinic acid and 15 ml of thionyl chloride, and the resulting solution was reacted under reflux conditions about 2 hours. The excess thionyl chloride was distilled off under reduced pressure, and 50 ml of methylene chloride was added to the residue. The resulting mixture was added to a mixture of 30 ml of 30% aqueous dimethylamine and 50 ml of methylene chloride, and the resulting solution was reacted at room temperature for 15 minutes.

After the reaction was complete, the reaction mixture was poured into water for extraction with methylene chloride. The methylene chloride layer was washed with water and dried with anhydrous sodium sulfate. Methylene chloride was distilled off under reduced pressure and the residue was purified by chromatography on a silica gel column to give 1.57 g of 2-chloro-3-N, N-dimethylamino-carbonyl-6-methylpyridine (m.p. 66-67.5 ° C). / II / Using this product and following the same procedure as in processes / II / to / IV / for the synthesis of intermediates of Example 1, 2-aminosulfonyl-N, N-dimethyl-6-methylnicotinamide was obtained having a melting point of 188.5 to 190.5 ° C. 35

Synthesis of intermediates, Example 9 - λ

Synthesis of 2-Aminosulfonyl - N, N-dimethyl-6-methoxynicotinamide / I / 33 g 2.6 dichloronicotinic acid and 100 ml of thionyl chloride were stirred and reacted under reflux for about 3 hours.

After the reaction was complete, excess thionyl chloride was distilled off under reduced pressure, and 500 ml of methylene chloride was added. Anhydrous methanol was added to the mixture at a temperature ranging from room temperature to 40 ° C. After instillation, the resulting mixture was reacted under reflux for about one hour.

After the reaction was complete, the reaction solution was added to 500 ml of water and partitioned with methylene chloride. As the residue was washed with water and dried with anhydrous sodium sulfate, the methylene chloride was distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column to give 27 g of methyl-2,6-dichloronicotinate having a melting point of 45.5 to 48.0 ° C. / II / Using this product and following the same O · procedure as in the process of synthesis of intermediates from Example-3, / II / synthesis of intermediates from Example 1 (Method A), / I / synthesis of intermediates from Example 6 and / III / to / IV / synthesis of the intermediate of Example 1, 2-amino-sulfonyl-N, N-dimethyl-6-methoxynicotinamide was obtained. 36

Synthesis of intermediates, Example 10 - '

Synthesis of 2-Aminosulfonyl-6-difluoromethyl-N, N-dimethyl-nicotinamide w / 1 / A mixture of 11.5 g of methyl-2-tert-butylaminosulfonyl-6-methylnicotinate obtained following the same procedure as in Processes (I) and (II) syntheses of the intermediates from Example 5, 186 ml of carbon tetrachloride, 14.84 g of N-bromosuccinimide, and 0.68 g of benzoyl peroxide were heated at reflux for three hours.

After the reaction was complete, the reaction mixture was treated, and the filter solution was condensed and purified by chromatography on a silica gel column to give 4.5 g of methyl-2-tert-butylaminosulfonyl-6-dibromomethyl-nicotinate. / II / 3.7 g of silver nitrate was added to a mixture of 4.4 g of the above product, 35 ml of ethanol and 29 ml of water, and the resulting mixture was heated and refluxed for 3 hours.

After the reaction was complete, the reaction mixture was added to water for extraction with methylene chloride. The extract substance was washed with water and dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by chromatography on a silica gel column to give 2.92 g of methyl-2-tert-butylaminosulfonyl-6-formylnicotinate, / III / 5 ml of methylene chloride solution and 0.62 g of diethylaminotrifluoride sulfur was added to 19 ml of methylene chloride solution of 0.48 g of methyl-2 -tert-butylaminosulfonyl-6-formyl-nicotinate, and the mixture was stirred for one hour at room temperature. 37

After the reaction was complete, the reaction mixture was added to water, extracted with methylene chloride, washed with water, and dried with anhydrous sodium sulfate. After that, the solvent was distilled off. The residue was purified by chromatography on a silica gel column to give 0.25 g of methyl-2-tert-butylaminosulfonyl-6-difluoromethylnicotinate. / IV / A mixture of 0.50 g of the above product and 10 ml of anhydrous methanol saturated with dimethylamine was left overnight at room temperature.

After completion of the reaction, the solvent was distilled off from the reaction mixture, and the residue was purified by chromatography on a silica gel column to give 0.15 g of 2-tert-butylaminosulfonyl-6-difluoromethyl-N, N-dimethyl-nicotinamide. (V) Using the above product and following the same procedure as in process / IV / synthesis of the intermediates of Example 1, 2-aminosulfonyl-6-difluoromethyl-N, N-dimethylnicotinamide was obtained.

Synthesis of intermediates, Example 11 -

The synthesis of 2-aminosulfonyl-6-bromo-N, N-dimethylnicotinamide / I / 5 ml acetic acid is. added to 1.2 g of 2-benzylthio "6-chloro-N, N-dimethyl-nicotinamide, and the resulting mixture was heated to 70 ° C. Hydrogen bromide hydrogen gas was introduced into this mixture for 30 minutes and the mixture reacted for another 30 minutes. 38

After completion of the reaction, the reaction mixture was cooled and added to ice water, extracted with methylene chloride, washed with sodium bicarbonate solution and then with water, and dried with anhydrous sodium sulfate.

The methylene chloride was distilled off and the residue was chromatographed on a silica gel column to give 1.0 g of 2-benzylthio-6-beomo-N, N-dimethylnicotinamide having a melting point of 105 to 106 ° C. (II) Using this product and following the same procedure as in Processes (III) and (IV) of the synthesis of intermediates of Example 1, 2-amino-sulfonyl-6-bromo-N, N-dimethylnicotinamide having a melting point of 154 to 156 ° C.

