PROCEDIMIENTO PARA LA PRODUCCION DE DERIVADOS DE FENOTIACI-NA.

摘要

1,178,623. Phenothiazines. SANDOZ Ltd. 10 April, 1967 [10 May, 1966; 16 May, 1966; 8 Sept., 1966 (2); 8 March, 1967 (3)], No. 16325/67. Heading C2C. Compounds of the formula and their acid addition salts, in which R 1 is H, halogen, acyl (2-5 C), alkoxy or alkylthio (1-4 C), CF 3 or CN; R 2 is H or Me and either each of R 3 and R 4 is alkyl (1-4 C) or R 3 and R 4 together with the N-atom is a pyrrolidine, piperidine morpholine or N-methylpiperazine and R 5 is H or R 3 is alkyl (1-4 C) and R 4 together with R 5 is -CH 2 -CH 2 - are prepared (a) by reacting a compound of the formula wherein X is Cl, Br or I, or the residue of an organic sulphonic acid with a compound of the formula in an organic solvent and in the presence of an acid binding agent at 100-200‹ C., (b) by condensing a compound of the formula with a compound of the formula where X1 is Cl, Br or I in an inert solvent and in the presence of an alkali metal amide, (c) by condensing a compound of the formula where R 6 is alkyl (1-3 C) with a compound of Formula III at 150-200‹ C., (d) by reacting a compound of the general formula with a compound of the formula in an inert organic solvent and in the presence of an acid binding agent and decarboxylating by heating the resulting ester and (e) to give compounds (I) where R is H, halogen, alkoxy or alkylthio only, by reacting a compound of the formula where R1 1 is H, halogen, alkoxy or alkylthio (1-4 C) with a compound of the formula in an inert solvent and in the presence of an alkali metal amide and hydrolysing the resulting complex. 1 - (3 - Chloropropyl) - 4 - hydroxy - 4 - (I - methyl - 2 - oxo - 3 - pyrrolidinyl) - piperidine is prepared from 4-hydroxy-4-(1-methyl-2-oxo-3- pyrrolidinyl) - piperidine and 1 - bromo - 3 - chloropropane; 2 - chloro - 10 - (3 - ethoxycarbonyloxypropyl)-phenothiazine from the corresponding alcohol and Cl.COOEt; 1-(3-hydroxy propyl) - 4 - hydroxy - 4 - (1 - methyl - 2 - oxo - 3 - pyrrolidinyl) - piperidine from 4 - hydroxy - 4 - (1 - methyl - 2 - oxo - 3 - pyrrolidinyl) - piperidine and 1-bromo-3-propanol and 1-(3-chloropropyl) - 4 - (dimethylcarbamoylmethyl)- 4 - hydroxy-piperidine from 4-(dimethylcarbamoylmethyl)-4-hydroxy-piperidine and 1-bromo-3- chloropropane. Pharmaceutical compositions useful as tranquillizers and antihypertensive agents comprise compounds of Formula (I) and a carrier therefore. The compositions may be in a form suitable for enteral or parenteral administration.