ES2352819T3 - PROCEDURE FOR THE PRODUCTION OF A SUBSTITUTED ANILINE COMPOUND. - Google Patents

Abstract

Process for the production of a substituted indole compound represented by the following general formula (3): ** (See formula) ** (in the formula, R1, R2 and R3 are each independently an alkyl group, an alkoxy group, a alkoxyalkyl group, a haloalkyl group, a carboxyl group, an alkoxycarbonyl group, an alkylcarboxamido group, a nitro group, an aryl group, an arylalkyl group, an aryloxy group, a halogen atom or a hydrogen atom; and X and Y are each independently a hydrogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a haloalkyl group, a carboxyl group, an alkoxycarbonyl group or a halogen atom), characterized in that it comprises reacting, in the presence of an acid, a compound of (pyrimidin-2-yl) -2-propanone represented by the following general formula (1): ** (See formula) ** (in the formula, R1, R2 and R3 are defined as above), with a hydrazine compound represented by the s following general formula (2): ** (See formula) ** (in the formula, X and Y are defined as above).

Description

[0001] The present invention relates to a process for the production of a substituted indole compound, which may become an intermediate compound useful in the production of an aniline compound which, again, may become a compound intermediate useful in the production, for example, of agricultural chemicals and medicines.

[0002] It is already known that some sulfonanilide derivatives containing 4,6-dimethoxypyrimidine have a high herbicidal activity (see JP-A-11-60562 and WO 00/06553). It is also known that, in its production, a substituted aniline compound is useful as an important intermediate compound. [0003] Meanwhile, they have already been described (see JP-A-7-48359, WO 96/41799)

15 processes for the production of a substituted aniline compound which is an important intermediate compound for sulfoanilide derivatives having a high herbicidal activity. These procedures each use a reaction that is disadvantageous in its industrial application; therefore, it has been desirable to be able to develop a procedure that can produce in the industry, so

20 advantageously, the desired substituted aniline. [0004] Henry, J.R. et al., "Potent inhibitors of the MAP Kinase p38", Bioorganic and Medicinal Chemistry Letters 8 (1998), 3335-3340 describe substances that can serve as potent inhibitors of MAP kinase p38 and its synthesis. In this regard, possible preparations of suitable substituted indole compounds are described

25 for this application. [0005] The present inventor carried out a study in order to solve the above problem. As a result, it was found that a desired substituted aniline compound can be produced by reaction, for example, of a (pyrimidin-2-yl) -2-propanone compound with a hydrazine compound in

The presence of an acid, to produce a substituted indole compound, oxidation of the substituted indole compound to give rise to the indole ring and thus obtain an acetanilide compound and subject the acetanilide compound to reduction preferably with sodium borohydride or to deacetylation of the half amide, that is, the above problem can be solved. This finding has

5 led to the development of the present invention.

Best way to carry out the invention [0006] The present invention is described in detail below. [0007] Consequently, the above problem has been resolved primarily at through the following invention.

[0008] A process for the production of a substituted indole compound represented by the following general formula (3):

image 1

(in the formula, R1, R2 and R3 are each independently an alkyl group, a

alkoxy group, an alkoxyalkyl group, a haloalkyl group, a carboxyl group, an alkoxycarbonyl group, an alkylcarboxamido group, a nitro group, an aryl group,

an arylalkyl group, an aryloxy group, a halogen atom or an atom of

hydrogen; and X and Y are each independently a hydrogen atom, a

alkyl group, an alkoxy group, an alkoxyalkyl group, a haloalkyl group, a

carboxyl group, an alkoxycarbonyl group or a halogen atom), characterized in that it comprises reacting, in the presence of an acid, a compound of

(pyrimidin-2-yl) -2-propanone represented by the following general formula (1): (in the formula, R1, R2 and R3 are defined as above), with a hydrazine compound represented by the following general formula (2 ):

image 1

image 1

(in the formula, X and Y are defined as above).