Typical examples of compounds represented by the general formula (II-1 ') are shown in Table 1. * &' & ki: Ι ·, ... - 39 -Table 1 * · O *

11; lyricists ·: i :: ..: ··!: ':!: ;;! and IS

Ir: U '^ Ι ^ ϋϊ: l i ·: I:! -! Π-: '(Y) n ·

^ " Rl 'V ^ R2 SO2NH2

Hi '· ./11-17 · ;; ·

Intermediate compound no. (Y) n 0 II -CU-f \ R2 Sulfonamide- position. not groups Melting point (° C) Location Rl R2 1: H 3 CH3 phenyl · 2 235-238 2 tl tt II ch2gf3 It - 3 H 11 II II - 4 '6-F • 1 II ch3 tl 164-165 5 H II «1 cooch3 II 168-170 6 II It II C3H7 (n) II - 7 4,6- {CH3) 2 II H ch3 II 220-221 8 6-ca ^ bi, 4m M • 1 ch3 II II 150.5 -151.5 9 H tl H II II 207-209.5 10 II • 1 II C2H5 II. 164-172 40 (Table '1, continuation p.39) λ 11 H 3 H C3H7 (i zo) 2 152-153 12 II «1 ch3 ch3 II 209-211 13 H II It c2h5 It 202-203 14 II II c2h5 It It - 15 cn 1 O h »II ch3 ch3 tl 155-157 16 6-C2H5 It tl It 11 153-154 17 H II H ci: 2ch = čh2 II 152-153.5 18 II II II 2 3 It 190-196 19 It II It phenyl II 186-189 20 4,6 (CH3) 2 II ch3 ch3 11 199-202 21 6-Br II H C2H5 II - 22 H II II ce2cr2oce3 tl 170.5-172.5 23 6-CH- OCH. .1 j II ch3 ch3 II - 24 5-C1-6, 0CH3 II II «1 tl 212-214 25 H II H cyclopropyl tl 180-182 26 tl II It CH ^ CsCE - II 203-205 27. •. . II It (CH2) 4 “II 206-209 41 (Table 1, continued with p.39) 28 6-CL 3 ch3 ch3 2 171-173 29 6-CH3 tl II II II 1. ; 188.5-190.5 30 6-OCH3 tl tl 11 II - 31 6-C2H5 II II It 11 153-154 32 6-CH3 11 H II II 230-231.5 33 H II -CH2CH2OCH2CH2-0 II 236-238 34 6-N { CH3) 2 II ch3 ch3 II - 35 6-SC5L, 11 It tl II 195.5-197 36 6-NHCH3 It II ti It 212-213 37 6-CH2F tl It 11 II - 38 6-CHF2 II 11 II II —- 39 H II It 2,4-difluoro-phenyl 11 232-237 40 (1 II H 'CH2! 3CH3- II -. 41 o-CH2OCK2CF3 II ch3 ch3 11 - 42 H 4 H It 3 239-241 43 M 2 CH3 II 'n II - 44 6-OCK..CF, L ·. O 3 II 11 2 42 (' table 1, continued with p.39) - 45 6-No 3 ch3 ch3 2 154-156 46 6-OCHoCHU L · 5 4 II II II - 47 H II II II 11 - 48 II 2 II II 3 169-170 49 6-03117 (iso) 3 II tl 2 - 50 5-CHF2 II «1 11 It - 51 6-CF3 II II It tl 151-153 52 It II 11 c2h5 II - 53 II - tl H ch3 II - 54 6-CH3 II ch3 c2h5 II - 55 6-Br II H ch3 II - 56 6-CA n tl II II; " - 57 6-CHF2 1 «M tl It - 43 - Examples of the synthesis of compounds of the invention will be described below. *

Synthesis Example No. 1 - Synthesis of 5-Chloro-N - [(4,6-dimethoxy-pyrimidin-2-yl) aminocarbonyl] -3-dimethylaminocarbonyl-2-pyrimidinesulfonamide (compound # 9) 0.19 g of 1,8-diazabicyclo /5.4.0/-7- undecene was added to the suspension prepared by adding 0.30 g of 2-aminosulfonyl-5-chloro-N, N-dimethylnicotinamide and 0.35 g of 2-phenoxy-carbonylamino-4,6-dimethoxypyrimidine in 10 ml of anhydrous acetonitrile, and the resulting mixture was reacted at room temperature for 45 minutes.

After completion of the reaction, the reaction mixture was added to water and the insoluble substance was treated. The filter solution was converted to a weakly acidic solution of concentrated hydrochloric acid and extracted with methylene chloride. The solution was then dried over anhydrous sodium sulfate, and the solution was distilled off to give 0.26 g of the desired compound with a melting point of 152 to 155 ° C.

Examples of synthesis no. 2 to 13

The same procedure as in Example Synthesis No. 1 was performed and the results obtained are shown in Table 2.

44 TO • n C - ^ ^ u TO -n o Ji H ° frn3 o E- < -P VD 00 (—and 2 ro co

ON o OJ 2 co o OJ and σ \ ΓΟ er * m 00. H 1 m co 1 N • H S o. · Cn

Φ *! “L C m CU rH * ΓΊ -S

CN i oz m r- OJ -n C OJ • ro • 5 'd 1¾ o

Q) TO

d -n -5 00 c σ \ r— (σν φ • mc »-HO and • ΓΟ • P • 0 • T3 0 • 2 O 1¾ 2 O and r» P < u id- 'ap cj E 3 o < In jJ - · H (d

TOI

u 0) to a p E 3 a > -p to TO

OJ

Table l I ΓΊ —I about XI. < 0 " C N. TO m o - · h J ai en • o O Ό I c CO X 3 «· -P I • h a r * OJ o o vo o Γ ιο

o oo O

toe £ r (0 0) (S

~ zrc iI

i 1 — I O · Η oj • P U £ d) JJ ^ ϋ -P < C 0! • n C OJ • n • 5'S • n 8 NS, • H • S en) Ό: - '

m m s · n: u _ o ° -sCr ° Ύ • E: 2. 0 = 0: O (Z) CJN o 00 vo »“ H θ 'H S i— | = OJ • • * o o o V $ • H p H a «I p oo P D 04 ® · Γ > c flj o H K. 2 O to

and θ 'OJ

about m

OJ m in

o Z

J _ X - 45 - - r J _. (Ο &

c < D

& P o o n · CN > —I ί m in cr »« cr H l p * «c < - > > r * > H i en io CN c r-; r — C l mo Γ

