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

Participants

Reaction Steps

A mixture of (S)-1-[6-fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]-ethylamine.2HCl (118 mg, 0.34 mmol), 2-amino-4-chloropyrimidine-5-carbonitrile (40 mg, 0.26 mmol) and DIPEA (222 μL, 1.29 mmol) in IPA (0.75 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 into 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 DCM) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a gradient 5-75%, 0.1% NH4OH in acetonitrile/water) to afford 363 as a white solid (58 mg, 57%). LCMS (Method K): RT 3.10 min [M+H]+ 392.97. 1H NMR (DMSO-d6, 400 MHz): δ 8.66 (1H, d, J=2.64 Hz), 8.62 (1H, s), 8.06 (1H, s), 8.03 (1H, d, J=9.27 Hz), 7.76-7.75 (2H, m), 7.15 (1H, ddd, J=9.85, 8.79, 2.51 Hz), 7.08 (1H, dd, J=8.96, 2.50 Hz), 7.05-6.60 (2H, m), 5.56 (1H, m), 1.55 (3H, d, J=6.75 Hz)

Provenance & Evidence