反应详情

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-cyclopropylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (25 mg, 53.5 μmol) in dichloromethane (4 mL) was added TFA (370 μg, 0.25 μL, 3.24 μmol). After 6 h, the mixture was concentrated in vacuo, then purified by flash chromatography (spherical silica, 20-45 μm, 25 g, Versaflash from Supelco, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-cyclopropylpyridin-2-ylamino) pyridazine-3-carboxamide (13 mg, 10%, two steps) as a brown solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 11.43 (br. s., 1H) 8.17 (br. s., 1H) 8.03 (br. s., 1H) 7.44 (br. s., 1H) 7.03 (br. s., 1H) 6.80 (br. s., 1H) 6.60 (br. s., 1H) 5.76 (br. s., 1H) 5.49 (br. s., 1H) 3.82 (br. s., 1H) 3.24 (br. s., 1H) 2.03 (br. s., 1H) 1.32-1.91 (m, 8H) 1.05 (d, J=16.62 Hz, 4H). LCMS (EI/CI) m/z: 368 [M+H].

1. concentrationthe mixture was concentrated in vacuo
2. custompurified by flash chromatography (spherical silica, 20-45 μm, 25 g, Versaflash from Supelco, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min)