(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-butyl (1S,2R)-2-(5-(6-(1H-pyrazol-1-yl)pyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(6-(1H-pyrazol-1-yl)pyridin-2-ylamino)-6-chloropyridazine-3-carboxamide (131 mg, 415 μmol) in NMP (5 mL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (133 mg, 622 μmol) and the mixture stirred at 140° C. for 24 h. A second portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (162 mg, 756 μmol) was added and the mixture heated at 140° C. for a further 24 h. The reaction mixture was cooled, and then diluted with water. The mixture was extracted with ethyl acetate (3×50 mL) then the combined organic phases were washed with brine (50 mL), then concentrated in vacuo, and finally purified by chromatography (silica, 12 g RediSep Gold, 2 to 6% of a 99.5:0.5 methanol:ammonium hydroxide solution in dichloromethane, 20 min) to give tert-butyl (1S,2R)-2-(5-(6-(1H-pyrazol-1-yl)pyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate (70 mg, 142 μmol, 34%) as a beige solid. MS (EI/CI) m/z: 494.3 [M+H].

Provenance & Evidence