Diisopropylethylamine → tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate

Participants

Reaction Steps

To a solution of 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (784 mg, 2.2 mmol) in DCM (40 mL) was added PyBOP (1.46 g, 2.8 mmol) and the mixture stirred at room temperature for 30 min. A solution of N-(1-(4-Amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamide (647 mg, 2.0 mmol) and DIPEA (0.59 mL, 3.4 mmol) in DCM (40 mL) was then added and the mixture was stirred at room temperature for 16 hr. The mixture was diluted with DCM (60 mL) and washed with water (30 mL). The organic layer was separated, passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate as an off-white solid (1.32 g).

Provenance & Evidence