1 N ΉS Oj cn Q) n C -h Q) CN • n -H * H O 2 * 3 Π m d3 (N • n »-5 * * 3 ·

en CN

C • HS o 2 O m en ω • nS • m • S * • O o d) 2 • " 3 η m O r- N-

CN S, E £ 3 (D 4J H < 0 CJ o Γ I r- ^ o jD · m -vn. ≪ om • rHP_i Ό OI Ή “3 • —I ϋ cr S. &Quot; S a) lu < U n} ap £ 3 a jj ΐΰ in and o

O n CN is not and

O H CN • O • H I • H Λ k -H e < P E P • H c and m

c -H'S

o CN N " o vo ΓΟ

• 5 p -rH A 1 3-i P Qj N · φ Tl CT3 M Si and cs o O 2

O o n I «. CN S-J S · - < φ-π JJ-rj. = ¾ o m e 2

* M J-l Q) φ · ΓΛ jj-rj c'S m O 2 o o m P N iE f-5 0 · 03 O 2 io co * en 46 Melting point U o 170-174 206-207.5 •. 201.5-203.5 194-195 Q) ω. ω d) " Λ * r— > • m • Γ " »• m O 3 -a · 3 and 3 m 3 CK? d) mod) m CX \ d) -a * O d) -a · ON cn • ncmp r- • n I- Ό ·, CN o - .5 · .5 »-H -5 · .b · rH u -rt o • 'to • v ° • -3 o • PU Φ Z o ω 2 o Φ 2 o Φ 2 o Ό Ό • 3 S 2 £ rH H f * H rH 8 tu 1 u -r-4 -H d) m - (d d > (to £ Oi U CJ sau 5 - • iti 1¾ E 3 e • SE 3 o cn K 3 d) HX) (QS ® UJ X) flj! r 1 “Ί • H o JO • Π3 * r C oooo N ♦ < u as r- KD O: (0 in O - H o rH. IO .. 'i: • HJ —1 fl) CT • • • • 1 · T5 O Ό - oooo ·· '· 1 * —1 C ,. * j * i co -¾ 3 «. 1 i-H u p »• H C (0 § o in o o M« H oi * -H fH rH Tl 0 -H £ • H 4- > H w £ d) i c υ -h rij < C 3 mn UL * MM wc 808 • H 2 O z Π5 (U 3 • H ^ V o 00 oos 0) 3 cr «Mri« T m as H π ^ m 2 mst — fz CN with rH c • H o - = u • • • • P • ok O ooooc * • n S 0 c 3 N -H 1 ^ θ '1 3 O lu in lu ® (0 Tl - 5-1 d) (N o 5-id) mm 5j d) · *! · o 5-id) mo «H 'r! cr Φ 'P o φ-rp CN m -m o ψ -O o s M • H a * c «0 n • x) Ie. O • x) " H · o m • OJ * H · c1 »0 rH • W B z o M g Z o M g Z o M g. Z o d) S-i N 9! O rH CM Γ0 s 4-J M r4 rH rH u o * 1 0 · m c; · - 1. 3 U5 • H + j > N • γΊ O 5-1 a § ιΗ o x c (D • r. C -H s «c £ d) m P * with respect to the same in 47

Synthesis Example No 14 - Synthesis of N - [(4,6-dimethoxypyrimidin-2-yl) aminocarbonyl] -3-dimethylaminocarbonyl-2-pyridine sulfonamide

Method 1

A mixture of a solution of 250 mg of 2-amino-4,6-dimethoxy-pyrimidine, 0.65 g of triethylamine, and 2.5 g of ethyl acetate was added dropwise to 6.9 g of ethyl acetate solution containing 20% phosgene at 15 ° C, and the mixture was maintained at 15 ° C and reacted for one hour. The mixture was then heated to 90 ° C in an oil bath, and the excess phosgene and ethyl acetate were distilled off. A solution was then prepared by dissolving 300 mg of 2T-aminosulfonyl-N / N-dimethyl-nicotinamide in 10 ml of acetonitrile, which was added dropwise to the above mixture and 0.2 g of triethylamine was then added dropwise. The resulting mixture was reacted at room temperature for one hour.

After completion of the reaction, the product was added to water and acidified with hydrochloric acid and the precipitated ***. crystals superimposed. The crystals were washed with water and dried to give 0.46 g of the desired product.

Method 2 / I / 2.12 g of 2-aminosulfonyl-N, N-dimethylnicotinamide was added to 5 ml of dimethylformamide suspension containing 60% sodium hydride at -5 ° C, and the resulting mixture was reacted for about one hour. 10 ml of dimethylformamide solution 2.14 g of diphenylcarborrst was added to the above solution at -5 ° C. The solution was heated at room temperature for about 30 minutes to complete the reaction. The reaction solution was added to water and washed with methylene chloride. The aqueous layer was converted to acidic solution with hydrochloric acid and then extracted with methylene chloride. The methylene chloride layer was dried with anhydrous sodium sulfate, and the methylene chloride was distilled off under reduced pressure. The crystals obtained were recrystallized from ethyl acetate and hexane to give 0.91 g of N, N-dimethyl-2-phenoxycarbonylaminosulfonyl-nicotinamide with a melting point of 189 to 194 ° C. (II) 0.28 g of N, N-dimethyl-2-phenoxycarbonyl-amino-sulfonylnicotinamide prepared by method (N) and 0.14 g of 2-amino-4-chloro-6-methoxypyrimidine were added to 8 ml of anhydrous dioxane, and the resulting mixture reacted under reflux conditions for about 40 minutes.

