1-Bromo-3,5-bis(trifluoromethyl)benzene → 4-(3,5-Bis(trifluoromethyl)phenyl)-6-propylpyrimidine-2-carbonitrile

HRID 733169Notes

Reaction equation

HRID 733169 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].[F:16][C:17]([F:30])([F:29])[C:18]1[CH:19]=[C:20](Br)[CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1>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>[F:16][C:17]([F:30])([F:29])[C:18]1[CH:19]=[C:20]([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:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1

Participants

5

Reactant 2

HCID 676021-Bromo-3,5-bis(trifluoromethyl)benzeneHCID 690493004-Propyl-6-trimethylstannanyl-pyrimidine-2-carbonitrile

Product 1

HCID 498624214-(3,5-Bis(trifluoromethyl)phenyl)-6-propylpyrimidine-2-carbonitrileYield 35.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

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 (155 mg, 0.50 mmol) and 3,5-bis-trifluoromethyl-bromobenzene (0.10 mL, 0.58 mmol) in dimethylformamide (3 mL). The mixture was refluxed for 4 hours 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: DCM) to afford a solid which was triturated in pentane. After filtration, 4-(3,5-bis-trifluoromethyl-phenyl)-6-propyl-pyrimidine-2-carbonitrile (63 mg, 35%) was obtained as an off white solid (mp=112° C.).

Workup

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

Sources & evidence

ORD record
ord-325d58f3933544e78d8062c1a27aa91d
Source dataset
uspto-grants-2009_09
Patent number
US07589095B2

Reaction notes

Loading…