反应详情

温度

70 °C

The tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate (2.0 g, 4.76 mmol, Eq: 1.00) was dissolved in the solvent mixture of formic acid (40.0 ml) and formaldehyde, 37% (80.0 ml). The reaction mixture was stirred at 70° C. overnight until reaction was complete as determined by LCMS analysis, then cooled to ambient temperature. Water was added and the resultant aqueous mixture was washed with CH2Cl2 and the CH2Cl2 layer was discarded. The pH of the aqueous layer was adjusted to pH=12 carefully with solid K2CO3, which resulted in precipitation of a solid. The solid was collected by filtration, washed with water and dried in vacuum oven at 50° C. over 72 h to afford 1.4 g of the desired product. (M+H)+=334 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.84 (dd, J=8.31, 3.02 Hz, 4 H) 1.99-2.19 (m, 2 H) 2.35 (s, 3 H) 2.42-2.68 (m, 1 H) 3.02 (d, J=12.09 Hz, 2 H) 3.81 (s, 3 H) 6.86 (d, J=8.31 Hz, 1 H) 7.52 (dd, J=8.50, 2.46 Hz, 1 H) 8.16-8.33 (m, 3 H).

1. temperaturecooled to ambient temperature
2. washthe resultant aqueous mixture was washed with CH2Cl2
3. customresulted in precipitation of a solid
4. filtrationThe solid was collected by filtration
5. washwashed with water
6. customdried in vacuum oven at 50° C. over 72 h