1,2-Dimethoxyethane → 4-(2,2-dimethyl-4-oxo-1,2,3,4-tetrahydrothieno[3,2-d]pyrimidin-6-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-5-carbaldehyde

HRID 2364056Notes

Reaction equation

HRID 2364056 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH3:13])([CH3:12])[NH:5][C:4]=2[CH:3]=1.[CH:14]([C:16]1[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[N:19]=[CH:18][C:17]=1B(O)O)=[O:15].C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC>O>[CH3:12][C:6]1([CH3:13])[NH:5][C:4]2[CH:3]=[C:2]([C:17]3[CH:18]=[N:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:16]=3[CH:14]=[O:15])[S:10][C:9]=2[C:8](=[O:11])[NH:7]1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 667434256-bromo-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneHCID 86662300(5-formyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)boronic acid

Product 1

HCID 866623014-(2,2-dimethyl-4-oxo-1,2,3,4-tetrahydrothieno[3,2-d]pyrimidin-6-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-5-carbaldehydeYield 54.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 6-bromo-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (0.444 g, 1.70 mmol), (5-formyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)boronic acid (0.554 g, 2.05 mmol), cesium carbonate (2.77 g, 8.50 mmol), 1,2-dimethoxyethane (15 mL) and water (4 mL) was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (0.139 g, 0.17 mmol) was added, and the mixture was purged with argon again. The mixture was refluxed for 2 h. Then, the mixture was poured into water (100 mL) and EtOAc (100 mL). The insoluble materials were filtered off, and the organic layer was collected from the filtrate. This organic layer was washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residual oil was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc) to afford the title compound (374 mg, 54%) as a yellow solid:

Workup

  1. customwas purged with argon
  2. customthe mixture was purged with argon again
  3. temperatureThe mixture was refluxed for 2 h
  4. additionThen, the mixture was poured into water (100 mL) and EtOAc (100 mL)
  5. filtrationThe insoluble materials were filtered off
  6. customthe organic layer was collected from the filtrate
  7. washThis organic layer was washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residual oil was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc)

Sources & evidence

ORD record
ord-5fef08eec0be4f89987ef205002a49ef
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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