Verfahren zur Herstellung neuer heterocyclischer Verbindungen

摘要

Novel compounds of the Formula I wherein n is zero or one., R1 is hydrogen or an alkyl group of 1 to 6 carbon atoms; R2 is an alkyl group of 1 to 6 carbon atoms or a phenyl group but is not methyl when R1 is hydrogen; R3 is hydrogen, an alkyl, alkenyl, alkynyl or alkanoyl group of 1 to 6 carbon atoms or a phenylalkyl group, the alkyl group having 1 to 6 carbon atoms, or a benzoyl group, and R4 and R5 taken together with the carbon atom to which they are attached form a saturated 5 to 7 membered hydrocarbon ring are prepared by reacting a cyclic ketone R4COR5 with an a -halonitrile of Formula IV and either hydrogenating the resulting hydroxylated nitrile of Formula V to produce the hydroxylated amine and completing the cyclization by treating the amine with a carbonyl derivative to produce the compound of Formula I in which R3 is hydrogen, or hydrolysing the hydroxylated nitrile of Formula V to the amide and completing the cyclization with a suitable agent, e.g. aqueous alkali metal hypobromite to give a compound of Formula I in which n is zero and R3 is hydrogen. In either case, alkylation, phenylalkylation or acylation of the products give a compound of Formula I in which R3 is one of the groups other than hydrogen. Preferred carboxyl derivatives for the cyclization of the amine include carbonic acid diesters, urea or urethane in the presence of an alkali metal alkoxide, or phosgene in the presence of a base. Pharmaceutical compositions for the treatment of cardiac conditions, especially in protection against ventricular fibrillation comprise compounds of Formula I with a suitable carrier and can be administered in the form of aqueous solutions or suspensions by means of intraperitoneal or intraduodenal injections.