反应详情

温度

80 °C

A solution of 4-propyl-5-(pyridin-2-yl)isoxazole-3-carboxylic acid, sodium salt (13.5 mg, approx 0.053 mmol), HOBt (16.0 mg, 0.105 mmol), and diisopropylethylamine (0.041 mL, 0.233 mmol) in acetonitrile (1 mL) was added EDC (26.1 mg, 0.136 mmol) and tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate, Int. 1 (17.8 mg, 0.058 mmol). The reaction mixture was stirred at 80° C. for 2 h, cooled to room temperature, and concentrated to yield the crude product. The residue was dissolved in ethyl acetate (3 mL), washed with a saturated aqueous solution of sodium bicarbonate (1 mL), washed with water (1 mL), washed with brine (1 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification by preparative HPLC afforded tert-butyl 1-(4-(5-(4-propyl-5-(pyridin-2-yl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate. [Prep HPLC: Column: PHENOMENEX® S10 30×100 mm; Gradient time: 10 min; Flow rate=40 ml/min; Solvent A=10% MeOH—90% Water—0.1% TFA; Solvent B=90% MeOH—10% water—0.1% TFA; Start % B=20; Final % B=100.]

1. temperaturecooled to room temperature
2. concentrationconcentrated
3. customto yield the crude product
4. washwashed with a saturated aqueous solution of sodium bicarbonate (1 mL)
5. washwashed with water (1 mL)
6. washwashed with brine (1 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationConcentration
9. customfollowed by purification by preparative HPLC