After the reaction was complete, the reaction mixture was added to 200 ml of water, and the resulting crystals were purified to give 0.21 g of N - [(4-chloro-6-methoxy-pyrimidin-2-yl) aminocarbonyl] -3- dimethylaminocarbonyl-2-pyridinsulfonamide having a melting point of from 157 to 158.5 ° C. (III) 18.3 mg of metallic sodium was added to 7 ml of anhydrous methanol, and then 0.11 g of 49 N- ((4-chloro-6-methoxypyrimidin-2-yl) aminocarbonyl / -3-dimethylaminocarbonyl-2-pyridinsulfonamide prepared above was added. procedure / II /. The resulting mixture was heated and refluxed for 12 hours.

After the reaction was complete, the reaction mixture was added to water and converted into acidic solution with hydrochloric acid, and the precipitated crystals were washed, washed with water and dried to give 70 mg of the desired product.

Typical compounds represented by general formula (I) and their salts according to the present invention will be shown in Table 3.

XI 50

Table 3

The compound t! O. (Y) n 0 II / R1 -Cn '\ R2 Position of the sulfone amide group XI X2 Melting point (° C) Position of R1 R2 1 H 3 H. α- ^ ςκ = € Κ2 · 2 -Of »U ΟΟί3 · 165.5-167.5 2 fl It II ΓΎΤ ^ 1 -2 ^ 3 II M II 109-116 3 X II It Ο ^ Ο ^ ΟΟ ^ II II II 144.5- 146 4 II tl II cyclopropyl II II 1 «181-182 5 II II -CH2CH20CH2CH2- II II II 159-161 6 II II ch3 och3 II II II 179-182 7 II II II phenyl II tl II 114-119

Dos.2036 CYR-61P781-21 06.03.1 SLS3 ..: P-8V87

Example 15

Synthesis of N - [(4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-dimethylaminocarbonyl-2-pyrimidinsulfonamide 6.2 g of 2-amino-4,6-dimethoxypyrimidine was added to 145 g of a 1,2-dichloroethane solution containing 4% phosgene at 15 ° C, and the solution was stirred. After stirring for about 10 minutes, a mixture of a solution of 18.2 g of triethylamine and 7.4 g of beta-picoline was added dropwise at 20 ° C, and the solution was reacted at room temperature for 30 minutes. The reaction solution was added dropwise to a suspension of 8.7 g of 2-aminosulfonyl-N, N-dimethyl-nicotinamide and 30 g of 1,2-dichloroethane at room temperature, and was reacted for 30 minutes.

After completion of the reaction, the product was extracted with 240 ml of water. The extract was converted to acidic solution with sulfuric acid and the precipitated crystals were graded. The crystals were washed with water and dried to give 13.3 g of the desired compound. ISHIHARA SANGY0 KAISHA Ltd., represented: —-----— 51 (Table 3, continued with p.50) 8 H 3 ch3 σι2σ > 3 2 οαΐ-, och3 171.5-173.5 9 5-a II II ch3 tl II tl 152-155 10 H n H phenyl II II II 188-190 11 4,6- (CH3) 2 lf ch3 ch3 II It tt 201-204 12 5-01,6-00¾. It II It tl It tl 166-168 13 H 11 H CELjCSCH. II tl II 154.5-157 14 »1 II - (CH2) 4“ It II II 158-162 15 6-C1 It čh3 ch3 It tt 11 183-186 16 H II II cooch3. tl tl It 162-164 17 6-OC2H5 It It ch3 It tl II 208-209 18 6-C2H5 tl tl It tl II II 193-194.5 19 6-CEL, OC & < . J II tl tl 11 II It 183-185 20 4,6- (CH3) 2 tl H tt tl It tl 179-181 21 6-F II ch3 II tl It II 115-124 22 6-Br It H C2H5 II II II - 23 6-CH3 II ch3 C3H7 (n) 11 II It - 24 6 —C £ 1 n II CH3 II ch3 It J_— 52 (Table 3, continued with p. 50) 25 H 3 H ch3 2 OfT-T * OCE3 147-149.5 26 II M II C2H5 II tl II 163-168 27 II II II C3H7 (iso) II II n 166.5-168.5 28 6-C2H5 II II CK 3 If tl II 29 H II ch3 II II II tl 169 -173 30 6-C3H7 (iso) tl II It II II It 31 6-1 It II If II It II 32 H II C2H5 C2h5 II ch3 tl 33 ff II ch3 II II 0CK3- It 170.5-172 34 6-CH3 II II ch3 II II 11 170-174 35 6-oa-v II It II II tl II 206-207.5 36 5-chf2 tl II II II II II 37 H tl C2H5 c2h5 II II tt 109-111 38 6-CH3 It H · Ch3 It I «It 183-185 39 6-CF3 M CH3 II II II II / 89 ~ / ff 40 6-Br II II c2h5 II II« 1 '- 41 6-N (CH3) 2 II II ch3 K II «1 199-201.5 1 53 (Table 3, continued with p.50) 42 6-SCF.3 3 CH3 CtT 2 OCH3- OCH3 200-201.5 43 H tl 1« 11 II ch3 11 177-185 44 6-NHCH3 11 11 11 tl och 3 It 183-185. 45 6-Br 11 tl It tl II II 201.5-203.5 46 H II II • 1 II II oc2h5 111-114 (decay) 47 11 II H! CK2) 3CH3 II II och3 156-158 48 6-CH2F 11 ch3 ch3 11 II II 180-181 49 6-CHF2 II • II tl tl 11 It 194-195 50 H II II 2,4-Difluorophenyl 11 II II 156-158 51 11 II II 4-Chloro-phenyl 11 II 11 241- 243 52 Pyridine N-oxide of the compounds Fo.29 169.5-171 53 6-CF3 3 ch3 C2H5 2 OCH3 OCH3 - 54 6-CH2OCH2CF3 11 II ch3 II II II 179-180 55 H 2 II II 3 II II 196-198 56 n 4 H tl II II II 129-132 57 1 «2 II • 1 M It II 122-125 58 6-OCK ^ CF-, ^ J 3 ch3 II 2 II 11 186.5-189 54 jfE & flash 3, continued with p.50) '* 59 Sodium salt of compound No.29 195-215 (decomposition) 60 Jlonomethylanine salt of compound No.29 125-128 61 Pyridine N-oxide of compound No.34 163-164.5 62 Potassium salt of compound No.25 - - 63 6-1 3 H CH3 4m OCH3 0 0 | i < i 1 ω 1 - 64 6-CF3 tl It II II It II - 65 6-CH3 tl ch3 c2h5 It • 1 II - 66 6-Br It H ch3 II • 1 II - 67 6-CA It tl It II II It - 68 6-CHF2 II It II II II II - 69 Sodium Compounds No.15 70 Sodium Compounds No.25 71 Sodium Compounds No.34 72 Sodium Compounds No.45 73 Sodium Compounds No.45 74 Dimethylamine Compounds No.34 55 -

