Diisopropylethylamine → 4-amino-6-[[(1S)-1-[1-cyclopropyl-6-fluoro-7-(morpholine-4-carbonyl)benzimidazol-2-yl]ethyl]amino]pyrimidine-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of [2-((S)-1-aminoethyl)-3-cyclopropyl-5-fluoro-3H-benzoimidazol-4-yl]-morpholin-4-yl-methanone (106 mg, 0.32 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (54 mg, 0.35 mmol) and DIPEA (170 μL, 0.98 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 0-10% MeOH in EtOAc) followed by trituration with EtOAc to afford 401 as a white solid (60 mg, 31%). LCMS (Method K): RT 2.81 min [M+H]+ 451.06. 1H NMR (CDCl3, 400 MHz): δ 8.18 (1H, s), 7.71-7.65 (1H, m), 7.05-6.97 (1H, m), 6.47-6.40 (0.7H, m), 6.15-6.05 (0.3H, m), 5.98-5.88 (1H, m), 5.38-5.31 (2H, m), 4.22-4.14 (1H, m), 3.93-3.72 (4H, m), 3.69-3.52 (2H, m), 3.44-3.33 (2H, m), 1.73 (1H, d, J=6.78 Hz), 1.65 (2H, d, J=6.76 Hz), 1.43-1.24 (2H, m), 1.11-0.93 (1H, m), 0.86-0.69 (1H, m)

Provenance & Evidence