1,2-Dimethoxyethane → 2-(2-chlorophenyl)-6-(5-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4(3H)-one

HRID 1022898Notes

Reaction equation

HRID 1022898 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[Cl:18])=[N:5][C:4]=2[CH:3]=1.[CH3:19][C:20]1[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][N:22](C(OC(C)(C)C)=O)[N:21]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:6]1[NH:7][C:8](=[O:11])[C:9]2[S:10][C:2]([C:24]3[CH:23]=[N:22][NH:21][C:20]=3[CH3:19])=[CH:3][C:4]=2[N:5]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 53216815Tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrazole-1-carboxylateHCID 1363339036-bromo-2-(2-chlorophenyl)thieno[3,2-d]pyrimidin-4(3H)-one

Product 1

HCID 1363339042-(2-chlorophenyl)-6-(5-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4(3H)-oneYield 27.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

6-Bromo-2-(2-chlorophenyl)thieno[3.2-d]pyrimidin-4(3H)-one (157 mg), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (425 mg), sodium carbonate (138 mg), 1,2-dimethoxyethane (4.0 mL) and water (2.0 mL) were placed in a flask, and the atmosphere in the flask was purged with argon. [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1) (38 mg) was added, and the atmosphere in the flask was purged again with argon. The reaction system was stirred at 100° C. for 1 hr, 8M aqueous sodium hydroxide solution (1 mL) was added, and the mixture was stirred at 100° C. for 30 min. After stirring, the mixture was extracted with ethyl acetate/tetrahydrofuran mixture, and the extract was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained pale-yellow solid was crystallized from methanol/ethyl acetate to give the title compound (43 mg) as a yellow solid.

Workup

  1. customthe atmosphere in the flask was purged with argon
  2. addition[1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1) (38 mg) was added
  3. customthe atmosphere in the flask was purged again with argon
  4. addition8M aqueous sodium hydroxide solution (1 mL) was added
  5. stirringthe mixture was stirred at 100° C. for 30 min
  6. stirringAfter stirring
  7. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran mixture
  8. concentrationthe extract was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  10. customthe obtained pale-yellow solid was crystallized from methanol/ethyl acetate

Sources & evidence

ORD record
ord-fb8dfb4495cd4da4aba56a3e1163e554
Source dataset
uspto-grants-2014_05
Patent number
US08722660B2

Reaction notes

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