Diisopropylethylamine → tert-butyl N-[2-bromo-4-[[5-[2-(tert-butoxycarbonylamino)-8-oxabicyclo[3.2.1]octan-5-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate

Participants

Reaction Steps

To a solution of tert-butyl N-[5-fluoro-2-hydroxy-5-(2-methyl-4-nitro-pyrazol-3-yl)cycloheptyl]carbamate (210 mg, 0.565 mmol, intermediate 64) in THF (20 mL) and MeOH (20 mL) was added 10% palladium on carbon (20 mg). The reaction mixture was heated at 40° C. under a 400 psi atmosphere of hydrogen for 3 hr. After cooling to room temperature, the mixture was filtered through Celite®, washing with MeOH (50 mL) and concentrated under reduced pressure. To a solution of the residue in DCM (30 mL) was added DIPEA (2 mL, 1.40 mmol), 2-bromo-5-(tert-butoxycarbonylamino)thiazole-4-carboxylic acid (208 mg, 0.62 mmol, Example 22) and PyBOP (727 mg, 1.40 mmol) and the mixture was stirred at room temperature for 18 hr. Water (20 mL) was added and the mixture was extracted with DCM (100 mL). The organic layer was passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel chromatography (80-100% EtOAc/isohexane) gave tert-butyl N-[2-bromo-4-[[5-[2-(tert-butoxycarbonylamino)-8-oxabicyclo[3.2.1]octan-5-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (120 mg, 34% over two steps). 1H NMR (400 MHz, CDCl3) δ 10.40 (br s, 1H), 9.86 (br s, 1H), 8.12 (br s, 1H), 4.70-4.63 (m, 1H), 4.36-4.22 (m, 1H), 3.97-3.86 (m, 1H), 3.86 (s, 3H), 2.40-2.31 (m, 1H), 2.21-1.93 (m, 7H), 1.55 (s, 9H), 1.52 (s, 9H).

Provenance & Evidence