Cesium carbonate → HCID 53379317, compound

HRID 869298Notes

Reaction equation

HRID 869298 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:21]1[N:26]=[C:25]([O:27]C)[C:24]([O:29]C)=[CH:23][N:22]=1>C1COCC1.[Pd]>[OH:29][C:24]1[C:25](=[O:27])[NH:26][C:21]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=2)=[N:22][CH:23]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 66569546HCID 66569546, compound

Product 1

HCID 53379317HCID 53379317, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

To a mixture of 0.05 g (0.26 mmol) 4-trifluoromethylphenylboronic acid, 0.02 g (0.009 mmol Pd EN Cat™ 30, and 0.65 mL 1 M aq Cs2CO3, was added a solution of 0.005 g (0.009 mmol) 1,1′-(bisdiphenylphosphino)ferrocene and 0.03 g (0.17 mmol) 2-chloro-4,5-dimethoxy-pyrimidine in 1 mL THF. The resulting mixture was heated by microwave to 150° C. for 10 minutes. After cooling, the aq layer was removed and the organic phase was filtered and concentrated. To the resulting residue was added 1 mL 33% HBr in AcOH, and the resulting mixture was heated by microwave to 160° C. for 5 min. The resulting solution was diluted with water (2 mL) and loaded onto an SCX column. After washing with MeOH (5 mL), the crude product was eluted off with 2 M ammonia in MeOH. Purification by automated mass-guided HPLC afforded 1.7 mg (4%) 5-hydroxy-2-(4-trifluoromethyl-phenyl)-3H-pyrimidin-4-one. NMR (499 MHz, DMSO-d6): δ 9.85 (br s, 1H); 8.22 (d, J=7.93 Hz, 2H); 7.85 (d, J=8.12 Hz, 2H); 7.63 (br s, 1H). High resolution mass spec (FT/ICR) calc (M+H)+=257.0533 found 257.0532.

Workup

  1. temperatureAfter cooling
  2. customthe aq layer was removed
  3. filtrationthe organic phase was filtered
  4. concentrationconcentrated
  5. additionTo the resulting residue was added 1 mL 33% HBr in AcOH
  6. temperaturethe resulting mixture was heated by microwave to 160° C. for 5 min
  7. additionThe resulting solution was diluted with water (2 mL)
  8. washAfter washing with MeOH (5 mL)
  9. washthe crude product was eluted off with 2 M ammonia in MeOH
  10. customPurification by automated mass-guided HPLC

Sources & evidence

ORD record
ord-688741a35cf54c20966c315b9b6910a1
Source dataset
uspto-grants-2015_03
Patent number
US08969364B2

Reaction notes

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