反应详情

温度

0 °C

{(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrazol-3-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (34 mg, 0.079 mmol) was dissolved in dichloromethane (1 mL) then cooled to 0° C. Trifluoroacetic acid (0.5 mL, 6.49 mmol) was added drop-wise then the reaction mixture was warmed to 25° C. After 4 h, the mixture was cooled in an ice bath and neutralized with sodium bicarbonate solution. The mixture was extracted with ethyl acetate, and the combined organic layers washed with brine, dried (sodium sulfate), filtered, and concentrated in vacuo. Purification by chromatography (silica, 0 to 80% of a 0.1:0.01 solution of methanol:NH4OH in dichloromethane) gave 6-((1R,2S)-2-amino-cyclohexylamino)-4-(1-methyl-1H-pyrazol-3-ylamino)-pyridazine-3-carboxylic acid amide (5 mg, 20%) as a brown solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.84-10.89 (m, 1H) 8.23-8.32 (m, 1H) 7.66 (d, J=2.3 Hz, 1H) 7.48-7.59 (m, 1H) 7.10 (s, 1H) 6.73 (d, J=7.9 Hz, 1H) 6.05 (d, J=2.3 Hz, 1H) 3.91-4.05 (m, 1H) 3.01-3.11 (m, 1H) 1.46-1.72 (m, 6H) 1.25-1.36 (m, 2H); LCMS (EI/CI) m/z: 331 [M+H].

1. temperaturethe reaction mixture was warmed to 25° C
2. temperaturethe mixture was cooled in an ice bath
3. extractionThe mixture was extracted with ethyl acetate
4. washthe combined organic layers washed with brine
5. dry with materialdried (sodium sulfate)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification by chromatography (silica, 0 to 80% of a 0.1:0.01 solution of methanol