(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689799, compound

Participants

Reaction Conditions

Reaction Steps

A dry 50 mL round bottom flask was charged with 6-chloro-4-(6-(2-hydroxypropan-2-yl)pyridin-2-ylamino)pyridazine-3-carboxamide (241 mg, 783 μmol) dissolved in NMP (2.00 mL) To this solution was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (168 mg, 783 μmol) and the reaction mixture was heated in an oil bath with stirring at 120° C. for 18 h. After that, it was added more tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (168 mg, 783 μmol) in small portions during 7 hours. After last addition, the reaction was continued for 18 h. After cooling to room temperature, the solvent was distilled off under high vacuum, the residue was dissolved in dichloromethane containing few drops of methanol and then purified by flash chromatography (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-hydroxypropan-2-yl)pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (179 mg, 47.1% yield) as a yellow foam. 1H NMR (CHLOROFORM-d) δ: 11.54 (br. s., 1H), 8.16 (br. s., 1H), 8.04 (s, 1H), 7.60 (t, J=7.9 Hz, 1H), 7.05 (d, J=7.6 Hz, 1H), 6.76 (d, J=8.3 Hz, 1H), 6.53-6.70 (m, 1H), 5.81 (d, J=3.4 Hz, 1H), 5.43 (br. s., 1H), 3.71-4.14 (m, 3H), 1.23-1.90 (m, 23H); LC-MS 486.2 [M+H]+.

Provenance & Evidence