反应详情

温度

170 °C

In a sealed high pressure container with a Teflon lining was combined ethyl 1-chloro-4-methoxyisoquinoline-3-carboxylate (EP 650961 A1; 390 mg, 1.55 mmol), 4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidinium trifluoroacetate (Intermediate 86; 1.7 g, 4.4 mmol), and K2CO3 (2.2 g) in 20 ml tert-butanol. The container was heated at 170° C. with stirring for 8 hours. The solution was concentrated by rotary evaporation and reconstituted with EtOAc. The organic layer was washed 4× with H2O, and dried over MgSO4. Crude ethyl 1-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-4-methoxyisoquinoline-3-carboxylate was purified by reverse phase Si yielding 20 mg of the intermediate ester. The ethyl ester was then hydrolyzed as in Example 262 to yield 13.5 mg white solid final product.

1. concentrationThe solution was concentrated by rotary evaporation
2. washThe organic layer was washed 4× with H2O
3. dry with materialdried over MgSO4
4. customCrude ethyl 1-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-4-methoxyisoquinoline-3-carboxylate was purified by reverse phase Si yielding 20 mg of the intermediate ester