1,2-Dimethoxyethane → 6-(3,5-dimethyl-1H-pyrazol-4-yl)-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2364011Notes

Reaction equation

HRID 2364011 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.[CH3:15][C:16]1[C:20](B2OC(C)(C)C(C)(C)O2)=[C:19]([CH3:30])[NH:18][N:17]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH3:15][C:16]1[C:20]([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)=[C:19]([CH3:30])[NH:18][N:17]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 162177133,5-Dimethylpyrazole-4-boronic acid, pinacol esterHCID 667439846-bromo-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 667441066-(3,5-dimethyl-1H-pyrazol-4-yl)-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 36%

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), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (333 mg, 1.50 mmol), sodium carbonate (265 mg, 2.50 mmol), 1,2-dimethoxyethane (5 mL) and water (2 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 EtOAc (100 mL), and the mixture was shaken well. The insoluble materials were filtered off. From the filtrate, the organic layer was collected, 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 EtOAc to 90:10 EtOAc/MeOH). The obtained yellow solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (52.2 mg, 36%) 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) and EtOAc (100 mL)
  5. filtrationThe insoluble materials were filtered off
  6. customFrom the filtrate, the organic layer was collected
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThis residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc
  12. customThe obtained yellow solid was triturated with EtOAc/hexane
  13. filtrationcollected by filtration

Sources & evidence

ORD record
ord-398c3bb3774f4cb5a8436303066a3fc2
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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