Imidazole → 6-(1H-imidazol-1-yl)-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2364006Notes

Reaction equation

HRID 2364006 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH3:13])([CH3:12])[N:5]([CH3:14])[C:4]=2[CH:3]=1.[NH:15]1[CH:19]=[CH:18][N:17]=[CH:16]1.O.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu].[Cu]I.CN(C=O)C>[N:15]1([C:2]2[S:10][C:9]3[C:8](=[O:11])[NH:7][C:6]([CH3:13])([CH3:12])[N:5]([CH3:14])[C:4]=3[CH:3]=2)[CH:19]=[CH:18][N:17]=[CH:16]1

Participants

8

Reactant 4

HCID 795Imidazole2×HCID 962WaterHCID 10796Cesium carbonateHCID 667439846-bromo-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 667438606-(1H-imidazol-1-yl)-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 42.7%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 6-bromo-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (138 mg, 0.50 mmol), imidazole (68.1 mg, 1.00 mmol), copper (powder) (6.35 mg, 0.10 mmol) and water (2 mL) was refluxed for 1 h. The mixture was concentrated under reduced pressure. DMF (2 mL), cesium carbonate (326 mg, 1.00 mmol), imidazole (408 mg, 6.00 mmol) and copper(I) iodide (19.1 mg, 0.10 mmol) were added to the residue, and the mixture was purged with argon. Then, the mixture was stirred at 140° C. for 4 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc/THF (2:1, 100 mL×2), and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residual oil was purified by column chromatography (silica gel, EtOAc to 80:20 EtOAc/MeOH) to give a solid (56 mg). The solid was triturated with EtOAc/hexane, collected by filtration and washed with water to afford the title compound (10.4 mg, 7.9%) as a pale yellow solid:

Workup

  1. temperaturewas refluxed for 1 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe mixture was purged with argon
  4. additionThen, the mixture was poured into saturated aqueous NaHCO3 (100 mL)
  5. extractionextracted with EtOAc/THF (2:1, 100 mL×2)
  6. dry with materialthe extract was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residual oil was purified by column chromatography (silica gel, EtOAc to 80:20 EtOAc/MeOH)

Sources & evidence

ORD record
ord-9ec8bfbc02244f3fb3a57128b7a6ab86
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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