Pyridine → Tert-butyl-1-(4-(5-(5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Participants

Reaction Steps

To a solution of 5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazole-3-carbonyl fluoride (48 mg, 0.185 mmol) and tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate, Int. 1 (56.3 mg, 0.185 mmol) in dichloromethane (2 mL) was added pyridine (37.3 μL, 0.461 mmol). The reaction mixture was stirred at room temperature for 16 hrs. The reaction mixture was then concentrated under reduced pressure, and the residue was diluted with ethyl acetate (3 mL), washed with water (1 mL), washed with a saturated aqueous solution of sodium bicarbonate (1 mL), washed with brine (1 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure resulted in the crude mixture which was dissolved in acetonitrile (2 mL). A 1.0M solution of tetrabutylammonium fluoride in tetrahydrofuran (369 μL, 0.369 mmol) was added, and the solution was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (30 mL), washed with water (10 mL), washed with a saturated aqueous solution of sodium bicarbonate (10 mL), washed with brine (10 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by preparative HPLC afforded tert-butyl-1-(4-(5-(5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate, which was used in the next step without any further purification. The product had an HPLC retention time=2.97 min.—Column: YMC S5 COMBISCREEN® 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=528.3.

Provenance & Evidence