Trifluoroacetic acid → 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazine-3-carboxamide

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Reaction Steps

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (100 mg, 200 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (456 mg, 308 μL, 4.00 mmol) and the mixture stirred at room temperature for 16 h. The mixture was concentrated in vacuo then 25% aqueous NH4OH solution added. This was then diluted with dichloromethane and water, the phases separated, and the organic phase washed twice with water. The organic layer was dried over anhydrous magnesium sulfate then purified by chromatography (silica, 0 to 15% methanol in dichloromethane) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazine-3-carboxamide (43 mg, 108 μmol, 54%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.45 (s, 1H), 8.31 (s, 1H), 7.69 (s, 1H), 7.58 (s, 1H), 7.42 (d, J=8.7 Hz, 1H), 6.85 (d, J=8.7 Hz, 1H), 6.63 (d, J=8.0 Hz, 1H), 3.80 (s, 3H), 3.42 (m, 1H), 3.15 (s, 1H), 1.52-1.69 (m, 8H), 1.32 (m, 2H), 1.24 (d, J=6.4 Hz, 6H); MS (EI/CI) m/z: 400.3 [M+H].

Provenance & Evidence