Toluene → HCID 59351598, compound

HRID 1889425Notes

Reaction equation

HRID 1889425 reaction equation
Cl[C:2]1[NH:7][C:6](=[O:8])[NH:5][C:4](=[O:9])[CH:3]=1.Br[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][C:13]=1[F:26].[C:27](=[O:30])([O-])[O-].[K+].[K+].[OH-].[Na+].[C:35]1(C)C=CC=C[CH:36]=1>C(Cl)(Cl)Cl.CS(C)=O>[O:8]=[C:6]1[NH:5][C:4](=[O:9])[CH:3]=[C:2]([O:30][CH2:27][CH2:35][CH3:36])[N:7]1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][C:13]=1[F:26]

Participants

8

Reactant 5

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 732726-ChlorouracilHCID 574600744'-(Bromomethyl)-3'-fluorobiphenyl-2-carbonitrile

Product 1

HCID 59351598HCID 59351598, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6212ChloroformSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 6-chloropyrimidine-2,4(1H,3H)-dione (5 g), 4′-(bromomethyl)-3′-fluorobiphenyl-2-carbonitrile (9.9 g), potassium carbonate (2.36 g) and dimethyl sulfoxide (35 mL) was stirred at 65° C. for 2 hr. To the reaction mixture were added 1N aqueous sodium hydroxide solution (35 mL) and toluene (30 mL), and the mixture was cooled to 0° C. The precipitated solid was dissolved in chloroform, and the mixture was extracted with 1N hydrochloric acid. The obtained chloroform layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in n-propanol (60 mL), a solution of sodium (0.58 g) in n-propanol (30 mL) was added, and the mixture was stirred at 100° C. for 16 hr. The reaction mixture was concentrated under reduced pressure, and the obtained residue was extracted with 1N aqueous sodium hydroxide solution (50 mL) and ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC to give the title compound as a colorless solid (0.55 g, 26%).

Workup

  1. temperaturethe mixture was cooled to 0° C
  2. extractionthe mixture was extracted with 1N hydrochloric acid
  3. washThe obtained chloroform layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionThe obtained residue was dissolved in n-propanol (60 mL)
  7. additiona solution of sodium (0.58 g) in n-propanol (30 mL) was added
  8. stirringthe mixture was stirred at 100° C. for 16 hr
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. extractionthe obtained residue was extracted with 1N aqueous sodium hydroxide solution (50 mL) and ethyl acetate
  11. washThe ethyl acetate layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customThe obtained residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-2a5226acba434a0e87f722bfa859c51b
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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