反应详情

温度

180 °C

To a solution of N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide (110 mg, 0.23 mmol) (see Example 48, step F) in anhydrous i-PrOH (3 mL) was added 2-methyl-1,2,3,4-tetrahydroisoquinolin-7-amine (39 mg, 0.24 mmol), followed by catalytic 12M HCl. After heating for 10 min in the microwave at 180° C., the reaction was quenched with saturated NaHCO3 (25 mL), the solvent removed by rotary evaporation, and the aqueous layer extracted with DCM (25 mL). The organic layer was concentrated and purified by column chromatography (1-10% MeOH in DCM) to provide the product (74 mg, 53%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 2.28 (s, 3H), 2.53-2.55 (m, 2H), 2.70-2.72 (m, 2H), 3.36 (s, 2H), 3.87 (s, 3H), 3.97 (s, 2H), 6.49 (d, 1H, J=5.1 Hz), 6.94-6.95 (m, 2H), 7.05-7.13 (m, 2H), 7.25-7.27 (d, 1H, J=8.1 Hz), 7.35-7.43 (m, 3H), 7.48 (s, 1H), 8.19 (d, 1H, J=5.3 Hz), 8.31 (s, 1H), 8.43 (d, 1H, J=8.6 Hz), 8.78 (d, 1H, J=6.8 Hz) 9.38 (s, 1H), 9.45 (s, 1H) ppm. ES-LC/MS m/z=602 [M+H]+.

1. customthe reaction was quenched with saturated NaHCO3 (25 mL)
2. customthe solvent removed by rotary evaporation
3. extractionthe aqueous layer extracted with DCM (25 mL)
4. concentrationThe organic layer was concentrated
5. custompurified by column chromatography (1-10% MeOH in DCM)