反应详情

To a cold (0° C.) solution of N-[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]butane-1,4-diamine (28 mg, 0.05 mmol) in dichloromethane (5 mL) was added triethylamine (0.1 mL) and p-tolylsulfonyl isocyanate (0.012 mL, 0.08 mmol). The resultant solution was stirred at 0° C. for 1 hour and saturated aqueous sodium bicarbonate was added. The organic layer was washed with brine. The aqueous layer was extracted with dichloromethane and the combined organics were dried over sodium sulfate. Filtration and concentration followed by flash chromatography (5% methanol in dichloromethane) and recrystallization from dichloromethane-ether provided N-{[(4-{[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl)amino]carbonyl}-4-methylbenzenesulfonamide (14 mg, 35%) as a yellow solid. 1H NMR (CDCl3): δ 8.03 (m, 1 H), 7.84–7.76 (m, 3 H), 7.58 (d, 2 H), 7.36–7.26 (m, 5 H), 7.01 (d, 2 H), 6.66 (m, 1 H), 6.34 (m 1 H), 6.04 (m, 2 H), 4.36 (m, 1 H), 3.91 (s, 3 H), 3.38–3.30 (m, 4 H), 2.36 (s, 3 H), 2.07 (m, 2 H), 1.82–1.54 (m, 10 H); MS m/z 669 (M+1).

1. washThe organic layer was washed with brine
2. extractionThe aqueous layer was extracted with dichloromethane
3. dry with materialthe combined organics were dried over sodium sulfate
4. filtrationFiltration and concentration
5. customfollowed by flash chromatography (5% methanol in dichloromethane) and recrystallization from dichloromethane-ether