Morpholine → 4-{6-Iodo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(2-aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid (3 g, 7.87 mmol)) in DCM (40 mL), was added thionyl chloride (6.85 ml, 94.46 mmol) followed by DMF (catalytic, 3 drops). The mixture was stirred at 50° C. for 1 hour. The reaction mixture was concentrated in vacuo and DCM added and the concentration repeated (×2). The crude acid chloride (assumed 7.87 mmol) was suspended in more DCM (30 mL) and morpholine (1.37 ml, 15.74 mmol) was added at 0 dropwise. The reaction was stirred at RT overnight. The reaction mixture was diluted with more DCM (25 ml) and 2M Na2CO3 added (35 ml). A pale brown precipitate was collected by filtration and washed with more DCM. The precipitate was slurried in water:acetonitrile (3:1, 10 ml) and the off-white solid collected by filtration and washed with more water:acetonitrile (3:1, 2×1 ml). The solid was then dried under vacuum to give the title compound (2.72 g, LC-MS purity=86%): 1H NMR (500 MHz, DMSO) delta 3.41-3.76 (6H, m), 3.85-3.97 (2H, m), 7.05 (1H, d, J=5.5 Hz), 7.18 (2H, s), 7.74 (1H, dd, J=8.4, 1.1 Hz), 7.80 (1H, d, J=8.4 Hz), 8.34 (1H, d, J=5.5 Hz), 9.33 (1H, s); LC-MS: m/z=+450.90 (M+H)+.

Provenance & Evidence