(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → [(1S,2R)-2-(6-carbamoyl-5-p-tolylamino-pyridazin-3-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

6-Chloro-4-p-tolylamino-pyridazine-3-carboxylic acid amide (199 mg, 0.758 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (325 mg, 1.52 mmol) were dissolved in N-methylpyrrolidinone (4.7 mL). The reaction mixture was heated at 150° C. for 16 h, then additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (550 mg, 2.57 mmol total) was added in three portions over 6 d. The reaction mixture was cooled, diluted with ethyl acetate and saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate. The combined organic extracts were washed with water and brine, then dried (sodium sulfate), filtered, and concentrated in vacuo. The residue obtained was purified by chromatography (silica, 0 to 5% methanol in dichloromethane) to give [(1S,2R)-2-(6-carbamoyl-5-p-tolylamino-pyridazin-3-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester (26 mg, 8%) as a light brown amorphous residue. LCMS (EI/CI) m/z: 441 [M+H].

Provenance & Evidence