Diisopropylethylamine → 2-Amino-4-{(S)-1-[6-fluoro-1-(5-fluoro-pyridin-3-yl)-1H-benzoimidazol-2-yl]-ethylamino}-6-methyl-pyrimidine-5-carbonitrile

Participants

Reaction Steps

A mixture of (S)-1-[6-fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]-ethylamine.2HCl (165 mg, 0.48 mmol), 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (60 mg, 0.36 mmol) and DIPEA (315 μL, 1.82 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 18 h. After cooling to RT, the reaction 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 0-100% EtOAc in cyclohexane) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a gradient 5-75%, 0.1% NH4OH in acetonitrile/water) to afford 364 as a white solid (21 mg, 15%). LCMS (Method K): RT 3.04 min [M+H]+ 407.04. 1H NMR (DMSO-d6, 400 MHz): δ 8.66 (1H, d, J=2.64 Hz), 8.61 (1H, d, J=1.63 Hz), 8.02 (1H, d, J=9.22 Hz), 7.77 (1H, dd, J=8.80, 4.84 Hz), 7.55 (1H, d, J=7.75 Hz), 7.15 (1H, ddd, J=9.84, 8.79, 2.50 Hz), 7.07 (1H, dd, J=8.96, 2.48 Hz), 7.05-6.58 (2H, m), 5.53 (1H, m), 2.18 (3H, s), 1.54 (3H, d, J=6.75 Hz)

Provenance & Evidence