反应详情

HATU (368 mg, 0.97 mmol) was added to a stirred solution of 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (212 mg, 0.48 mmol >98% enantiomeric purity, see Example 1.06 for details of preparation) and DIPEA (0.674 mL, 3.87 mmol) dissolved in DCM (1 mL) under nitrogen. The resulting solution was stirred at room temperature for 1 h. Azetidine hydrochloride (271 mg, 2.90 mmol) was added and the mixture was stirred at room temperature for 15 h. The reaction mixture was purified by preparative HPLC. The fractions were evaporated to dryness to afford 6-(azetidine-1-carbonyl)-8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4H-chromen-4-one (28 mg, 12%) as a pale yellow foam.

1. stirringthe mixture was stirred at room temperature for 15 h
2. customThe reaction mixture was purified by preparative HPLC
3. customThe fractions were evaporated to dryness