[0009] The present invention is described in detail below. [0010] The substituted indole compound represented by the general formula (3) can be produced by reacting, in the presence of an acid, a (pyrimidin-2-yl) -2-propanone compound represented by the general formula (1) with a hydrazine compound represented by the general formula (2). Therefore, the

The description is carried out on the basis of a step for the production of a substituted indole compound represented by the general formula (3). [0011] First, the description is made based on the (pyrimidin2-yl) -2-propanone compound represented by the general formula (1) and based on the hydrazine compound represented by the general formula (2), used both as materials

15 starting. [0012] In the compound of (pyrimidin-2-yl) -2-propanone represented by the general formula (1), R1, R2 and R3 can each independently be an alkyl group of 1 to 6 carbon atoms (hence hereinafter, carbon atoms, when they are, for example, 1 to 6 carbon atoms, are abbreviated as "C1 to C6") straight chain

Or branched, such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, a tert-butyl group, a npentyl group, an n- group hexyl or the like; a C1 to C6 straight or branched chain alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group or the like; a (C1 to C6) alkoxy straight chain (C1 to C6) alkyl group

Or branched, such as a methoxymethyl group, a methoxyethyl group, an ethoxyethyl group or the like; a straight or branched C1 to C6 haloalkyl group, such as a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group or the like; a carboxyl group; a linear or branched (C1 to C6) alkoxy group, such as a methoxycarbonyl group, an ethoxycarbonyl group or the like; a linear or branched (C1 to C6) alkyl carboxamide group, such as a methylcarboxamide group, an ethylcarboxamide group or the like; a nitro group; an aryl group, such as a similar phenyl group; an arylalkyl (C1 to C6) group of

Straight or branched chain such as a phenylmethyl group, a phenylethyl group or the like; an aryloxy group such as a phenoxy group, a naphthoxy group or the like; a halogen atom, such as a bromine group, a chlorine group, a fluorine group, an iodine group or the like; or a hydrogen atom. [0013] Therefore, as the (pyrimidin-2-yl) -2-propanone compound represented

10 by the general formula (1) that can be used in step 1, they can be specifically mentioned, for example, 1- (pyrimidin-2-yl) -2-propanone, 1- (4,6-dimethylpyrimidin-2- il) -2-propanone, 1- (4,6-dimethoxypyrimidin-2-yl) -2-propanone, 1 (4,6-dimethoxy-5-methylpyrimidin-2-yl) -2-propanone, 1- (4 , 6-dimethoxy-5-ethylpyrimidin-2-yl) -2-propanone, 1- (4,6-dimethoxy-5-nitropyrimidin-2-yl) -2-propanone, 1- (4,6

Dichloropyrimidin-2-yl) -2-propanone, 1- (4,6-dimethoxy-5-ethoxycarbonylpyrimidin-2-yl) -2propanone, and 1- (4,6-diethoxypyrimidin-2-yl) -2-propanone . The (pyrimidin2-yl) -2-propanone compound represented by the general formula (1) has tautomers and any of the tautomers can be used in the process of the present invention. However, in the present description, the structure of the compound is

It is expressed as the 2-propanone derivative as seen in the general formula (1) and the nomenclature of the compound is carried out as a 2-propanone derivative as indicated above. [0014] These (pyrimidin-2-yl) -2-propanone compounds represented by the general formula (1) are known compounds or compounds that have been

25 produced using as a material such as 2-phenylsulfonyl-4,6-dimethylpyrimidine or the like according to, for example, the procedure described in Chemical & Pharmaceutical Bulletin, p. 152 (1982). The (pyrimidin-2-yl) -2-propanone compound represented by the general formula (1) includes new compounds, for example, 1- (4,6-dimethoxypyrimidin-2-yl) -2-propanone and this compound is a

30 useful starting material in the production of the substituted aniline compound

-5 represented by the general formula (6). [0015] Meanwhile, in the general formula (2), X and Y can each independently be a straight or branched C1 to C6 alkyl group, such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a

