SU1728242A1 - Method of 3-amino-1(2h)-isoquinolones synthesis - Google Patents

Abstract

The invention relates to heterocyclic compounds, in particular, the method of producing 3-amino-1 (2H) isoquinolones of the total fi l U3 O N-RJ nng R with Ps H and R4 N02 1) R1 CeH5CH2, IG F cki; 2) R, JtR2-CH; N 3) Ri - СНз, p, eV-M .4) Ri - Н, R2 2 k JS СБНб, 5) Ri - СБНб, R2 м-СНзО-СеН4, 6) Ri СНз, Ra 3,4- {СНзО ) 2SbNz, 7) RI CH30-m-SbN4, Hi-1 D {, N 4; with Rs CI and R4 H 8) RI m-CH3-CeH4, R2 CN, with Ra R4 L. H, 9) Ri CeHs, Ri SbNb, R2 n-F-CeH5, 3 10) Ri used as analytical reagents. The goal is to increase the yield and expand the range of target products. Synthesis is carried out by reacting a substituted nitrile with amides of o-halobenzoic acids in an organic solvent medium in the presence of a base at 80-153 ° C, followed by removal of the solvent and acidifying the residue to a pH of 7. These conditions increase the yield of the target compounds from 27 to 80%, as well as expand the range of target products. 2 hp f-ly. (l C xj y oo y th

Description

Example 4 Preparation of 3-amino-4- (1-methylbenzimidazol-2-yl) -2-phenyl-1 (2H) isoquinolone.

To a mixture of 1.1 g (0.005 mol) of anilide of fluorobenzoic acid, 0.85 g (0.005 mol) of 1-methyl-2-benzimidazolyl acetonitrile, and 100 ml of dimethylformamide was added 1.0 g (0.01 mol) of tert-butylate sodium and heated at 153P for 1.5 hours. The solvent is evaporated in vacuo, the residue is treated with 80 ml of water, acidified with acetic acid to pH 7, the precipitate is filtered off, washed with water, dried. Yield 1.64 g (90%). M.p. 263 ° C (from acetonitrile).

Calculated,%: C 75.47; H 4.95; N 15.30

C2sHiaN40

Found,%: C 75.21; H 4.45; N 15.29.

PMR spectrum DM CO - de (standard internal TMS): 7.87 ppm (1H); 7.61-7.43 ppm (9H); 7.27-7.03 ppm (G); 6.92 ppm (2H, -MNa); 3.56 ppm (G)

IR spectrum (KBG, tab.): VNH2 3300 v with about 1670 cm 1.

EXAMPLE 5 Preparation of 3-Amino-2-methyl-7-nitro-4- (4-methylthiazol-2-yl) -1 (2H) isoquinolone.

To a mixture of 1.1 g (0.005 mol) of 5-nitro-2-chlorobenzoic acid methylamide, 0.7 g (0.005 mol) of 4-methyl-2-thiazolylacetonitrile and 60 ml of dimethylformamide is added

3.26 g (0.01 mol) of cesium carbonate and heated at 153 ° C for 2 hours. The solvent is evaporated in vacuo, the residue is treated with 90 ml of water, acidified with acetic acid to pH 7, the precipitate is filtered off, washed with water, dried. Output

Claims (3)

