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

HRID 2364021Notes

Reaction equation

HRID 2364021 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.CC1(C)C(C)(C)OB([C:23]2[CH:28]=[CH:27][N:26]=[C:25]3[NH:29][CH:30]=[CH:31][C:24]=23)O1.C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC>O>[CH3:14][N:5]1[C:4]2[CH:3]=[C:2]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]4[NH:29][CH:30]=[CH:31][C:24]=34)[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 497588714-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 667439846-bromo-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 667433861,2,2-trimethyl-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 30%

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), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (183 mg, 0.75 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 2:1 EtOAc/THF (100 mL×3), and the extract was 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 was triturated with EtOAc/hexane, and the precipitate was collected by filtration to afford the title compound (46.9 mg, 30%) 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 2:1 EtOAc/THF (100 mL×3)
  6. dry with materialthe extract was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThis residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc
  10. customThe obtained yellow solid was triturated with EtOAc/hexane
  11. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-b14ac37ca8394423a6724343379306fa
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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