Synthesis of new pyrazole and pyrimidine steroidal derivatives

Abstract

The synthesis of steroidal heterocycles containing the pyrazole and pyrimidine ring fused to the 16,17-position of the steroid nucleus is reported. Androstenolone acetate (1) reacted with carbon disulfide, iodomethane and sodium hydride to furnish 3β-acetoxy-16-[bis(methylthio)methylene]-5-androst-5- en-17-one (2). The reactions of 2 with hydrazine hydrate and methylhydrazine afforded the 5'-methylthio-pyrazolo[4',3':16,17]androst-5-en-3β-ols 3a and 3b, respectively. Treatment of 2 with amidinium, guanidinium, and isothiuronium salts in the presence of sodium methoxide yielded the 6'-methoxy-pyrimido[5',4': 16,17]androst-5-en-3β-ols(4a-4e).