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

Participants

Reaction Steps

A mixture of (S)-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine.2HCl (164 mg, 0.50 mmol), 2-amino-4-chloropyrimidine-5-carbonitrile (77 mg, 0.50 mmol) and DIPEA (427 μL, 2.49 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 17 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 trituration from Et2O to afford 367 as a white solid (72 mg, 39%). LCMS (Method K): RT 3.06 min [M+H]+ 375.00. 1H NMR (DMSO-d6, 400 MHz): δ 8.59 (1H, m), 8.06 (2H, m), 7.77 (2H, m), 7.68 (1H, d, J=7.41 Hz), 7.48 (1H, m), 7.19-6.80 (4H, m), 5.85 (1H, m), 1.52 (3H, d, J=6.81 Hz

Provenance & Evidence