Triphenylphosphine dibromide → tert-Butyl N-[[4-[5-(2-amino-5-bromo-3-pyridyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate

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Reaction Steps

tert-Butyl N-[[4-[[(2-amino-5-bromo-pyridine-3-carbonyl)amino]carbamoyl]phenyl]methyl]-N-methyl-carbamate (992.3 mg, 2.074 mmol) was dissolved in dry MeCN (15 mL) and cooled in an ice bath under a nitrogen atmosphere. DIPEA (804.2 mg, 1.084 mL, 6.222 mmol) was added via syringe followed by dibromo(triphenyl)phosphorane (1.185 g, 2.696 mmol) portionwise and the reaction allowed to warm to ambient temperature over 15 hours. A further portion of MeCN (15 mL) and dibromo(triphenyl)phosphorane (437.7 mg, 1.037 mmol) were added and the reaction mixture stirred at ambient temperature for a 10 minutes. The precipitate was isolated by filtration and the filtrate concentrated in vacuo. The filtrate was re-dissolved in MeCN (15 mL) and cooled to 0° C. DIPEA (804.2 mg, 1.084 mL, 6.222 mmol) was added followed by dibromo(triphenyl)phosphorane (437.7 mg, 1.037 mmol) and the reaction mixture stirred at 0° C. for 30 minutes. The reaction mixture was concentrated in vacuo and the resultant residue purified by column chromatography (ISCO Companion™, 40 g column, 0-50% EtOAc/Petroleum ether) and the product containing fractions concentrated in vacuo. The residue was combined with the previously obtained precipitate to give the sub-title product as a white solid (682 mg, 63% Yield corrected for residual OPPh3). 1H NMR (400.0 MHz, DMSO) δ 1.39-1.46 (d, 9H), 4.48 (d, J=10.5 Hz, 2H), 7.46 (d, J=8.1 Hz, 2H), 8.22 (d, J=8.2 Hz, 2H), 8.32 (d, J=2.4 Hz, 1H) and 8.49 (d, J=2.4 Hz, 1H) ppm; MS (ES+) 462.1.

Provenance & Evidence