反应详情

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-methoxy-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (96 mg, 192 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (438 mg, 296 μL, 3.84 mmol) and the mixture stirred at room temperature overnight. The mixture was concentrated in vacuo then diluted with 25% aqueous NH4OH and dichloromethane. The phases were separated and the organic phase washed with water. The organic layer was concentrated in vacuo then purified by chromatography (silica, 3 to 20% methanol in dichloromethane) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(5-methoxy-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (59 mg, 148 μmol, 77%) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.36 (s, 1H), 8.30 (s, 1H), 7.72 (s, 1H), 7.60 (s, 1H), 7.42 (d, J=8.8 Hz, 1H), 6.87 (d, J=8.8 Hz, 1H), 6.72 (d, J=7.6 Hz, 1H), 3.96 (s, 1H), 3.79 (s, 3H), 3.28 (s, 1H), 2.72 (t, J=7.3 Hz, 2H), 1.54-1.74 (m, 8H), 1.35 (m, 2H), 0.94 (t, J=7.4 Hz, 3H); MS (EI/CI) m/z: 400.2 [M+H].

1. concentrationThe mixture was concentrated in vacuo
2. additionthen diluted with 25% aqueous NH4OH and dichloromethane
3. customThe phases were separated
4. washthe organic phase washed with water
5. concentrationThe organic layer was concentrated in vacuo
6. customthen purified by chromatography (silica, 3 to 20% methanol in dichloromethane)