Synthesis of Estimated Metabolites of 9-Amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline Monohydrochloride Monohydrate (NIK-247). I. Synthesis of Mono-hydroxylated Metabolites

Abstract

The two mono-hydroxylated metabolites of 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate (NIK-247), which is a new drug for the treatment of dementia, were synthesized to determine their chemical structures. Reduction of two tricyclic ketones, 9-amino-1, 2, 3, 5, 6, 7-hexahydro-8H-cyclopenta [b] quinolin-8-one and 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b]-quinolin-1-one, with NaBH₄ afforded the corresponding racemic alcohols. The optically active mono-hydroxylated metabolites, (+)-9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinolin-8-ol and (+)-9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinolin-1-ol, were obtained by optical resolution of each racemic alcohol using (+)-di-p-toluoyl-D-tartaric acid.