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

HRID 2201243Notes

Reaction equation

HRID 2201243 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[NH:9][CH:10]=[C:11]3[C:16]=2[C:15](=[O:17])[N:14]([CH3:18])[C:13](=[O:19])[N:12]3[CH3:20])[CH:5]=[CH:6][CH:7]=1.CC(C)([O-])C.[K+].C1OCCOCCOCCOCCOCCOC1.FC(F)(F)S(O[CH2:51][CH:52]1[CH2:56][C:55](=[O:57])[O:54][CH2:53]1)(=O)=O>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH2:51][CH:52]3[CH2:56][C:55](=[O:57])[O:54][CH2:53]3)[CH:10]=[C:11]3[C:16]=2[C:15](=[O:17])[N:14]([CH3:18])[C:13](=[O:19])[N:12]3[CH3:20])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 2855718-Crown-6HCID 23665647Potassium tert-butoxideHCID 867229305-(3-fluorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dioneHCID 86723477(5-Oxotetrahydrofuran-3-yl)methyl trifluoromethanesulfonate

Product 1

HCID 867234785-(3-fluorophenyl)-1,3-dimethyl-6-((5-oxotetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-ab0ad7bad25c42739279f1164592849a
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

Loading…