▎ 摘　　要

NOVELTY - Preparing sildenafil free base (I) or compound of it by using integrated continuous flow process comprises: (a) treating aryl aldehyde derivatives (II) with amino derivatives (III) in presence of solid acid catalyst (IV) to obtain cyclized 1-methyl-5-phenyl-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-7(6H)-one derivatives (V); (b) continuous flow reaction of (V) in presence of chlorosulfuric acid (VI) to get 5-(3-hydrosulfonylphenyl)-1-methyl-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-7(6H)-one derivatives (VII); (c) continuous flow conversion of (VII) in the presence of the ether compound (VIII) to obtain (I); and (d) integrated continuous flow conversion of (II) in the presence of a solvent to provide the final (I). USE - The process is useful for preparing sildenafil free base (I) to treat erectile dysfunction. No biological data given. ADVANTAGE - The process: develops integrated continuous flow multi-operational protocol for the synthesis phosphodiesterase-5 inhibitors; provides automated phosphodiesterase-5 inhibitors synthesis in 32.4 minutes time with improved overall yield (in general phosphodiesterase-5 synthesis need 10-30 days' time through routine synthetic protocols (batch process); utilizes developed an advance integrated continuous flow multi-operational protocol platform involving catalysis, separation, without intermediate purification and solvent exchange chemistry; and provides additional plug and play research ultimately enable the integrated continuous synthesis of modern small molecule pharmaceuticals, including enantiopure active pharmaceutical ingredients to fill future gap for quick manufacturing of the late stage functionalized biological active compounds. DETAILED DESCRIPTION - Preparing sildenafil free base of formula (I) or compound of it by using integrated continuous flow process comprises: (a) treating aryl aldehyde derivatives of formula (II) with amino derivatives of formula (III) in presence of solid acid catalyst (IV) to obtain cyclized 1-methyl-5-phenyl-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-7(6H)-one derivatives of formula (V); (b) continuous flow reaction of (V) in presence of chlorosulfuric acid (VI) to get 5-(3-hydrosulfonylphenyl)-1-methyl-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-7(6H)-one derivatives of formula (VII); (c) continuous flow conversion of (VII) in the presence of the ether compound (VIII) to obtain (I); and (d) integrated continuous flow conversion of (II) in the presence of a solvent to provide the final (I). R1 = OCH3, OC2H5, H, Fl, Cl or Br; 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.