反应详情

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-methoxy-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (77 mg, 154 μmol) in dichloromethane (2.4 mL) was added trifluoroacetic acid (350 mg, 237 μL, 3.07 mmol) and the mixture stirred at room temperature. After 16 h the mixture was concentrated in vacuo then diluted with 25% aqueous NH4OH and dichloromethane. The mixture was washed with water, then the organic phase was concentrated in vacuo and purified by chromatography (silica, 3 to 10% methanol in dichloromethane) to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5-methoxy-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (33 mg, 82.2 μmol, 54%) as a an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.37 (s, 1H), 8.33 (s, 1H), 7.74 (s, 1H), 7.58 (s, 1H), 7.41 (d, J=8.7 Hz, 1H), 6.87 (d, J=8.8 Hz, 1H), 6.76 (d, J=7.6 Hz, 1H), 3.98 (br. s, 1H), 3.84 (m, 1H), 3.79 (s, 3H), 3.70 (d, J=11.3 Hz, 1H), 3.51 (d, J=11.5 Hz, 1H), 3.40 (t, J=11.2 Hz, 1H), 2.99 (s, 1H), 2.72 (t, J=7.4 Hz, 2H), 1.81 (m, 1H), 1.72 (m, 2H), 1.72 (m, 3H), 0.94 (t, J=7.3 Hz, 3H); MS (EI/CI) m/z: 402.2 [M+H].

1. concentrationAfter 16 h the mixture was concentrated in vacuo
2. additionthen diluted with 25% aqueous NH4OH and dichloromethane
3. washThe mixture was washed with water
4. concentrationthe organic phase was concentrated in vacuo
5. custompurified by chromatography (silica, 3 to 10% methanol in dichloromethane)