Diisopropylethylamine → 4-Amino-6-[1-(6-fluoro-1-pyridin-4-yl-1H-benzoimidazol-2-yl)-ethylamino]-pyrimidine-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-(6-fluoro-1-pyridin-4-yl-1H-benzoimidazol-2-yl)ethylamine (55 mg, 0.22 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (33 mg, 0.22 mmol) and DIPEA (115 μL, 0.64 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the crude mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a gradient 5-60%, 0.1% NH4OH in acetonitrile/water) to afford 296 as a pale beige solid (21 mg, 26%). LCMS (Method K): RT 3.00 min [M+H]+ 375.06. 1H NMR (DMSO-d6, 400 MHz): δ 8.75-8.71 (2H, m), 7.88 (1H, s), 7.79-7.72 (2H, m), 7.65-7.60 (2H, m), 7.24-7.12 (3H, m), 7.06 (1H, dd, J=8.98, 2.49 Hz), 5.65-7.56 (1H, m), 1.57 (3H, d, J=6.77 Hz)

Provenance & Evidence