Triethylamine → Tert-butyl 1-(4-(5-(3-phenyl-4-(2,2,2-trifluoroethylcarbamoyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Participants

Reaction Steps

A mixture of 5-(3-(4-((3-(tert-butoxycarbonyl)azetidin-1-yl)methyl)phenyl)-1,2,4-oxadiazol-5-yl)-3-phenylisoxazole-4-carboxylic acid (30 mg, 0.060 mmol), 2,2,2-trifluoroethylamine (7.15 μL, 0.090 mmol), BOP-Cl (18.24 mg, 0.072 mmol) and Et3N (0.025 mL, 0.179 mmol) in DMF (0.5 mL) was stirred at rt over the weekend. The reaction mixture was partitioned between EtOAc (30 mL) and saturated sodium bicarbonate solution (30 mL). The organic layer was washed with water (2×30 mL) and brine (30 mL). After drying (MgSO4) and filtration, the organic layer was concentrated to a colorless solid that was chromatographed on a 4 gm Isco silica gel cartridge, eluting with a 0-70% EtOAc/Hex gradient. The essentially pure fractions containing product were concentrated to afford tert-butyl 1-(4-(5-(3-phenyl-4-(2,2,2-trifluoroethylcarbamoyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (18 mg, 0.031 mmol, 51.7% yield) as a white solid. This material was deemed suitable to use in the next step without further purification. HPLC retention time=1.71 minutes (YMC Combi 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1 TFA a 2 minute gradient. MS: (M+H)=584.10.

Provenance & Evidence