反应详情

温度

140 °C

6-Chloro-4-(6-ethoxypyridin-2-ylamino)pyridazine-3-carboxamide (33 mg, 112 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (50 mg, 233 μmol) were combined in NMP (2 mL) and stirred at 140° C. for 48 h. A second portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (50 mg, 233 μmol) was added and the reaction was stirred at 140° C. for 96 h, then cooled to room temperature and concentrated in vacuo. The residue obtained was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc and the organics were combined and washed with brine. The solvent was removed in vacuo to give an orange foam. The foam was concentrated onto silica and purified by chromatography (4 g RediSep Gold, 0 to 5% of a mixture of MeOH containing 0.5% NH4OH in dichloromethane, 20 min) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-ethoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (32.3 mg, 51.4 μmol, 46%) containing some dichloromethane impurity. This was used directly without further purification. MS (EI/CI) m/z: 372.3 [M+H].

1. stirringthe reaction was stirred at 140° C. for 96 h
2. temperaturecooled to room temperature
3. concentrationconcentrated in vacuo
4. customThe residue obtained
5. customwas partitioned between water and EtOAc
6. extractionThe aqueous layer was extracted with EtOAc
7. washwashed with brine
8. customThe solvent was removed in vacuo
9. customto give an orange foam
10. concentrationThe foam was concentrated onto silica
11. custompurified by chromatography (4 g RediSep Gold, 0 to 5% of a mixture of MeOH containing 0.5% NH4OH in dichloromethane, 20 min)