The compounds of the present invention exhibit herbicidal effects against various weeds: Cyperaceae-type weeds such as rice mash (Cvperus iria), Japanese vesicle (Scirpus juncoides), and purple mash (Cyperus rotudus); graminous weeds (Gramineae) such as rural grass (Echinochloa crus-galli), common weeds (Digitaria adscendens), green fly (Setaria viridis), ash (Eleusine indica), wild oats (Avena fatua), Johnson grass (Sorghum halepense) , and lying grass (Agropyron repens); and broadleaf weeds such as spleen (Abutilon theophrasti), low hulk (Ipomoea purpurea), common ash (Chenopodium album), bottle (Sida spinosa), common defiance (Portulaca oleracea), thin amaranth (Amaranthus viridis), sickle root (Cassia root) bark (Solanum nigrum), water pepper (Polygonum longisetum), common mussel (Stellaria media), common thistle (Xanthium strumarium), and humpback (Cardamine flexuosa).

Therefore, the hebicides of this invention will find application such as in farms and agricultural fields, for example / wells and mulberry trees and non-agricultural fields, for example forests, alleys, playgrounds, hippodromes, parks. The herbicidal compositions of the present invention can be applied by treating the soil or treating the leaves, if desired. 56

The compounds of this invention in particular can have herbicidal effects against harmful weeds in cereals and can be used effectively. The herbicidal compound of the present invention is administered in the form of granules, wettable powder, emulsifiable concentrates or aqueous solutions prepared by mixing the compound with a carrier as well as with additives such as a diluent, solvent, emulsifier, nebulizer or surfactant, as appropriate. Suitable mixing ratio of the active ingredient to agricultural additives ranges from 1: 99 to 90: 10 and preferably from 5: 95 to 60: 40 by weight. The optimum amount of active ingredient used cannot be absolutely determined as it varies depending on various factors such as climatic conditions, weather conditions, soil conditions, chemical form, type of weeds to be controlled, or duration of application, but the amount of active ingredient is usually from 0.1 to 100 g per acre, preferably from 0.2 to 50 g, and more preferably from 0.5 g to 10 g.

The herbicidal composition of the present invention can be mixed or used together with other agricultural chemicals, fertilizers, soil or protective agents. Such applications give approximately the same or better effects or effects. Examples of other herbicides that can be mixed with the herbicidal composition of the present invention are listed below. In some cases synergism can be ascertained. 57 3,6-Dichloro-2-methoxybenzoic acid 2.5-dichloro-3-aminobenzoic acid (2,4-dichlorophenoxy) acetic acid (4-chloro-2-methylphenoxy) acetic acid 2-chloro ~ 4,6-bis (ethylamino) ) -1,3,5-triazine 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine 2- (4-chloro-6-ethylamino-1,3,5-triazin-2-ylamino) ) -2-methylpropionitrile 2-ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine '2-chloro-21,6'-diethyl-N- (methoxymethyl) acetanilide 2-chloro-61-ethyl- N- {2-methoxy-1-methylethyl) aceto-o-toluidide 2-chloro-N-isopropylacetanilide 2-chloro-N, N-di-2-propenylacetamide S-ethylenedipropylthiocarbamate S-ethylenedi-isobutylthiocarbamate N-propyldropropylthiocarbamate N- (2) 1-ethylpropyl) -2,6-dinitro-3,4-xylidine alpha, alpha, alpha-trifluoro-2,6-dinitro-N, N-dipropyl p-toluidine 2- (3,5-dichlorophenyl) -2- (2,2,2-trichloroethyl) oxirane 3- isopropyl- (1H) -benzo-2,1,3-thiadiazin-4-one-2,2 'dioxide 3- (3,4-dichlorophenyl) -1-methoxy -1-methylcarbamate 3,5-dibromo-4-hydroxybenzonitrile 2-chloro-4-trifluoromethylphenyl-3-ethoxy-4-nitro-phenylether. 58

For example. N / (4/6-dimethoxypyrimidin-2-yl) -aminocarbonyl / -3-methylaminoacarbonyl (or dimethylamino-carbonyl) -2-pyridinsulfonamide, or 6-chloro (or bromo-, difluoromethyl- or methyl-) - N- / (4,6-Dimethoxypyrimidin-2-yl) aminocarbonyl-3-dimethylaminocarbonyl-2-pyridine sulfonamide can be used in combination with 2-chloro-4-ethylamino-6-isopropylamino-1, 3,5-triazine, 2- (4-chloro-6-ethylamino-1,3,5-triazin-2-ylamino) -2-methylpropionitrile, 2-chloro-2 ', 6'-diethyl-N- (methoxy-methyl) acetanilide, 2-chloro -6'-ethyl-N- (2-methoxy-1-methylethyl) aceto-o-toluidide or N- (1-ethoxypropyl) -2,6-dinitro-3,4-xylide. The herbicide of this combination is not harmful to cereals and allows the killing of weeds almost completely.

