Piperidine → Henatinib

Participants

Reaction Steps

(R,Z)-2-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 53f (50 mg, 0.149 mmol) was dissolved in 261 μl of ethanol under stirring, and added with 5-fluoro-1,3-dihydro-indol-2-one (20.28 mg, 0.134 mmol) and piperidine (7.3 μl, 0.074 mmol) to the solution at room temperature. Upon completion of the addition, the reaction mixture was stirred for 2 hours in dark at 80° C. in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the oil bath was removed, and the reaction mixture was naturally cooled down to room temperature, filtered and dried to obtain the title compound (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 53 (40 g, yield 57%) as a yellow solid.

Provenance & Evidence