反应详情

TSTU (220 mg, 0.68 mmol) was added in one portion to a stirred suspension of 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (250 mg, 0.57 mmol, >98% enantiomeric purity, see Example 1.06 for details of preparation), morpholine (0.075 mL, 0.86 mmol) and DIPEA (0.149 mL, 0.86 mmol) dissolved in DCM (5 mL) at room temperature under nitrogen. The resulting suspension was stirred at room temperature for 16 h. The reaction mixture was purified by preparative HPLC. The fractions were evaporated to dryness, the obtained foam was dissolved in DCM (0.5 mL) and diethyl ether (1 mL) was added. The resulting crystalline solid was collected by filtration and dried under vacuum to give 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one (126 mg, 44%) as a white crystalline solid.

1. customThe reaction mixture was purified by preparative HPLC
2. customThe fractions were evaporated to dryness
3. dissolutionthe obtained foam was dissolved in DCM (0.5 mL)
4. additiondiethyl ether (1 mL) was added
5. filtrationThe resulting crystalline solid was collected by filtration
6. customdried under vacuum