Trifluoroacetic acid → HCID 68158045, compound

Participants

Reaction Steps

TFA (1 mL) was added to a stirring solution of {(S)-1-[6-fluoro-1-(1-methyl-1H-pyrazol-3-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl ester (126 mg, 0.35 mmol) in DCM (3 mL). After stirring at RT for 3 h, 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 and concentrated in vacuo to give a brown oil. A mixture of this residue, 4-amino-6-chloropyrimidine-5-carbonitrile (60 mg, 0.39 mmol) and DIPEA (205 μL, 1.17 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the crude 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 402 as a white solid (71 mg, 54% over 2 steps). LCMS (Method K): RT 3.27 min [M+H]+ 378.04. 1H NMR (DMSO-d6, 400 MHz): δ 7.97 (1H, s), 7.91 (1H, d, J=2.31 Hz), 7.73 (1H, dd, J=8.66, 4.85 Hz), 7.61 (1H, d, J=7.64 Hz), 7.25 (2H, s), 7.17-7.08 (2H, m), 6.54 (1H, d, J=2.31 Hz), 5.77-5.67 (1H, m), 3.89 (3H, s), 1.52 (3H, d, J=6.87 Hz)

Provenance & Evidence