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

HRID 2364022Notes

Reaction equation

HRID 2364022 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.[N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18](B(O)O)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC>O>[CH3:14][N:5]1[C:4]2[CH:3]=[C:2]([C:18]3[C:19]4[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=4)[N:15]=[CH:16][CH:17]=3)[S:10][C:9]=2[C:8](=[O:11])[NH:7][C:6]1([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 2762748Quinoline-4-boronic acidHCID 667439846-bromo-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 667441091,2,2-trimethyl-6-quinolin-4-yl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 29.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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), quinolin-4-ylboronic acid (173 mg, 1.00 mmol), cesium carbonate (489 mg, 1.50 mmol), 1,2-dimethoxyethane (5 mL) and water (1 mL) was purged with argon. Then, 1,1′-bis(diphenylphosphino) ferrocenepalladium (II) dichloride dichloromethane adduct (40.8 mg, 0.050 mmol) was added, and the mixture was purged with argon again. This mixture was refluxed for 18 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (100 mL), and the extract was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. This residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH). The obtained yellow solid (62 mg) was triturated with EtOAc/hexane, and the precipitate was collected by filtration to afford the title compound (47.2 mg, 29%) as a pale yellow solid:

Workup

  1. customwas purged with argon
  2. customthe mixture was purged with argon again
  3. temperatureThis mixture was refluxed for 18 h
  4. additionThen, the mixture was poured into saturated aqueous NaHCO3 (100 mL)
  5. extractionextracted with EtOAc (100 mL)
  6. washthe extract was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThis residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc
  11. customThe obtained yellow solid (62 mg) was triturated with EtOAc/hexane
  12. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-41adc3bd870544849d3a25bdf2977261
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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