反应详情

To a solution of 5-(4-chloro-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (300 mg, 0.805 mmol), [6-(trifluoromethyl)-2-pyridinyl]acetic acid (90 wt %) (183 mg, 0.805 mmol), HATU (306 mg, 0.805 mmol), in N,N-Dimethylformamide (DMF) (50 mL) under nitrogen at 0° C. was added DIEA (0.562 mL, 3.22 mmol). The reaction was stirred overnight at room temperature, then poured into water and stirred for one hour. A brown precipitate formed which was collected by filtration and washed with water. The solid was dissolved in ca. 25 mL chloroform, and purified by flash chromatography (0-100% EtOAc in chloroform→0-10% MeOH in EtOAc, 24-g column) to afford 5-(4-chloro-1-{[6-(trifluoromethyl)-2-pyridinyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (161.5 mg) as an off-white solid. LC-MS (ES) m/z=487 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.22-3.30 (m, 2H), 3.74 (s, 3H), 4.22 (s, 2H), 4.37 (t, J=8.34 Hz, 2H), 5.72-6.02 (m, 2H), 7.18-7.25 (m, 2H), 7.71 (d, J=7.83 Hz, 1H), 7.83 (d, J=7.58 Hz, 1H), 8.01 (d, J=8.34 Hz, 1H), 8.10 (t, J=7.96 Hz, 1H), 8.13 (s, 1H).

1. stirringstirred for one hour
2. customA brown precipitate formed which
3. filtrationwas collected by filtration
4. washwashed with water
5. dissolutionThe solid was dissolved in ca. 25 mL chloroform
6. custompurified by flash chromatography (0-100% EtOAc in chloroform→0-10% MeOH in EtOAc, 24-g column)