2-Amino-4-chloro-6-methylpyrimidine → 4-(6-bromo-3-methyl-1H-indazol-1-yl)-6-methylpyrimidin-2-amine

Participants

Reaction Steps

To a solution of 6-bromo-3-methyl-1H-indazole (500 mg, 2.37 mmol) in dry DMF (5 mL) at 0° C. under an atmosphere of nitrogen was introduced sodium hydride (684 mg of a 60% dispersion in mineral oil, 7.11 mmol). After warming to RT for 30 minutes, 4-chloro-6-methylpyrimidin-2-amine (510 mg, 3.55 mmol) was added and the solution warmed to 65° C. for 18 hr. The reaction mixture was cooled to RT, quenched by dropwise addition of water (5 mL) and extracted with 2:1 chloroform/isopropanol (3×10 mL extractions). The combined organic extracts were washed with water (5 mL) and brine (5 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by column chromatography (Biotage, DCM containing a 0-10% gradient of methanol) furnished a yellow semi-solid which was slurried in acetonitrile (3 mL). The precipitate was collected by filtration to furnish the title compound as a yellow solid: 1H NMR (500 MHz, DMSO) delta 2.29 (3H, s), 2.56 (3H, s), 6.79-6.93 (2H, m), 6.93-6.95 (1H, m), 7.48 (1H, dd, J=8.43, 1.66 Hz), 7.78 (1H, d, J=8.35 Hz), 9.07 (1H, d, J=1.42 Hz); LC-MS: m/z=+317.95/319.95.

Provenance & Evidence