Trifluoroacetic acid → 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazine-3-carboxamide

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Reaction Steps

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (100 mg, 204 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (466 mg, 315 μL, 4.1 mmol) and the mixture stirred at room temperature for 16 h. The mixture was diluted with 25% aqueous NH4OH, dichloromethane, and water. The organic phase was separated and washed with water (2×), then concentrated in vacuo and purified by chromatography (silica, 3 to 10% methanol in dichloromethane) to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazine-3-carboxamide (39 mg, 100 μmol, 49%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.76 (s, 1H), 8.39 (s, 1H), 7.85 (s, 1H), 7.65 (s, 1H), 7.60 (t, J=9.2 Hz, 1H), 6.88 (dd, J=8.9, 2.9 Hz, 1H), 6.78 (d, J=7.7 Hz, 1H), 3.96 (br. s, 1H), 3.80 (m, 1H), 3.70 (dd, J=11.4, 2.8 Hz, 1H), 3.49 (dd, J=11.4. 1.7 Hz, 1H), 3.37 (m, 2H), 2.96 (s, 1H), 1.80 (m, 1H), 1.69 (m, 2H), 1.29 (d, J=6.8 Hz, 6H); MS (EI/CI) m/z: 390.2 [M+H].

Provenance & Evidence