Triphosgene → HCID 178452689, compound

Participants

Reaction Steps

3-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-{3-[5-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-ureido}-propionic acid ethyl ester. To a solution of bis(trichloromethyl)carbonate (189 mg, 0.66 mmol) in dichloromethane (12 mL) and saturated aqueous NaHCO3 (0.8 mL) was slowly added a solution of tert-butyl 4-(3-(4-(2-(ethoxycarbonyl)-2-aminoethyl)-2-fluorophenyl)-1,2,4-oxadiazol-5-yl)phenylcarbamate (300 mg, 0.66 mmol) in dichloromethane (12 mL) at 0° C. The reaction mixture was then stirred at room temperature for 1 hr. TLC showed the reaction was completed. Saturated aqueous NaHCO3 (18 mL), pyridine (0.3 mL), and 3-(4-fluorophenyl)-1H-pyrazol-5-amine (177 mg, 1 mmol) were added to the reaction mixture. The resulting mixture was then stirred overnight. TLC showed the reaction was completed. The layers were separated and the aqueous portion was extracted with dichloromethane (2×50 mL). The combined organic layers were washed sequentially with aq. HCl solution (1N, 2×50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give the title compound (343 mg, 51% yield) as a yellow solid.

Provenance & Evidence