Trifluoroacetic acid → HCID 178461936, 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 (187 mg, 0.52 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, 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (126 mg, 0.53 mmol) and DIPEA (280 μL, 1.59 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 24 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 DCM) followed by trituration with EtOAc to afford 403 as a pale brown solid (98 mg, 50% over 2 steps). LCMS (Method K): RT 2.84 min [M+H]+ 378.03. 1H NMR (DMSO-d6, 400 MHz): δ 8.21-8.11 (2H, m), 7.94-7.81 (2H, m), 7.75-7.66 (1H, m), 7.19-7.08 (2H, m), 6.61 (1H, d, J=2.29 Hz), 5.89-5.73 (1H, m), 3.89 (3H, s), 1.61 (3H, d, J=6.84 Hz)

Provenance & Evidence