Azamorphinan and related compounds. I. A synthesis of 2-hydroxy-N-methyl-9-azamorphinan (studies on the syntheses of heterocyclic compounds. CCXIV.

Abstract

In order to examine the analgesic action of azamorphinan attempt to synthesize 3-hydroxy-N-methyl-9-azamorphinan (III) which has an additional nitrogen in morphinan ring was carried out successfully. Hydrolysis of 2-ethoxycarbonylmethyl-2-(3-methoxyphenyl) cyclohexanone (IX), which was obtained by condensation of 2-(3-methoxyphenyl) cyclohexanone (VIII) with ethyl bromoacetate in the presence of sodium amide, was first examined to give 2-carboxymethyl-2-(3-methoxyphenyl) cyclohexanone (X), whose methylhydrazination with methyl hydrazine afforded 3, 4, 5, 6, 7, 8-hexahydro-2H, 4aH-4a-(3-methoxyphenyl)-2-methyl-3-oxocinnoline (XI). Secondly, reduction of the preceding compound (XI) with lithium aluminum hydride gave 4a-(3-methoxyphenyl)-2-methyldecahydrocinnoline (XII), which was converted into 3-methoxy-N-methyl-9-azamorphinan (XV) by Pictet-Spengler reaction with formalin and hydrochloric acid. Finally, demethylation of XV with hydrobromic acid afforded 3-hydroxy-9-azamorphinan (III), which was characterized as the picrate of its benzoate (XVI). Furthermore, conformation of XV was discussed.