4-Bromo-1-methoxy-2-(trifluoromethyl)benzene → 4-(4-Methoxy-3-(trifluoromethyl)phenyl)-6-propylpyrimidine-2-carbonitrile

HRID 733192Notes

Reaction equation

HRID 733192 reaction equation
[CH2:1]([C:4]1[CH:9]=[C:8]([Sn](C)(C)C)[N:7]=[C:6]([C:14]#[N:15])[N:5]=1)[CH2:2][CH3:3].[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21](Br)=[CH:20][C:19]=1[C:25]([F:28])([F:27])[F:26]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:8]2[CH:9]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]=[C:6]([C:14]#[N:15])[N:7]=2)=[CH:20][C:19]=1[C:25]([F:28])([F:27])[F:26]

Participants

5

Reactant 2

HCID 27753044-Bromo-1-methoxy-2-(trifluoromethyl)benzeneHCID 690493004-Propyl-6-trimethylstannanyl-pyrimidine-2-carbonitrile

Product 1

HCID 498624724-(4-Methoxy-3-(trifluoromethyl)phenyl)-6-propylpyrimidine-2-carbonitrileYield 11.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Bis(triphenylphosphine)palladium dichloride (34 mg, 0.05 mmol) was added under a nitrogen atmosphere to a mixture of 4-propyl-6-trimethylstannanyl-pyrimidine-2-carbonitrile (150 mg, 0.48 mmol) and 4-methoxy-3-trifluoromethyl-bromobenzene (148 mg, 0.58 mmol) in dimethylformamide (3 mL). The mixture was heated for 5 hours at 80° C. then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were concentrated under reduced pressure. The residue was chromatographed over silica gel (eluent Cyclohexane/DCM 7/3) to afford a solid which was triturated in pentane. After filtration, 4-(4-methoxy-3-trifluoromethyl-phenyl)-6-propyl-pyrimidine-2-carbonitrile (18 mg, 11%) was obtained as an off white solid.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. customThe residue was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted twice with ethyl acetate
  4. concentrationThe combined organic layers were concentrated under reduced pressure
  5. customThe residue was chromatographed over silica gel (eluent Cyclohexane/DCM 7/3)
  6. customto afford a solid which
  7. customwas triturated in pentane
  8. filtrationAfter filtration

Sources & evidence

ORD record
ord-a9d80b6fad584e33b7f31fdd07669c47
Source dataset
uspto-grants-2009_09
Patent number
US07589095B2

Reaction notes

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