Trifluoroacetic acid → 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(4-methyl-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide

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Reaction Steps

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (27 mg, 55.6 μmol) in dichloromethane (1 mL) was added trifluoroacetic acid (127 mg, 85.7 μL, 1.11 mmol) and the mixture stirred at room temperature for 16 h. The mixture was concentrated in vacuo and then the residue was diluted with dichloromethane and 25% aqueous NH4OH. The mixture was washed with water (2×), then the organic phase was collected, concentrated in vacuo, and purified by chromatography (silica, 1 to 10% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane) to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(4-methyl-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (7 mg, 18.2 μmol, 33%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.61 (s, 1H), 8.38 (s, 1H), 8.10 (s, 1H), 7.68 (s, 1H), 6.98 (d, J=5.8 Hz, 1H), 6.71 (s, 1H), 6.61 (s, 1H), 4.08 (q, J=5.5 Hz, 1H), 3.92 (d, J=9.9 Hz, 1H), 3.81 (d, J=12.2 Hz, 1H), 3.59 (d, J=11.7 Hz, 1H), 3.47 (t, J=11.8 Hz, 1H), 3.28 (s, 1H), 3.17 (d, J=5.0 Hz, 2H), 2.67 (t, J=7.8 Hz, 1H), 2.33 (s, 1H), 2.26 (s, 3H), 1.72 (m, 3H), 1.23 (s, 1H), 0.93 (t, J=7.4 Hz, 3H); MS (EI/CI) m/z: 386.2 [M+H].

Provenance & Evidence