Test case 1

Parcels of 1/1, 500 acres were supplied with surface soil and planted pre-determined seed quantities of different plants for testing. When test plants have reached a predetermined growth rate (ie 2.2- to 3.5-leaf stage for corn (Zea mays), 2.0- to 3.5-leaf stage for wheat (Triticum aestium), 2.0- to 3.5-leaf stage for common bottle, 0.5- to 1.2-leaf grade for low logging, 0.5- to 1.2-leaf grade for water pepper, 0.1- to 1.5-leaf grade for - 59 - slender amaranth, and 2.0- to 2.5-leaf grade for rural grass) , an aqueous dispersion was prepared by diluting the wettable powder containing a predetermined amount of each test compound with 5 l / ar water, and 0.2% of the agricultural spray was added to the aqueous solution. The resulting solution was applied to the leaves of small spray plants. Twenty-two or thirty-seven days after application, the plant's growth rate was visually observed. Weed control is expressed on a 10-point scale where 10 indicates that the plant has been completely destroyed and 1 indicates that there was no effect, as shown below in Table 4. 60

Day view < 0 • c (C «n on the 25th day of the 28th day of the 25th day of the 28th day of the 28th day of the 24th day Weed control Rural grass 10 r- CO CO ID m 10 10 in cn 10 VD Thin Amaranths 1 r- in r ~ in CD ID co VD 10 r- 10 01 r- r- Water CD CD r ~ m σ \ ω " 3 * CD co 10 P 'Bottle in r- in and r - ID iD CO ID ID co Niš lado- bed σ \ r > · co ID σ \ ID cn cn CT »r ~~ cn σ \ VD Plain Velcro 10 | 10 C \ σ \ ID 10 cn 00 r- 10 10 10 < Ti Wheat σ \ Γ 'n (N in rH σι n rH ID r ID Kuku- ruz H rH rH rH rH »—H rH rH rH rH rH rH rH rH Amount of active ingredient (g / a) tn • 1.25 in 1.25 and 1.25 and 1.25 in m (N * rH in and CN • rH and 1.25 Joining Ho. RH CM mm VD Γ- 61

By son-shit days 24. on 28 ·.! on 37. on 37. on 28. on 37 ·. days 28 · days Weed control Farmland Γ " r * 10 10 1 1 1 1 CTi t " CJ \ CTV 10 CO Thin amaranth and 10 10 10 co 0T 1 10 1 1 10 CO 10 σ \ 10 σ \ Water biber ___1 Γ " vo σι 1 10 r ~ 10 σ \ 10 σ > 10 10 CDs I " Bottle m CO 1 • m 1 lO ID and 1 m CO t " Niš Lado-axis Os r * 10 CO co CO 10 cn 1 10 10 10 cn 10 co Ordinary Velcro cr »σ 10 10 10 o rt 10 10 10 10 10 op — 4 as co υ -HC, d) a, U3 in 10 en rH CO and CD Γ " σ \ σι as co Kuku- ruz rH rH «H rH fH ri rH lH rH rH rH rH CM rH (0 cr n? • HC 'n xj > om • H -H 4J' v. H4J Ul C. 0 M Λ * - «(0« m in cm • H m 1.25 mm CM • rH m 1.25 m in (NJ • pH m U) CM • rH m 1.25 Jedi-n yen is No. 1: co o \ 10 11 IN rH 13 14 62 4

Stripping - day shaking • «J He c (N '< 0 Ό 28th day 28th day 28th day · 25th day 37th day · 28th day Control corp. Rural grass O rH 10 r - NO CO m 03 10 10 r- in 10 10 Thin amaranth 10 01 00 NO a \ cn 10 10 01 10 O rH CT »10 o rH Water biber 10 10 ON 03 10 10 I 10 10 1 10 ON ON 10 10 r · Bottle ON NO CO NO NO NO NO TJ ON r · vo and KD m Niš lado- bed ___ ^ _ O i — l 01 ON r- 1 10 10 | ON σ \ 10 10 10 σ \ 10 σ \ Common Velcro 10 10 ON CO 10 10 10 10 01 10 10 rc- 10 (0 o •• HC o yn cu 10 10 ON v rc- r- 1 1 10 10 10 tn j 1 ί MN 3 3 XU i — t » —Ι rH i — l rH r — 1 r — IH r — 1 r — 1 rH rH rH i * -H < 0 (CC 0 ^ -. -H c: -n as > c f > 0 ^ • H · Η + J ¢ 7 --1 + J tn - 0 X as as as in 1.25 and 1.25 | in 1.25 and 1.25 m and CN • * —1 m 1.25 m and t > j • rH Jedi-n yen is No 15 1 1 16 17 18 19 20 21 63 π ί CPW Ol.tCl - Daybreak • O r > days 24 - days 24 - 24 · days • (0 m S ^ Ό 25 · days 24. Control weeds Rural grass 10 o H 10 cn 10 cn σι 1 10 Ο rH 01 10 σι 10 σ \ Thin unarant 10 10 < 7i d 10 CO σ \ 10 01 σ \ Ο ι — 1 10 10 10 Water Diberka 10 10 00 r »00 σι CO σ \ σι 10 10 ο rH 10 Bottle 10 r · 'r- r > f »r- σι Γ " σ \ 00 σι 00 r »m Niški Ladolež 10 σι 10 r- co 00 σι 00 σι < η σ \ σ \ 10 σι Common thistle 01 10 10 σ \ 10 r ~ σ» 10 01 10 10 10 10 σι Wheat 10 00 00 00 r * MO '10 CO Ο »H os 10 10 10 Corn - iH l“ H rH r — i • Ή iH < Ν ι-Η CN Γ-Η ι-Η rH ιΗ (0 & > (0 'C 0 X • H c -ΓΊ (0 Λ > > 0 \ • H -rl ci rt 4J 0) oxn}' X, < 0 m and 1.25 m 1.25 in i 1.25 ιη m < Ν • Η m 1.25 m 1.25 m 1.25 Joining Ho 25 26 27 29 m η 34 35

