SU440836A1 - METHOD OF OBTAINING 2- {FURILMETHIL) - 6,7-BENZOMORPHANES - Google Patents

Description

one

A method is proposed for the preparation of new derivatives of 6,7-benzomorphans, namely 2- (furylmethyl) -6,7-benzomorphans with high physiological activity.

The proposed method is based on the known reaction of alkylation of amines with quaternary ammonium salts. By applying the known reaction to 6,7-benzomorphans and a quaternary salt, one of the components of which is the furylmethyl radical, the authors obtained new derivatives of 6,7-benzomorphaps, which possess valuable properties.

The method of obtaining 2- (furylmethyl) -6,7-benzomorfanov General formula I

R2 is a hydrogen atom, a methyl or ethyl group;

Rs represents a hydrogen atom, a methyl or ethyl group, or a salt thereof, in that the benzomorphane of formula 2

ten

15

Bt

where RI and R2 are as defined;

R4 means a hydrogen atom, an alkyl, aralkyl or acyl group,

subjected to interaction with the Quaternary ammonium salt of the formula 3

(H, .C D-CH24T-2

25 led by chemical reaction into a hydrogen atom or a methyl or ethyl group; And the anion of an inorganic or organic acid, followed by isolation of the target product in free form or in the form of its salt by known methods. To obtain a compound of formula 1, in which R represents a hydrogen atom, the alkyl or acyl groups in the resulting compounds are removed by saponification of the latter, and to obtain the target compounds of formula 1, where R is a methyl or acetyl radical, the resulting compounds of formula 1, where R This means that hydrogen is methylated or acetylated. The reaction is preferably carried out in an inert solvent, for example dimethylformamide, at an elevated temperature, preferably at 100-200 ° C. The quaternary ammonium salt (or used, if necessary, a quaternary base) is added in a calculated amount or in excess, preferably up to 3 mol by 1 mol of benzomorphane of formula 2. The reaction mixture is worked up, and the reaction product is isolated and purified by conventional techniques. Example. Methanesulfate 2- (furfuryl) 2-hydroxy-5, 9a-dimethyl-6,7-benzomorfana. 2.17 g (0.01 mol) of 2-hydroxy-5,9a-dimethyl-6, 7-bispsomorphia in 5 ml of dimethylformamide with 8.0 g (0.03 mol) of furfuryltrimethylammonium iodide are heated and an oil bath to 150 ° With stirring for 1.5 hours. The dimethylformamide is then distilled off in vacuo and the residue is shaken with 50 ml of chloroform and 25 ml of 2N. ammonia. The chloroform extract is separated, washed with water, dried over sodium sulfate, and evaporated in vacuo. The residue is dissolved in approximately 10 ml of absolute ethanol and, after acidification with methanesulfonic acid, absolute ether is added to the solution until cloudiness begins. The meta-sulfonate crystallizes out, which is left to stand in the refrigerator overnight for complete crystallization, then it is sucked off and washed first with ethanol / ether (1: 1) and then with ether, then dried at 80 ° C, yield 1.5 g (39% of