N-butyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an n-hexyl group or the like; a C1 to C6 straight or branched chain alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group or the like; a (C1 to C6) alkoxy group (C1 to C6) straight or branched chain alkyl, such as a methoxymethyl group, a methoxyethyl group, an ethoxyethyl group or

10 similar; a straight or branched C1 to C6 haloalkyl group, such as a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group or the like; a carboxyl group; a linear or branched (C1 to C6) alkoxy group, such as a methoxycarbonyl group, an ethoxycarbonyl group or the like; a halogen atom, such as a bromine group, a chlorine group, a fluorine group, a group

15 iodine or the like; or a hydrogen atom. [0016] Therefore, as the hydrazine compound represented by the general formula (2) that can be used in step 1, there can be specifically mentioned, for example, phenylhydrazine, 2-methylphenylhydrazine, 4-methylphenylhydrazine, 2, 4-dimethylphenylhydrazine, 2-ethylphenylhydrazine, 4-ethylphenylhydrazine, 4

20 isopropylphenylhydrazine, 2-methoxyphenylhydrazine, 4-methoxyphenylhydrazine, 2-methoxymethylphenylhydrazine, 4-methoxymethylphenylhydrazine, 4-trifluoromethylphenylhydrazine, 2-hydrazinobenzoic acid, 4-methoxycarbonylphenylhydrazine and 2-chloropherazine. [0017] The hydrazine compound represented by the general formula (2) may be in the free form or in the salt form (for example, a compound a

25 hydrochloride or sulfate). [0018] The hydrazine compound represented by the general formula (2) is a known compound or a compound that can be produced using the corresponding aniline as a starting material according, for example, to the procedure described in the Journal of Organic Chemistry, p. 2849 (1972).

[0019] Incidentally, among the various hydrazine compounds

-6 represented by the general formula (2), 2-methoxymethylphenylhydrazine is a new compound. [0020] In the production step of a substituted indole compound represented by the general formula (3), the molar ratio of the hydrazine compound represented

5 by the general formula (2) with respect to the compound of (pyrimidin-2-yl) -2-propanone represented by the general formula (1) can be in any range that allows the reaction between the two compounds to be carried out. However, the (pyrimidin-2-yl) -2-propanone compound represented by the general formula (1) is used in an amount of, for example, conventionally 0.5 to 3 moles, with

Preference 1 to 2 moles per mole of the hydrazine compound represented by the general formula (2). [0021] The production step of the substituted indole compound represented by the general formula (3) is carried out using an acid. The acid that can be used can be exemplified by mineral acids, such as hydrochloric acid,

15 sulfuric acid and the like; acetic acids such as acetic acid, trifluoroacetic acid and the like; Lewis acids such as zinc chloride, boron trifluoride and the like; sulfonic acids such as p-toluenesulfonic acid and the like; phosphoric acids such as polyphosphoric acid and the like; phosphorus halides such as phosphorus trichloride and the like; and acidic ion exchange resins such

20 as Amberlist and the like. The use of a Lewis acid such as zinc chloride, boron trifluoride or the like is preferred. The amount of the acid used in the step may be any amount as long as the substituted indole compound formed represented by the general formula (3) does not decompose; however, it may be 0.001 to 10 moles, preferably 0.1 to 2 moles per mole of the

25 hydrazine compound represented by the general formula (2). [0022] The production step of the substituted indole compound represented by the general formula (3) can be allowed to proceed sufficiently even in a solvent free state, but can also be carried out using a solvent. The solvent used in the present reaction can be any solvents as long as