- 64 -

Posrination on 28. on 28. on 31. days 28 ... days 22 .. days 22. on 29. . on rt > 0 µ 0 j * Π3 rH 0 µ -P c 0 Rural grass. σ \ d 10 < n 10 σ \ 00 νο Γ " r- 10 cn 10 10 Thin amaranth 10 10 10 σ 10 10 I! 10 ο rH 00 co σ σι 10 Water Diberka 03 co 10 σ 10 10 10 10 co r- 10 σ 10 σ Bottle VD VD < Ti VD σ C0 10 10 m co r- Γ " VD i- Nis shipyard CTi FROM 10 σ 10 σ \ σ σι r- r * o rH r- ~ σ σ Common Velcro 10 σ \ 10 10 10 10 10 [10 00 r ~ 01 10 10 10 Wheat m ιο 00 σ 1 10 ω II 1 1 '1 10 10 Kuku-- ruz rH rH rH rH co • Ή “t rH CN r — 1 CN rH rH rH Amount of active ingredient (g / a > in [| 1.25 i in 1.25 ΙΛ 1.25 ιη 1.25 m and (N • H m 1.25 and 1.25 1 d) • H -n · Ό C 0 d) 0) at, · π C 37 4 co m 41 42 43 44 45 65 fc

Observation on the day 29 ·. on 25. on 26. days and 1 29. days 29 '. on 36. · On day 36 '. days Weed control Rural grass 1__ οτ σ \ in in 10 10! 10 01! ID m 10 10 10 and Thin Amaranth O • H 10 r »and 10 r- ~ 10 € Ti Γ 'ID 10 σι CO and Water Pepper 10 c \ ID " SP o« H 10 σ \ < n r- CT »Σι vn and Boca r > in and nj ID m Γ 'VD ro «cT ί *. % • ri M 0 cfl 13 'Ά (¾ 2 Ή σι σ \ o \ r- ~ σι r «10 01 ID in σ \ CD 10 r- Plain Velcro' r ~ in 10 a \ 10 co 10 01 1 10 10 σ \ σ \ σ \ σ \ Wheat 01 and C \ r ~ J 1 10 o 1 10 «3 * 1 • 1 1 Maize rH» -H »- < (N • —H r-4 r — t ι - i H mr - i Amount of active ingredient (g / a) in 1.25 m 1.25 in 1.25 in in ΓΜ • r-4 in 1.25 in 1.25 in 1.25 Unit is No. 46 47 48 49 50 52 54 66

Observation of Day 28. days • (0 • C in cm TI on day 28 on day 22 on day 24. · c CM TS Weed control Rural grass -co co KO VO 10 σ r ~ 10 10 Thin amaranth o 1 cn Γ '10 | 10 m CO 10 10 Water pepper σ 1 σι 00 10 σ co ID cn < n Bottle 1 co KO σι co (N rH io m Niš Shipyard 10 10 σι co 10 10 cn CO 10 cn Ordinary Velcro 10 10 σ \ r ~ 10 σ 10 cn 10 σι Wheat cn CO ΙΟ * < r 1 1 10 10 1 d λ: ndd «u • H rH rH rH " 3 ·» H pH rH H rH Amount of active ingredient (cr / a) and 1.25 and 1.25 in 1.25 m 1.25 in CN • rH 1.25 Saving No. 55 56 57 58 59 09 - 67

Test case 2

The 1 / 10,000-acre plots, respectively, are supplied ♦ with land, and are planted with ordinary weeds and black velvet. Subsequently, when the tested samples of common weeds and corms reached 2- and 0.5-leaf degrees, respectively, the compound to be used was measured by determining the content of the active ingredient previously, and the compound was diluted in 5 l of water per acre. To this aqueous solution was added 0.2% of the agricultural sprayer, and the resulting solution was sprayed with a sprayer. The growth rate of ordinary weeds and weeds was visually checked after 23 days, and weed control was expressed in the same way as in Test Example 1. The results are shown in Table 5.

Table 5

Compound No. Amount of active ingredient (g / a) Weed control Ordinary weed Black remark 25 5.0 8 10 2.5 7 10 29 5.0 10 10 2.5 10 10 68

Test case 3

Two 15 cm long roots * " Johnson grass " are planted on a plot of 1/3000 acres in a glass garden. When the grass reached the 4- to 5-leaf stage, the compounds to be used were measured to take a predetermined amount, and the compounds were diluted with 5 liters of water per acre. In addition, 0.2% of the agricultural sprayer was added to this aqueous solution, and the resulting solution was sprayed on the leaves and stems of the plants. Thirty-five days after application, a visual inspection of the weeds of this grass was carried out. Weed control was expressed in the same manner as in Test Example 1 'and the results are shown below in Table 6.? - »C novices 69 5 10 15

Table 6

Jdininje No. Amount of active ingredient Weed control 25 5.0 9 2.5 8 ~ 9 1.25 7 0.625 4 29 2.5 9 ~ 10 1.25 9 ~ 10 0.625 8 ~ 9 0.313 7 34 2.5 9 1.25 9 0.625 8 0.313 6 ~ 7

Testing Example 4 The four sprouted roots of a purple vellum were planted on a parcel of 1 / 10,000 acres in a glass garden. When the stock reached a 3- to 4-leaf stage, the compounds to be used were measured by determining the active ingredient content previously, and the compounds were diluted with 5 liters of water per acre. In addition, 0.2% of the agricultural spray was added to this aqueous solution and the resulting solution was sprayed on the leaves of the plants. 70

Fifty-one days after application, weeds were visually inspected for purple purple. h

Weed control was expressed in the same way as in Test Example 1, and the results are shown below in Table 7.

Table 7

Compound No. Amount of active ingredient (g / a) Weed control 5.0 10 15 2.5 10 1.25 10 0.625 10 5.0 10 21 2.5 10 1.25 9 0.625 8 2.5 10 29 1.25 10 0.625 10 0.313 8. 5.0 10 34 2.5 10 1.25 10 0.625 9

Examples of formulations of herbicidal compositions of the present invention will be described below. 71

Formulation Example 1 k parts by weight (1) Kaolinite Powder 97 (2) Polyoxyethyleneoctylphenyl ether 2 (3) Compound No.15 1

The ingredients above are mixed and powdered.

