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

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine (281 mg, 1.1 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (170 mg, 1.1 mmol) and DIPEA (1 mL, 5.5 mmol) in IPA (2 mL) was heated for 16 h at 90° C. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue 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 0-20% DCM in EtOAc) to afford 275 as a white solid (295 mg, 72%). LCMS (Method K): RT 3.37 min [M+H]+ 375.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.60 (1H, ddd, J=4.88, 1.91, 0.81 Hz), 8.06 (1H, td, J=7.75, 1.94 Hz), 7.86 (1H, s), 7.78-7.68 (3H, m), 7.50 (1H, ddd, J=7.52, 4.87, 0.98 Hz), 7.21-7.11 (4H, m), 5.87-5.78 (1H, m), 1.53 (3H, d, J=6.83 Hz)

Provenance & Evidence