Diisopropylethylamine → 4-amino-6-[(S)-1-(7-bromo-1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamino]pyrimidine-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-1-(7-bromo-1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamine (80 mg, 0.27 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (41 mg, 0.27 mmol) and DIPEA (140 μL, 0.80 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 16 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) to afford 395 as a white solid (86 mg, 77%). LCMS (Method K): RT 4.10 min [M+H]+ 415.95. 1H NMR (CDCl3, 400 MHz): δ 8.20 (1H, s), 7.56 (1H, dd, J=8.73, 4.57 Hz), 7.10-7.04 (1H, m), 6.27 (1H, d, J=7.81 Hz), 6.06-5.98 (1H, m), 5.32 (2H, s), 3.52-3.46 (1H, m), 1.68 (3H, d, J=6.75 Hz), 1.45-1.33 (3H, m), 1.20-1.14 (1H, m)

Provenance & Evidence