30 as long as they do not harm the reaction. For example, they can be mentioned

aromatic hydrocarbons such as toluene, xylene, chlorobenzene and the like; halogenated aliphatic hydrocarbons such as dichloromethane, chloroform and the like; acetic acid esters such as methyl acetate, ethyl acetate, butyl acetate and the like; aprotic polar solvents such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone, tetramethylurea, hexamethylphosphotriamide (HMPA) and the like; ether solvents such as diethyl ether, tetrahydrofuran, dioxane and the like; and aliphatic hydrocarbons such as pentane, n-hexane and the like. Aromatic hydrocarbons such as toluene and the like are preferred. These solvents can be used alone or as a

10 solvent mixture in any mixing ratio. The amount of solvent can be found in any range as long as they can guarantee sufficient agitation of the reaction system, but usually it can be 0.5 to 20 liters, preferably 1 to 10 liters per mole of the hydrazine compound represented. by the general formula (5).

[0023] The reaction temperature employed in the step to [0024] Produce the substituted indole compound represented by the general formula

(3) is, for example, from 0 ° C to the reflux temperature of the solvent used, preferably from 0º C to 120º C. [0025] There is no particular limitation on the reaction time used

20 in the production stage of the substituted indole compound represented by the general formula (3), but preferably the time is 0.5 hours to 12 hours. [0026] The substituted indole compound represented by the general formula (3), which can be produced in the step, is a new compound and is useful as an intermediate compound for a sulfoanilide derivative known to have a high

25 herbicidal activity and because it is useful. [0027] Among the hydrazine compounds represented by the general formula (2), 2-methoxymethylphenylhydrazine can be produced using the corresponding aniline as the starting material according to, for example, the procedure described in the Journal of Organic Chemistry, p. 2849 (1972).

[0028] Similarly, among the (pyrimidin-2-yl) -2-propanone compounds represented by the general formula (1), 1- (4,6-dimethoxypyrimidin-2-yl) -2-propanone can be produced using a starting material such as 2-phenylsulfonyl-4,6-dimethoxypyrimidine or the like according to, for example, the procedure described in Chemical & Pharmaceutical Bulletin, p. 152 (1982). This

The compound has tautomers and all tautomers are included in the present invention. [0029] In addition, the substituted indole compound represented by the general formula (3) is a new compound and can be produced by the step described hereinabove. Incidentally, in the general formula (3), R1, R2, R3, X e

10 And they have the same definitions as those indicated above. [0030] In the following table 1, examples of the substituted indole compound represented by the general formula (3) are shown. However, the compound of the present invention is not limited to these and includes all the compounds represented by the general formula (3).

15 [0031] Incidentally, the symbols shown in Table 1 have the

following meanings (the same applies to the following tables). Me: methyl group Et: ethyl group MOM: methoxymethyl group

20 MeO: methoxy group EtO: ethoxy group i-Pr: isopropyl group COOMe: methoxycarbonyl group NO2: nitro group

25 CF3: trifluoromethyl group NHAc: acetamide group Table 1

Compound

X Y R1 R2 R3 Melting Point (º C)

3-1

H H OMe H OMe 182-184

3-2

I H I H I

3-3

H I OMe H OMe

3-4

H Et H H H

3-5

I I OMe NO2 OMe

3-6

H MeO OMe I OMe

3-7

EtO H OMe COOMe OMe

3-8

H MOM OMe H OMe 176-189

3-9

Cl H OEt H OEt

3-10

H F H NHAc H

3-11

H COOH Cl H Cl

3-12

COOMe H H MOM H

3-13

I COOMe H CF3 H

3-14

Cl I OMe H OMe

3-15

i-Pr H OMeH H OMe

3-16

Cl I OMe H OMe 179-181

3-17

i-Pr H OMe H OMe 156-158

3-18

H Et OMe R2 OMe 90-95

[0032] Next, the process for the production of the compound of the present invention is specifically described by way of examples. In the examples, the refractive index n20 D indicates a refractive index measured at 20 ° C 5 using a sodium D line. Gas chromatography was carried out using, as a column, G-250 (40 m) [a product from (Zai) Kagaku Busshitsu Hyoka Kenkyu Kiko (formerly, Kagakuhin Kensa Kyokai). High performance liquid phase chromatography was carried out using, as a column, YMCA312 (a product of K.K. YMC) and, as eluent, an aqueous solution of

10 acetonitrile / 0.05% phosphoric acid. Example 1 Production of 2-methoxymethylphenylhydrazine [0033] 6.86 g (50 mmol) of 2-methoxymethylamine was dissolved in 50 ml of concentrated hydrochloric acid. The solution was cooled to -10 ° C. To it was added.

