Trifluoroacetic acid → HCID 118059798, compound

Participants

Reaction Conditions

Reaction Steps

To a 50-mL flask was added sodium triacetoxyborohydride (1.06 g, 5.0 mmol, 1.0 equiv.), trifluoroacetic acid (TFA, 2.0 mL, 26 mmol) and tetrahydrofuran (THF, 1.0 mL) at ambient temperature. This mixture was cooled to −5° C. under N2 and stirred at 0-5° C. for 10 min. To this solution was added 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (0.171 g, 5.0 mmol; Step D) and tert-butyl allyl{[allyl(2-oxoethy)amino]sulfonyl}carbamate (0.398 g, 2.5 mmol, 0.5 equiv.) in THF (1.5 mL) drop-wise at 0-5° C. over 5 min. The resulting reaction mixture was stirred under N2 at 0-5° C. At 20 min, 40 min, and 2.5 h time points, a solution of tert-butyl allyl{[allyl(2-oxoethy)amino]sulfonyl}carbamate (0.040 g, 0.125 mmol, 0.25 equiv.) in THF (0.20 mL) was added drop-wise at 0-5° C. At 2.5 h, a solution of sodium triacetoxyborohydride (0.211 g, 1.0 mmol, 0.2 equiv.) in trifluoroacetic acid (TFA, 1.5 mL, 9.5 mmol) was added at 0-5° C. The reaction was warmed to room temperature and stirred overnight. The reaction mixture was then poured into an ice-cold saturated solution of sodium carbonate (50 mL) and extracted with dichloromethane (3×20 mL). The combined dichloromethane extracts were washed with brine, dried over sodium sulfate, and concentrated. The residue was then purified on silica gel (0-75% ethyl acetate/hexane gradient elution) to give the desired product (0.239 g, 74.2%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.07 (m, 1H), 7.71 (m, 1H), 7.58 (t, 1H, J=8.7 Hz), 6.62 (m, 1H), 5.77 (m, 2H), 5.19 (m, 4H), 4.17 (m, 2H), 3.89 (m, 2H), 3.44 (m, 2H), 3.38 (m, 2H), 1.42 (s, 9H); C23H27BrFN7O7S (MW 644.47), LCMS (EI) m/e 544/546 (M+-Boc+H).

Provenance & Evidence