反应详情

HATU (220 mg) and triethylamine (0.08 mL) were added to a dichloroethane (10 mL) solution of 4-tert-butyl-2-{[(1S,2S)-2-pyrrolidin-1-ylcyclohexyl]amino}benzoic acid (200 mg) and 7-amino-1-methyl-3,4-dihydroquinolin-2(1H)-one (102 mg), followed by stirring at room temperature for 12 hours. A 1 M sodium hydroxide aqueous solution was added to the reaction liquid, followed by extraction with chloroform. After drying of the organic layer, the solution was concentrated under a reduced pressure and the resulting residue was purified by silica gel column chromatography (chloroform:methanol, 95:5). By adding fumaric acid (22 mg) to an ethyl acetate solution of the resulting free base, 4-tert-butyl-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-2-{[(1S,2S)-2-pyrrolidin-1-ylcyclohexyl]amino}benzamide fumarate (190 mg) was obtained as a solid.

1. extractionfollowed by extraction with chloroform
2. customAfter drying of the organic layer
3. concentrationthe solution was concentrated under a reduced pressure
4. customthe resulting residue was purified by silica gel column chromatography (chloroform:methanol, 95:5)
5. additionBy adding fumaric acid (22 mg) to an ethyl acetate solution of the resulting free base