15 then dropwise a solution of sodium nitrite (4.14 g, 60 mmol) dissolved in water (50 ml) while maintaining a temperature of -10º C to 0º C. At the previous temperature and for 1 hour it was then added drop by drop a solution of 44.6 g (235 mmol) of stannous chloride dissolved in concentrated hydrochloric acid (50 ml). Once the dropwise addition was completed, stirring was carried out with a

20 gradual increase in temperature to approximately 20 ° C. [0034] A 10% aqueous solution of sodium hydroxide was then added dropwise to obtain a pH of 14, after which the extraction with toluene was carried out. The toluene layer was washed with water and concentrated under reduced pressure using a rotary evaporator to obtain 5.40 g (35.5 mmol) of liquid 2-methoxymethylphenylhydrazine. Yield: 71%.

5 MS m / e: 152 (M +) 1H-NMR (CDCl3 / TMS), δ (ppm): 3.8 (s, 3H), 4.46 (s, 2H), 7.1 s 7.4 (m, 7H) IR (NaCl plate, cm-1): 3350 (NH)

Example 2

Production of 1- (4,6-dimethoxypyrimidin-2-yl) -2-propanone

[0035] In a reactor, 16.0 g (0.4 mol) of 60% sodium hydride, 400 ml of THF and 43.6 g (0.02 mol) of 4,6-dimethoxy-2- were placed methanesulfonylpyrimidine. The reactor contents were heated to 30 ° C. Thereto then 39.4 g (0.68 mol) of acetone was added dropwise, followed by reaction for 2 hours. After the reaction was finished, 350 ml of water was added and extraction was carried out with 500 ml of

15 ethyl acetate. The ethyl acetate layer was concentrated. The concentrate was subjected to distillation under reduced pressure to obtain 8.8 g (44.9 mmol) of 1- (4,6-dimethoxypyrimidin-2-yl) -2-propanone. Refractive index n20 D: 1.5181 MS m / e: 196 (M +) 1H-NMR (CDCl3 / TMS), δ (ppm):

20 2.03 (s), 2.26 (s), 3.86 (s), 3.91 (s, 6H), 5.40 (s), 5.73 (s), 5.91 (s) , 1H) Example 3 Production of 3- (4,6-dimethoxypyrimidin-2-yl) -2-methyl-7-ethylindole [0036] In a reactor 2.4 g (12.2 mmol) of 1- ( 4,6-dimethoxypyrimidin-2-yl) -2-propanone, 1.7 g (9.98 mmol) of 2 hydrochloride

Ethylphenylhydrazine, 1.4 g (10.2 mmol) of zinc chloride and 10 ml of toluene, followed by refluxing for 2 hours with heating. After the reaction was over, the reaction mixture was cooled to room temperature. Water and ethyl acetate were added thereto and phase separation was performed. The ethyl acetate layer was concentrated. The concentrate was subjected to silica gel column chromatographic separation.