Example formulation 2 parts by weight (1) Starch soluble in water 55 (2) Sodium lignosulfonate 5 (3) Compound No.59 40

The above ingredients are mixed and dusted to make an aqueous solution.

Example formulation 3 parts by weight (1) Kaolin 78 (2) Condensation product of sodium naphthalenesulfonate and formalin 2 (3) Polyoxyethylenealkylallylethanesulfonate 5 (4) Micro-powdered silica 15

Ingredients (1) to (4) were mixed with the compounds of the invention at a 9: 1 mixing ratio to give a yeast powder.

Example formulation 4 * parts by weight (1) Diatomic acid 63 (2) Polyoxyethylenealkyl-phenylethersulfate ammonium salt with 5 (3) Dialkylsulfosuccinate 2 (4) Compound 29

The above ingredients are mixed and a yeast powder is formed.

Example formulation 5 parts by weight (1) Micro-powdered talc 33 (2) Dialkyl sulfosuccinate 3 (3) Polyoxyethylenealkyl sulfate 4 (4) Compound No 34 60

The ingredients above have been mixed to prepare the yeast powder.

Example formulation 6 parts by weight (1) Sodium phenylsulfonate 4 (2) Sodium polycarboxylate 3 (3) Sodium alkylarylsulfonate 1 (4) Kaolin 12 (5) Compound No.25 80

The above ingredients are mixed with added water, after drying they are disintegrated and a wettable powder is formed

DOS.2036 CYR-61P781-21 12.04.1988. P-87/87 ^ c

APPLICANT'S STATEMENT ABOUT THE BEST IT'S MODE-2 *: ECONOMIC USE OF THE APPLICATION FOUND

Synthesis of N - [(4,6-dimethoxypyrimidin 2-yl) aminocarbonyl] -3-dimethylaminocarbonyl-2-pyridine sulfonamide

A mixture of a solution of 250 mg of 2-amino-4,6-dimethoxy-pyrimidine, 0.65 g of triethylamine, and 2.5 g of ethyl acetate was added dropwise to 6.9 g of ethyl acetate solution containing 20% phosgene at 15 ° C, and the mixture was maintained at 15 ° C and reacted for one hour. The mixture was then heated to 90 ° C in an oil bath and the excess phosgene and ethyl acetate were distilled off. A solution was then prepared by dissolving 300 mg of 2-raminosulfonyl-N / N-dimethyl-nicotinamide in 10 ml of acetonitrile, which was added dropwise to the above mixture, and 0.2 g of triethylamine was then added dropwise. The resulting mixture was reacted at room temperature for one hour.

After completion of the reaction, the product was added to water-acidified with hydrochloric acid and the precipitated crystals were graded. The crystals were washed with water and dried to give 0.4 6 g of the desired product.

• /

Claims (1)

. I. And 'Q \! P-87/87 in /.-.* · 06.03i 1990AN '? ·: ·; • j r '• i' «· Dos.2036 CYR-61P781-21 / PATENT REQUIREMENT A process for the manufacture of a substituted pyridine sulfonamide compound · > —n-jpgnvo soU- ^ represented by the following costly formula: P.-SO-jNHCONH (D 0 Rl • Rl in which R represents a CN (Y) n n group or Oj-R2 - - (Y) n O, CN R2 wherein each of R1 and r2 independently represents a hydrogen atom, a C 1-6 alkyl group, a halo- A C 1-6 alkyl group, a C 2-5 alkenyl group, a C 2-8 alkynyl group, a C 1-6 alkoxy group, a halo-C 1-6 alkoxy group, a C 1-6 alkoxy-C 1-6 alkyl group, a halo-C 1-6 alkoxy-C 1-6 alkyl group, a C 1-6 cycloalkyl group, a halo- A C1-6-cycloalkyl, C., alkoxycarbonyl, halo-C, alkoxycarbonyl group, a phenyl group or a halophenyl group, provided that when one of R1 and r2 represents a hydrogen atom, the other represents one of the groups except the hydrogen atom; R1 and R2 together with the 'adjacent nitrogen atom can form a heterocycle; Y represents a halogen atom, a C 1-6 alkyl group, a halo-C 1-6 alkyl group, a C 1-6 alkoxy group, a halo-C 1-6 alkoxy group, a C 1-6 alkyl-thio group, a halo-C ^ an alkylthio group, a C 1-6 alkoxy-C 1-6 alkyl * __- R '' group, a halo-C 1-6 alkoxy-C 1-6 alkyl group or a group (where each of R 3 and R 4 represents a hydrogen atom or C 1-6 alkyl); - n represents Ο or the integer 1 or 2; ~ -and each of χ 1 -Λ λ2 independently represents a methyl group, methoxy "and a group'or-ethoxy group, comprising the reaction of a pyridine compound represented by the following general formula: R - S07Z1 in chloro R has the meanings given above, Z1 represents NH0 group, -NCO group, -KHC0C1 group or -NHCOOR ^ (where R5 represents C 1-6 alkyl or phenyl group) with the pyrimidine moiety represented by the following general formula: in which each of X3 and X4 independently represents a halogen atom, a methyl group, a methoxy group, 'or an ethoxy group, 22 represents a -NH2 group -NCO group, -NHC0C1 group or -NHCOOR- (where R5 has the meanings given above), provided that when Z1 represents the NH2 group, Z2 represents the -NCO group, -NHC0C1 group or -NHCOORc- group, and when Z2 predisposes the NH2 group, Z1 represents -NCO group, -NKC0C1 group, or -NHCOOR- group; then performing methoxylation or ethoxylation when X 3 and / or X 4 represents a halogen atom, at a temperature of 20-100 ° C and in a solvent selected from nitriles such as acetonitrile, ethers such as dioxane and. cyclic or acyclic aliphatic hydrocarbons such as 1,2-dichloroethane; after which the resulting compounds are converted into their salt as needed. ISHIHARA SANGYO KAISHA Ltd., i