Convenient Synthesis and Characterization of Novel 4-[2-Ethoxy-5-(4-Methyl-1-Piperazinesulphonyl)Benzamido]-3-Isobutyl-1-Methyl-1H-Pyrazole-5-Carboxamide: Key Precursor for Isobutyl Sildenafil

Abstract

This work presents a rational synthesis of 4-[2-Ethoxy-5-(4-Methyl-1-Piperazinesulphonyl)benzamido]-3-Isobutyl-1-Methyl-1H-Pyrazole-5-Carboxamide (13) by condensation of 4-amino-3-isobutyl-1-methyl-1H-pyrazole-5-carboxamide (8) with 2-ethoxy-5-(4-methyl-1-piperazinesulphonyl)benzoyl chloride (12) with an overall yield of 37.4 %. The preparative details of all intermediates and Isobutyl Sildenafil were discussed step by step. The structures of key intermediate 13 and Sildenafil impurity A were characterized by 1H NMR, 13C NMR and HR-MS analysis. It provides a convenient approach in good yield for Sildenafil impurity A in a convergent way with easy manipulations and scale up.