(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(3,5-dimethylphenylamino)pyridazin-3-ylamino)cyclohexylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-4-(3,5-dimethylphenylamino)pyridazine-3-carboxamide (44 mg, 159 μmol) in NMP (530 μL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (68.2 mg, 318 μmol) and the mixture heated to 140° C. for 20 h. Additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (68.2 mg, 318 μmol) was then added and heating continued for a further 7 h. Finally, another portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (34.1 mg, 159 μmol) was added and the mixture heated for 16 h. The reaction mixture was cooled, and then diluted with ethyl acetate. The phases were separated and the organic phase then washed with water and brine. The organic phase was collected, concentrated in vacuo, and the residue obtained was purified by chromatography (silica, 30 to 70% ethyl acetate in hexanes) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(3,5-dimethylphenylamino)pyridazin-3-ylamino)cyclohexylcarbamate (30 mg, 66.0 μmol, 42%) as a brown oil. MS (EI/CI) m/z: 455.2 [M+H].

Provenance & Evidence