Synthesis of 4-Aza-3-oxo-androstane-17β-carboxylic Acid, a Key Intermediate for the Preparation of Potent 5α-Reductase Inhibitors

A key intermediate, 4-aza-3-oxo-androstane-17β-carboxylic acid, for the preparation of some potent 5α-reductase inhibitors was synthesized in 5 steps from the known methyl 3-oxo-4-androstene-17β carboxylate. The construction of 4-aza-3-oxo-ring A of the steroid was achieved conveniently by a novel one-step simultaneous lactam formation and N-debenzylation of methyl 3-(2,4-dimethoxylbenzylamine)-5-oxo- A-nor-3,4-seco-androstane-17β -carboxylate with 4 equivalents of p-TsOH.