反应详情

A slurry of 2,4-dichloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (10 g, 29.2 mmol) and 2-amino-4,6-difluorobenzoic acid (source: Buttpark Ltd.) (5.06 g, 29.2 mmol) in iPrOH (250 ml) and DIPEA (25.5 ml, 146 mmol) was heated at 95° C. overnight, then distilled 180 mL of solvent off over 4 h, then heated for another 2 h. After allowing to cool to rt, the reaction mixture was diluted with EtOAc (300 mL), washed with a 1N HCl solution (400 mL), a saturated NaHCO3 solution (200 mL), a saturated NaCl solution (200 mL). The organic layer was diluted with Et2O (200 mL). The resulting slurry was filtered, the solid dried in vacuum oven overnight at 80° C. to obtain 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzoic acid as a pale yellow solid (5.3 g, 38%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.37 (s, 3H), 6.60-6.78 (m, 2H), 7.48 (d, J=8.06 Hz, 2H), 7.77 (d, J=3.85 Hz, 1H), 7.98 (d, J=8.42 Hz, 2H), 8.23-8.36 (m, 1H); ESIMS (M+H)+=478.94.

1. distillationdistilled 180 mL of solvent off over 4 h
2. temperatureheated for another 2 h
3. additionthe reaction mixture was diluted with EtOAc (300 mL)
4. washwashed with a 1N HCl solution (400 mL)
5. additionThe organic layer was diluted with Et2O (200 mL)
6. filtrationThe resulting slurry was filtered
7. customthe solid dried in vacuum oven overnight at 80° C.