theoretical), so pl. 158-162 ° C, after recrystallization from ethanol / ether t. Pl. 163-165 ° C. The following compounds can be prepared in a similar way: 2-furfuryl-2-hydroxy-a-5-methyl-9-ethyl-6.7 benzomorphane, m.p. 156 ° C (methanesulfonate); 2-furfuryl - 2-hydroxy - a - 5-ethyl-9-methyl-b, 7-benzomorphan, t. Pl. 254 ° C (salt with HC1); 2-furfuryl - 2-hydroxy - a-5,9-diethyl-6,7-benzomorfan, t. Pl. 236 ° C (salt with HC1); 2- (3-methylfurfuryl) -2-hydroxy-a-5,9-dimethyl-6, 7-benzomorphan, t. Pl. 119 ° C; 2- (3 - methylfurfuryl) -2-hydroxy-a-5,9-diethyl6, 7-benzomorphan, t. Pl. 201 ° C; 2- (3-methylfurfuryl) -2-hydroxy-a-5-methyl-9-ethyl-6, 7-benzomorfan, t. Pl. 177 ° C; 2- (3-methylfurfuryl) -2-hydroxy-a-5-ethyl-9methyl-6, 7-benzomorphan, t. Pl. 178 ° C; 2- (5-methylfurfuryl) -2-hydroxy-a-5,9-dimethyl-6, 7-benzomorphan, t. Pl. 232 ° C (salt with HC1); 2- (5-methylfurfuryl) -2-hydroxy-a-5-methyl9-ethyl-6, 7-benzomorphan, t. Pl. 169 ° C; 2- (5-methylfurfuryl) -2 - hydroxy - a - 5 - ethyl9-methyl-6, 7-benzomorphan, t. Pl. 140 ° C (salt with HC1); 2- (5-methylfurfuryl) -2 - hydroxy - a - 5.9 - diethyl-6, 7-beisomorphane, t. Pl. 147 ° C; 2-furylmethyl - (3) - 2 - hydroxy-a-5,9-dimethyl-6, 7-benzomorpha, t. Pl. 252 ° C (salt with HC1); 2-furylmethyl - (3) -2 - hydroxy-a-5-methyl-9-ethyl-6, 7-benzomorphan, t. Pl. 268 ° C; - methylfurylmethyl- (3) - 2-hydroxy-a-5,9 dimethyl-6, 7-benzomorfan, t. pl. 250 ° C (salt with HC1); 2-furfuryl-2 - acetoxy-a-5,9 - dimethyl-6, 7-benzomorfan, t. Pl. 135 ° C (salt with HC1); 2-FURFURIL-2 - methoxy-a-5,9 - dimethyl-6,7 benzomorphan, t. Pl. 210 ° C (salt with HC1); 2- 2-methylfurfurylmethyl - (3) -2 - acetoxy-a-5, 9-dimethyl - 6.7 - benzomorphane, melting point 215 ° C (HC1 salt); - methylfurylmethyl - (3) -2-methoxy-a5, 9-dimethyl - 6,7 - benzomorphan, t. pl. 128 ° C (salt with HC1); 2-furfuryl - 2 - hydroxy - 6,7 - benzomorphan, t. Nl. 192 ° C (s); 2- furylmethyl - (3) -2-hydroxy - 6,7 - benzomorfan, t. Pl. 240 ° C (salt with HC1); 2- 2-methylfurylmethyl - (3) -2 - hydroxy-6,7 benzomorphan, t. Nl. 223 ° C (salt with HC1); 2- (3 - metnlfurfuril) -2-6.7 - benzomorfan, t. Pl. 236 ° C (salt with HC1); 2-furfuryl - 2 - hydroxy-5 - methyl - 6.7 - benzomorpha, t. Pl. 188 ° C; 2-furfuryl - 2 - OXI-5-ETHIL-6,7-benzomorfan, t. Pl. 242 ° C (salt with HC1); 2-furfuryl - 2 - hydroxy - 5-isopropyl-6,7-benzomorfan, t. Pl. 176 ° C; 2-furfuryl - 2 - hydroxy-5-n-propyl-6,7-benzomorfan, t. Pl. 174 ° C; 2-FURFURIL-2 - hydroxy-5-n-butyl-6,7-benzomorfan, t. Pl. 160 ° C; 2-furylmethyl- (3) -2-hydroxy-5-methyl-6.7 benzomorphan, t. Pl. 179 ° C; 2-furylmethyl- (3) -2-hydroxy-5-ethyl-6.7 benzomorphane, m.p. 225 ° C (salt with HC1); 2-furylmethyl- (3) -2-hydroxy-5-n-propyl-6, 7-benzomorphan, t. Pl. 182 ° C; 2-furylmethyl- (3) -2 - hydroxy - a-5-ethyl-9methyl-6, 7-benzomorphan, t. Pl. 268 ° C (salt with HC1); 2-furylmethyl- (3) -2 - hydroxy - a-5,9-diethyl 6, 7-benzomorfan, t. Pl. 278 ° C (salt with HC1); 2- (5-ethylfurfuryl) -2 - hydroxy-a - 5.9 - dimethyl-6, 7-benzomorphan, t. Pl. 151 ° C;