反应详情

温度

90 °C

A mixture of 4-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-3-morpholinecarboxamide (360 mg, 1.05 mmol) and hydrazine monohydrate (2.58 mL, 52.6 mmol) in ethanol (10 mL) was stirred at 90° C. in a sealed tube for 16 hours. The mixture was cooled and diluted with water. Attempts to extract the product from the water using 90/10 CH2Cl2/IPA were unsuccessful, so the aqueous phase was combined with the residue from the concentrated CH2Cl2/IPA extractions and the mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (68 g SiO2, CHCl3 to 80/20/2 CHCl3/CH3OH/NH4OH gradient with a 10 minute hold at 90/10/1 CHCl3/CH3OH/NH4OH) to give the title compound (40 mg) as an off-white solid. LC-MS (ES) m/z=355 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 3.29-3.41 (m, 1H), 3.41-3.50 (m, 1H), 3.61 (dd, J=11.6, 3.5 Hz, 1H), 3.85-3.93 (m, 1H), 3.99-4.18 (bs, 1H), 4.35 (d, J=11.6 Hz, 1H), 4.82-5.08 (bs, 1H), 5.39 (s, 2H), 6.12 (s, 2H), 6.55 (s, 1H), 7.19 (s, 1H), 7.35 (s, 1H), 7.57 (d, J=8.3 Hz, 1H), 7.72 (d, J=8.6 Hz, 1H), 7.95 (s, 1H), 11.54 (s, 1H).

1. temperatureThe mixture was cooled
2. extractionto extract the product from the water using 90/10 CH2Cl2/IPA
3. extractionwas combined with the residue from the concentrated CH2Cl2/IPA extractions
4. concentrationthe mixture was concentrated in vacuo
5. customThe residue was purified by silica gel chromatography (68 g SiO2, CHCl3 to 80/20/2 CHCl3/CH3OH/NH4OH gradient with a 10 minute hold at 90/10/1 CHCl3/CH3OH/NH4OH)