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

Participants

Reaction Conditions

Reaction Steps

6-Chloro-4-(6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (289 mg, 991 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (425 mg, 1.98 mmol) were dissolved in N-methyl-2-pyrrolidinone (2 mL) and heated at 130° C. for 24 h. LCMS showed desired product mass, as well as starting material. A third equivalent of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate was added (213 mg, 0.991 mmol) and heating continued. After 8 h, a third portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (0.310 g) was added. After 24 h, the mixture was cooled and concentrated in vacuo (high vacuum, 100° C.) to a brown solid residue. Purification by chromatography (silica, 0 to 10% of a 9:1 MeOH:NH4OH solution in dichloromethane, 20 min) gave tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (271 mg, 577 μmol, 58%) as a light brown solid. LC-MS 470.2 [M+H]+.

Provenance & Evidence