30 (developing solvent: n-hexane / ethyl acetate) to obtain 2.38 g (8.01

-11 mmol) of 3- (4,6-dimethoxypyrimidin-2-yl) -2-methyl-7-ethylindole. Yield: 80.3%, Melting point: 90.3 to 94.8º C. MS m / e: 297 (M +) 1H-NMR (CDCl3 / TMS), δ (ppm):

5 1.38 (t, 3H), 2.87 (q, 2H), 2.96 (s, 3H), 4.08 (s, 6H), 5.85 (s, 1H), 7.03 ( d, 1H), 7.18 (t, 1H), 8.18 (bs, 1H), 8.57 (d, 1H)

Example 4 Production of 3- (4,6-dimethoxypyrimidin-2-yl) -2-methyl-7-methoxymethylindole [0037] 6.2 g (31.6 mmol) of 1- (4.6 were introduced into a reactor)

10 dimethoxypyrimidin-2-yl) -2-propanone, 4.8 g (31.5 mmol) of 2-methoxymethylphenylhydrazine, 4.76 g (34.9 mmol) of zinc chloride and 60 ml of toluene. Reflux was carried out for 2 hours with heating. After the reaction was over, the reaction mixture was cooled to room temperature. Water and ethyl acetate were added and phase separation was performed. The ethyl acetate layer is

15 concentrated. The resulting crystals were washed with diisopropyl ether to obtain 4.57 g (14.6 mmol) of 3- (4,6-dimethoxypyrimidin-2-yl) -2-methyl-7-methoxymethylindole. Yield: 46%. MS m / e: 313 (M +) 1H-NMR (CDCl3 / TMS), δ (ppm): 2.95 (s, 3H), 3.34 (s, 3H), 4.06 (s, 6H), 4.74 (s, 2H), 5.81 (s, 1H), 7.0 to 7.1 (m, 3H), 8.65 (d, 1H)

Example 5 Production of 3- (4,6-dimethoxypyrimidin-2-yl) -2-methylindole [0038] In 10 ml of toluene 1.61 g (8.2 mmol) of 1- (4,6-dimethoxypyrimidine) were dissolved 2-yl) -2-propanone and 1.08 g (10 mmol) of phenylhydrazine. To this solution were added 1.36 g (10 mmol) of zinc chloride, followed by reflux

25 for 1 hour. The reaction mixture was allowed to cool and ethyl acetate and water were added to dissolve the entire reaction mixture. The oil layer was washed with water, separated and dried over Glauber's salt. The resulting oil layer was concentrated under reduced pressure to obtain an orange solid. The solid was recrystallized from methanol to obtain 1.37 g (5.1 mmol) of 3- (4,6-dimethoxypyrimidin-2-yl) -2

30 methylindole Yield: 62%, melting point: 182 to 184 ° C. MS m / e: 269 (M +).

-121H-NMR (CDCl3 / TMS), δ (ppm): 2.94 (s, 3H), 4.06 (s, 6H), 5.81 (s, 1H), 7.1 (m, 2H) , 7.3 (m, 1H), 8.7 (m, 1H) IR (KBr, cm-1): 3490 (NH), 1570

Example 6

Production of 3- (4,6-dimethoxypyrimidin-2-yl) -2,7-dimethylindole

[0039] In 20 ml of toluene 0.77 g (3.9 mmol) of 1- (4,6-dimethoxypyrimidin-2-yl) -2-propanone and 0.69 g (4.3 mmol) of hydrochloride were dissolved of 2-methylphenylhydrazine. To this solution was added 0.64 g (4.7 mmol) of zinc chloride, followed by reflux for 1 hour. The reaction mixture was allowed to cool and ethyl acetate and water were added to dissolve the entire reaction mixture. The layer

The oil was washed with water, separated and dried over Glauber's salt. The resulting oily layer was concentrated under reduced pressure using a rotary evaporator, to obtain an orange solid. The solid was treated with ethyl acetate / n-hexane to obtain 0.38 g (1.34 mmol) of 3- (4,6-dimethoxypyrimidin-2-yl) -2,7 dimethylindole. Yield: 34%, Melting point: 145 to 147 ° C, MS m / e: 283 (M +).

