Enaminonitrile derivative, 6-amino-4-(2-chloro-5-nitrophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1) was synthesized. This compound was utilized as a building block for the synthesis of new 3-methylpyrazolopyran moiety incorporated with different heterocycles involving pyrimidinone, oxazinone, and iminopyrimidine, in addition to novel derivatives including diacetyl derivative (5), benzoyl derivative (6), carbamodithioic acid (10) and urea derivative (13). Spectral techniques, FT-IR, 1H-NMR and mass spectroscopy and elemental analysis were used to characterize the synthesized compounds. Screening and evaluation of these products as antimicrobial agents showed that the derivatives 5, 6, 10, and 13 possess a potent activity.