Sodium hydride → 2-[1-(2-amino-5-chloropyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-ol

Participants

Reaction Steps

To a solution of 2-(6-iodo-1H-indazol-3-yl)propan-2-ol (300 mg, 0.99 mmol) in dry DMF (10 mL) at 0° C. under an atmosphere of nitrogen was introduced sodium hydride (63 mg of a 60% dispersion in mineral oil, 1.59 mmol). After 20 minutes at this temperature, 4,5-dichloropyrimidin-2-amine (326 mg, 1.99 mmol) was added and the solution warmed to RT for 10 minutes, then to 65° C. for 18 hr. Following cooling to RT, the reaction mixture was re-treated with additional sodium hydride (24 mg of a 60% dispersion in mineral oil) then warmed to 75° C. under nitrogen for 6 hr. The reaction mixture was cooled to RT, quenched carefully with water (20 mL) and extracted with EtOAc (2×20 mL extractions). The organic extracts were combined, dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by silica gel flash column chromatography (4:1 to 1:1 heptane/EtOAc gradient) furnished the title compound as an off-white solid: 1H NMR (500 MHz, CDCl3) delta 1.79 (6H, s), 5.19 (2H, br. s.), 7.61 (1H, dd, J=8.35, 1.42 Hz), 7.76 (1H, d, J=8.51 Hz), 8.42 (1H, s), 8.64 (1H, d, J=0.95 Hz); LC-MS: m/z=+429.90/431.65 (M+H)+.

Provenance & Evidence