1.27g (80%), so pl. 257 ° С (from dioxane). Calculated,%: N 17,71; S 10.13 C14H12N403S Found,%: N 17.83; S 10.20 PMR spectrum in CFaCCteD (internal standard, TMS): 9.23 ppm (1H); 8.36 ppm (1H); 7.93 ppm (1H); 7.11m. 3.87 ppm (ZN, -SNz); 2.81 ppm (ZN, -SNz). IR spectrum (KBG, tab.): VNH2 3395   1645cm 1 PRI me R 6. Preparation of 3-amino-7-nitro-4-phenyl-1 (2H) isoquinolone. To a mixture of 1 g (0.005 mol) of amide-5-nitro-2-chlorobenzoic acid, 0.6 g (0.005 mol) of phenylacetonitrile and 100 ml of acetonitrile, 1.38 g (0.01 mol) of potash was added and heated at 80 ° C for 4 hours. The solvent is evaporated in vacuo, the residue is treated with 100 ml of water, acidified with acetic acid to pH 7, the precipitate is filtered off, washed with water and dried. Yield 1.25 g (90%), so pl. 228 ° С (from nitromethane). Calculated,%: C 64.05; H 3.94; N 14.93 CisHnNsOs Found,%: C 63.78, - H 3.50; N 15.07 PMR spectrum in DMSO - de (internal standard, TMS): 8.76 ppm (1H), 7.87 ppm (1H); 7.57-7.23 ppm (5H); 6.74 ppm (1H); 6.45 ppm (2H, -NH2); 4.43 ppm (1H, -NH-). IR spectrum (KBG, tab.): VNH2 3350-3100 v with about 1660. Example. Preparation of 3-amino-2-phenyl-4- (4-fluorophenyl) -1 (2H) isoquinolone. To a mixture of 1.2 g (0.005 mol) of anilide of o-chlorobenzoic acid, 0.66 g (0.005 mol) of 4-fluorophenylacetonitrile and 80 ml of dimethylformamide were added 3.26 g (0.01 mol) of cesium carbonate and heated at 153 ° C for 3.5 hours. The solvent is evaporated in vacuo, the residue is treated with 120 ml of water, acidified with acetic acid to pH 7, the precipitated precipitate is filtered off, washed with water, and dried. The output of 1.43 g (87%), so pl. 295 ° C (from nitromethane). Calculated,%: N 8.48, F 5.75 C2iHi5N2OF Found,%: N 8.71; F 5.94 PMR spectrum in DMSO - de (standard internal, TMS): 8.06 ppm (1H); 4.62 ppm (2H, -NH2); 7.58-7.12 ppm (11 H); 6.80 ppm (1 N) IR spectrum (KBG, tab.): VNH 2, 3310 cm 1; V 1660cm 1. Example Preparation of 3-amino-4- (3-methoxyphenyl) -7-nitro-2-phenyl-1 (2H) isoquinolone. To a mixture of 2.76 g (0.01 mol) of 5-nitro-2-chlorobenzoic acid anilide, 1.47 g (0.01 mol) of 3-methoxyphenylacetonitrile, and 120 ml of acetonitrile, add 2.76 g (0, 02 mol) of potash and heated at 80 ° C for 4 hours. The solvent is evaporated in vacuo, the residue is triturated with 200 ml of water, acidified with acetic acid to pH 7, the precipitated precipitate is filtered off, washed with water, dried. Yield 3.56 g (92%), m.p. 237 ° С (from nitromethane). Calculated,%: C 68.20; H 4.42; N 10.85 C22H17N304 Found,%: C 67.87; H 4.1; N 10.71. PMR spectrum in DMSO - de (internal standard, TMS): 8.79 ppm (1H); 8.14 ppm (1H); 7.60 ppm (5H); 7.14 ppm (1H); 6.94 (4H); 5.40 ppm (2H, -MNa); 3.80 ppm (ZN, -SNz); IR spectrum (KBG, tab.): VNH2 3320 cm, v with 0 1650 cm 1. PRI me R 9. Obtaining 3-amino-4- (3,4-dimethoxyphenyl) -2-methyl-7-nitro-1 (2H) isoquinolone, To a mixture of 4.3 g (0.02 mol) methylamide 5-nitro-2-chlorobenzoic acid, 3.54 g 2. The way pop. 1, characterized by the fact that in the synthesis of compounds of total RG - Foomula I, where Ri H; SNZ: -CH2SbNy: pioi-2 formula I, where RI N; CH3; -CH2SbN5; piri-Ј Dil-4-I; I P2-4 are as indicated, 5ptj Carbonone-D is used as base. you are alkali metals. R3 H; 3. The method according to claim 1, distinguish them and with R4 H; N02, in the synthesis of compounds in general, tert-buty-formula I, where RI is CeHb-; 3-СНзОСеН4; 10 lats sodium.