Diisopropylethylamine → 4-Amino-6-[(S)-1-(6-fluoro-7-methyl-1-pyridin-2-yl-1H-benzoimidazol-2-yl)-ethylamino]-pyrimidine-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-1-(6-fluoro-7-methyl-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (300 mg, 0.87 mmol) in IPA (10 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (135 mg, 0.87 mmol) and DIPEA (448 μL, 2.62 mmol) and the reaction mixture heated at 90° C. for 16 h. The reaction mixture was concentrated in vacuo and the resultant residue subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc). The product was triturated with diethyl ether then subjected to HPLC purification (C18, 10-90% MeCN in H2O, 0.1% formic acid, 20 min gradient) to give 289 as a white solid (164 mg, 48%). 1H NMR 400 MHz 6 (DMSO-d6): 8.55 (1H, br s), 8.00-7.91 (1H, m), 7.81-7.73 (1H, m), 7.70-7.60 (1H, m), 7.53 (1H, dd, J=8.7, 4.6 Hz), 7.55-7.45 (1H, m), 7.21-7.09 (1H, m), 7.06 (1H, dd, J=10.3, 8.7 Hz), 5.65-5.13 (1H, m), 1.63 (3H, s), 1.46 (3H, d, J=6.7 Hz). LCMS (Method K): RT=3.40 min, [M+H]+=389

Provenance & Evidence