(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689795, compound

Participants

Reaction Conditions

Reaction Steps

A resealable pressure tube was charged with 6-chloro-4-(6-(2-cyanopropan-2-yl)pyridin-2-ylamino)pyridazine-3-carboxamide (200 mg, 631 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (135 mg, 631 μmol) in NMP (2.00 mL). The reaction mixture was heated in an oil bath with stirring at 120° C. for 18 h. Then added more tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (135 mg, 631 μmol) in small portions during 7 hours and reaction continued for 18 h. The solvent was distilled off under high vacuum. The residue was dissolved in dichloromethane containing few drops of methanol and then purified by flash column (spherical silica 20-45 μM, 50 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2 to yield tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-(2-cyanopropan-2-yl)pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (110 mg, 222 μmol, 35.2% yield) as a yellow foam. 1H NMR (CHLOROFORM-d) δ: 11.48 (s, 1H), 8.82 (br. s., 1H), 8.00-8.11 (m, 1H), 7.62 (t, J=7.9 Hz, 1H), 6.89 (d, J=7.6 Hz, 1H), 6.79 (d, J=8.3 Hz, 1H), 5.53-5.85 (m, 2H), 5.06 (d, J=8.3 Hz, 1H), 4.47 (br. s., 1H), 3.80-3.99 (m, 1H), 1.24-1.93 (m, 23H); LC-MS 495.1 [M+H]+.

Provenance & Evidence