反应详情

A solution of 5-fluoro-1,3-dihydro-indol-2-one (113 mg, 0.75 mmol.) in THF (1 mL) is placed under an argon atmosphere cooled in an ice bath. A solution of lithium bis(trimethylsilyl)amide (2 mL of a 1M solution in THF, 2 mmol) is added slowly at 0° C. and the resulting solution is stirred for 10 min. The ice-bath is removed and a solution of 2-morpholin-4-ylmethyl-7H-furo[3,4-b]pyridin-5-one (120 mg, 0.5 mmol) in THF (2 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 4 h and then poured into a 10% aqueous HCl solution. The resulting solution is stirred for 48 h at room temperature. The solid which precipitated from solution is collected by filtration and washed sequentially with small volumes of MeOH, EtOAc, Et2O (3×5 mL). The residual solid is purified by chromatography (silica gel, 5% MeOH in EtOAc). The product containing fractions are concentrated to give the title compound as a yellow solid (65 mg, 35%).

1. temperaturecooled in an ice bath
2. customThe ice-bath is removed
3. stirringThe resulting solution is stirred for 4 h
4. stirringThe resulting solution is stirred for 48 h at room temperature
5. customThe solid which precipitated from solution
6. filtrationis collected by filtration
7. washwashed sequentially with small volumes of MeOH, EtOAc, Et2O (3×5 mL)
8. customThe residual solid is purified by chromatography (silica gel, 5% MeOH in EtOAc)
9. additionThe product containing fractions
10. concentrationare concentrated