Nitrogen → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-4-(5-fluoro-6-methylpyridin-2-ylamino) pyridazine-3-carboxamide (109 mg, 387 μmol) in N-methyl-2-pyrrolidinone (2.4 mL) was added DMAP (50.7 mg, 406 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (166 mg, 774 μmol) and the mixture was heated to 150° C. for 1.5 d. A steam of N2 was blown into the mixture while still heating at 140° C. to evaporate the NMP, then the reaction mixture was purified by chromatography (silica, 50 μm, 40 g, Analogix, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min) to provide tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (82 mg, 23%) as a brown oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 11.43 (s, 1H) 8.24 (s, 1H) 8.08 (br. s., 2H) 7.22-7.37 (m, 1H) 6.66-6.77 (m, 1H) 5.64 (d, J=3.28 Hz, 1H) 4.02 (br. s., 2H) 2.49 (d, J=3.03 Hz, 3H) 1.67-1.92 (m, 2H) 1.35-1.65 (m, 8H). LCMS (EI/CI) m/z: 460 [M+H].

Provenance & Evidence