Trifluoroacetic acid → HCID 90308645, compound

Participants

Reaction Steps

A vial was charged with tert-butyl N-[(4aR,11bR)-10-[(5-hydroxypyridine-2-carbonyl)amino]-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (150 mg, 0.233 mmol), cesium carbonate (152 mg, 0.465 mmol) and DMF (1163 μl). To this slurry was added 2-bromoacetonitrile (19.81 μl, 0.244 mmol), and the reaction was stirred at RT for 3 h. Water and EtOAc were added and the layers were separated. The organic portion was dried, filtered and concentrated. The crude material was dissolved in 1 mL DCM, and TFA (358 μl, 4.65 mmol) was added and the reaction was stirred for 1 h. EtOAc and saturated NaHCO3 were added, and the layers were separated. The organic portion was dried, filtered and concentrated. The crude product was purified by silica gel chromatography, using a gradient 0-50% 90/10 DCM/MeOH in DCM. The product was further purified by reverse phase chromatography on the Isolera using 0-75% 0.1% TFA/ACN in water solvent system followed by isolation using an SCX column to give N-((4aR,11bR)-2-amino-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-10-yl)-5-(cyanomethoxy)picolinamide. MS m/z=484.1 (M+H).

Provenance & Evidence