18-Crown-6 → 5-(3-fluorophenyl)-1,3-dimethyl-6-((5-oxotetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

5-(3-Fluorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (2.50 g, 9.2 mmol) was added portionwise to a mixture of potassium tert-butoxide (1.18 g, 10.5 mmol) and 18-crown-6 (242 mg, 0.92 mmol) in THF (15 mL), and stirred at room temperature for 15 minutes. A solution of (5-oxotetrahydrofuran-3-yl)methyl trifluoromethanesulfonate (2.61 g, 10.5 mmol) in THF (7.5 mL) was then added, maintaining the temperature at ˜20° C. using a water bath. The solution was stirred at room temperature for 1 hour. The reaction was quenched with saturated NH4Cl(aq) (10 mL), diluted with dichloromethane (100 mL) and washed with saturated NH4Cl(aq) (2×50 mL). The organic phase was dried over magnesium sulfate and the solvent evaporated under vacuum. Purification by chromatography on silica, eluting with 40-100% EtOAc/hexane, afforded the title compound.

1. temperaturemaintaining the temperature at ˜20° C.
2. stirringThe solution was stirred at room temperature for 1 hour
3. customThe reaction was quenched with saturated NH4Cl(aq) (10 mL)
4. additiondiluted with dichloromethane (100 mL)
5. washwashed with saturated NH4Cl(aq) (2×50 mL)
6. dry with materialThe organic phase was dried over magnesium sulfate
7. customthe solvent evaporated under vacuum
8. customPurification by chromatography on silica
9. washeluting with 40-100% EtOAc/hexane

ORDレコード

ord-ab0ad7bad25c42739279f1164592849a

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09359381B2