Facile and Cost-Effective Route for the Synthesis of Simmerafil

Abstract

An improved synthesis of simmerafil, a potent PDE5 inhibitor as a clinical candidate, is described with a 38.1% overall yield and 99.7% purity. Starting from the safe and inexpensive salicylamide (15), the key intermediate 2-propoxybenzimidamide (21), which is also a potential precursor for the preparation of pyrimidinone derivatives, was effectively and conveniently obtained. The subsequent process from 21 to simmerafil was optimized, which makes it more amenable to scale-up.

An Alternative Approach to Synthesize Sildenafil via Improved Copper-Catalyzed Cyclization

“…In our previous work, we reported on the synthesis of 2-propoxybenzamide. 24 Herein, we successfully applied this strategy for the synthesis of 2-ethoxybenzamidine. We started with commercially available 2-ethoxybenzamide and obtained the corresponding benzamidine moiety 21 via imidoesterification and subsequent ammonolysis, achieving an overall yield of 81.6% and 99.2% purity.…”

“…Subsequently, to establish the necessary precursors, we started to synthesize two strategic elements, 21 (Scheme A) and 15 (Scheme B), for the synthesis of sildenafil. In our previous work, we reported on the synthesis of 2-propoxybenzamide . Herein, we successfully applied this strategy for the synthesis of 2-ethoxybenzamidine.…”