▎ 摘　　要

NOVELTY - Preparing sildenafil free base (I) or their salts by integrated continuous flow process comprises (a) treating aryl aldehyde (II) with 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide (III) in presence of solid acid catalyst to obtain substituted 1-methyl-5-phenyl-3-propyl-1H,6H,7H-pyrazolo(4,3-d)pyrimidin-7-one (V), (b) continuous flow reaction of (V) in presence of chlorosulfuric acid to get substituted 1-methyl-3-propyl-5-(3-sulfonylphenyl)-1H,6H,7H-pyrazolo(4,3-d)pyrimidin-7-one (VII), (c) continuous flow conversion of (VII) in the presence of compound 8 (e.g. methylpiperazine, 1-ethylpiperazine and 1-phenylpiperazine) to obtain (I), and (d) integrated continuous flow conversion of (II) in the presence of a solvent to provide (I). USE - The method is useful for preparing (I), which is used to treat sexual dysfunction, or erectile dysfunction. No biological data given. ADVANTAGE - The process: produces (I) without intermediate purification and solvent exchange synthesis process; has faster heating, better mass transfer, micro-mixing, optimal radiation penetration, higher reproducibility, improved safety profile, minimal waste generation; is environmentally friendly, efficient, improved, simple, economical and scalable; is automated PDE-5 inhibitors synthesis in 32.4 minutes with improved overall yield; and is quick. DETAILED DESCRIPTION - Preparing sildenafil free base (I) or their salts by integrated continuous flow process comprises (a) treating substituted aryl aldehyde compound of formula (II) with amino 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide of formula (III) in presence of solid acid catalyst to obtain substituted 1-methyl-5-phenyl-3-propyl-1H,6H,7H-pyrazolo(4,3-d)pyrimidin-7-one of formula (V), (b) continuous flow reaction of (V) in presence of chlorosulfuric acid to get substituted 1-methyl-3-propyl-5-(3-sulfonylphenyl)-1H,6H,7H-pyrazolo(4,3-d)pyrimidin-7-one of formula (VII), (c) continuous flow conversion of (VII) in the presence of the compound 8 (e.g. methylpiperazine, 1-ethylpiperazine and 1-phenylpiperazine) to obtain (I), (and) (d) integrated continuous flow conversion of the (II) in the presence of a solvent to provide (I). R1 = O-CH3, H, Fl, Cl, Br, preferably O-ethyl; and R2 = piperazine, methylpiperazine, ethylpiperazine, phenylpiperazine, 2-(piperazin-1-yl)ethan-1-ol, morpholine, 1-benzhydrylpiperazine, ethyl piperazine-1-carboxylate or 1-methyl-1,4-diazepane.