Synthesis of diversely substituted 5-methylpyrazolo[1,5-a]pyrimidines assisted by ultrasound in aqueous media: Molecular docking for potential antiviral, anticancer activities

Abstract

5-Methylpyrazolo[1,5-a]pyrimidine derivatives have been synthesized with starting materials that are eithercommercially or easily available. This is achieved by the ultrasonication of 3-amino-1H-pyrazoles (3-7) and enaminones (2) assisted by KHSO4 in aqueous medium. The structures are established by spectral and analytical techniques. An X-ray crystallographic study of compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-7-(4-methoxyphenyl)- 5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide (8b) confirms the structural orientation and eliminates any ambiguitypertaining to its regioselectivity. Its space group is P21/n with the following unit cell parameters: a = 17.5775 (8),b = 7.1707 (4), c = 18.113 (1) Å, β = 91.449 (2) and Z = 4. Crystal structure is solved to a final R value of 0.062 and to aGOOF value of 1.09. Molecular docking of the compounds has been executed to identify the potential antiviral andanticancer agents. Moreover, molecular dynamics simulation study of the ligand 9c in a complex with 3pp0, reveals thestability of the potential ligand candidate 9c.