1H-NMR (CDCl3 / TMS), δ (ppm): 2.47 (s, 3H), 2.90 (s, 3H), 4.05 (s, 6H), 5.83 (s, 1H) , 6.98 (d, 1H), 7.13 (t, 1H), 8.15 (d, 1H), 8.50 (d, 1H) IR (cm-1): 3350 (NH) Example 7 Production 5-Chloro-3- (4,6-dimethoxypyrimidin-2-yl) -2-methylindole [0040] To 80 ml of toluene, 8.0 (40 mmol) of 1- (4.6

20 dimethoxypyrimidin-2-yl) -2-propanone and 7.9 g (44 mmol) of 4-chlorophenylhydrazine hydrochloride. To this was then added 6.54 g (48 mmol) of zinc chloride. Reflux was performed for 2 hours with heating. The reaction mixture was allowed to cool. Ethyl acetate and water were then added to dissolve the entire reaction mixture. The organic layer was washed with water, separated and dried over salt.

25 of Glauber. The resulting organic layer was concentrated under reduced pressure using a rotary evaporator to obtain an orange solid. The solid was washed with isopropylether to obtain 10.2 g (33.7 mmol) of 5-chloro-3- (4,6-dimethoxypyrimidin-2-yl) -2-methylindole. Yield: 84%, Melting point: 179 to 181 ° C, MS m / e: 303 (M +). 1H-NMR (CDCl3 / TMS), δ (ppm):

30 2.91 (s, 3H), 4.04 (s, 6H), 5.82 (s, 1H), 7.1 (m, 1H), 7.3 (m, 1H), 8.7 ( m, 1H)

-13IR (KBr, cm-1): 3510 (NH), 1580

Example 8 Production of 3- (4,6-dimethoxypyrimidin-2-yl) -5-methoxy-2-methylindole [0041] To 80 ml of toluene, 8.0 g (40 mmol) of 1- (4.6

5-dimethoxypyrimidin-2-yl) -2-propanone and 7.7 g (44 mmol) of 4-methoxyphenylhydrazine hydrochloride. To this was added 6.0 g (44 mmol) of zinc chloride. Reflux was performed for 2 hours with heating. The reaction mixture was allowed to cool. Ethyl acetate and water were then added to dissolve the entire reaction mixture. The oil layer was washed with water, separated and dried over Glauber's salt.

The resulting organic layer was concentrated under reduced pressure using a rotary evaporator to obtain, as an orange solid, 8.0 g (26.7 mmol) of 3- (4,6-dimethoxypyrimidin-2-yl) -5 -methoxy-2-methylindole. Yield: 67%. Recrystallization was carried out in toluene. Melting point: 182 to 184º C

15 MS m / e: 299 (M +). 1H-NMR (CDCl3 / TMS), δ (ppm): 2.87 (s, 3H), 3.89 (s, 3H), 4.07 (s, 6H), 5.84 (s, 1H), 6.9 (m, 1H), 7.2 (m, 1H), 8.2 (b, 1H), 8.7 (s, 1H) IR (cm-1): 3340 (NH), 1570

Industrial application [0042] In accordance with the present invention a process is provided

20 for the production of a substituted indole compound that constitutes an important intermediate compound for a sulfonanilide compound that exhibits an excellent herbicidal effect.

Claims (1)

1. -Procedure for the production of a substituted indole compound represented by the following general formula (3): image 1 5 (in the formula, R1, R2 and R3 are each independently an alkyl group, an alkoxy group, an alkoxyalkyl group, a haloalkyl group, a carboxyl group, an alkoxycarbonyl group, an alkylcarboxamido group, a nitro group, an aryl group , an arylalkyl group, an aryloxy group, a halogen atom or a hydrogen atom; and X and Y are each independently a hydrogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a haloalkyl group, a carboxyl group, an alkoxycarbonyl group or a halogen atom), characterized in that it comprises reacting, in the presence of an acid, a compound of (pyrimidin-2-yl) -2-propanone represented by the following general formula (1): image 1 (in the formula, R1, R2 and R3 are defined as above), with a hydrazine compound represented by the following general formula (2): image 1 (in the formula, X and Y are defined as above).