method of preparation of 10 (piperazino) - 10,11-dihydrodibenzo (b, f) - thiepines with a substituent at c-4 of the nucleus piperazinique and salts thereof, and products obtained

摘要

1313428 Piperazino-dibenzothiepin derivatives SPOFA UNITED PHARMACEUTICAL WORKS 28 May 1971 [28 May 1969] 25681/70 Heading C2C Dibenzothiepin derivatives (some of which are novel) of the Formula I wherein RSP1/SP is a hydrogen or halogen atom, an alkyl group R, a trifluoromethyl group, an alkoxyl group OR, an alkylthio group SR, an alkanesulfonyl group SO 2 R, or a nitro or cyano group, and RSP2/SP is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aralkyl, hydroxyalkyl, acyloxyalkyl, dialkylaminoalkyl or alkoxycarbonylalkyl group, the alkyl groups represented by R having a straight or branched chain and having from 1 to 4 carbon atoms, the cycloalkyl groups being cyclopropyl to cyclooctyl groups, the acyl group being derived from an aliphatic carboxylic acid with from 2 to 5 carbon atoms and the aralkyl group optionally being substituted in the benzene ring with an alkyl group, a halogen atom, an alkoxyl group, an alkylthio group or a trifluoromethyl group, with the proviso that when RSP2/SP is a 4-methoxybenzyl group, RSP1/SP is hydrogen atom or a trifluoromethyl group, an alkanesulphonyl group, a nitro group or a cyano group only, and acid addition salts thereof, are prepared by reacting a secondary amine of the Formula II with a reactive ester of an alcohol of the formula RSP2/SP-OH, and optionally reacting the product with an acid to form the corresponding acid addition salt. The novel compounds are those in which RSP1/SP and RSP2/SP have the meanings given above with the following provisos: (i) when RSP2/SP is a 4-methoxybenzyl group, RSP1/SP is not a halogen atom, an alkyl group R, an alkoxy group OR, nor an alkylthio group SR; (ii) when RSP2/SP is an alkylcarbonyloxyalkyl group, RSP1/SP is not a halogen atom; (iii) when RSP2/SP is methyl, RSP1/SP shall not be a halogen atom, an alkyl group R, a trifluoromethyl group, an alkoxyl group, an alkanesulphonyl group, alkylthio or a nitro group; (iv) when RSP2/SP is an alkyl or hydroxyalkyl group, RSP1/SP shall not be a halogen atom or a cyano group; and the addition salts of such substituted thiepins. Compounds of the Formula II are prepared by reacting piperazine or 1-(ethoxycarbonyl)- piperazine with an 8-RSP1/SP-10-chloro-10,11-dihydrodibenzo(b,f)thiepin and, when 1-(-ethoxycarbonyl)piperazine is used, hydrolysing the resulting ester. Pharmaceutical compositions having pharmacodynamic, sedative, hypothermic, antiserotonin, antihistaminic, vasodilatory, and cataleptic activity, comprise a novel compound I together with a pharmaceutical carrier.