Benzyl Bromide → 5-(1-benzyl-1H-imidazol-4-yl)-2-phenylpyrimidine

HRID 2274491Notes

Reaction equation

HRID 2274491 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[N:8][C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:10][CH:11]=2)[N:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C)C=O.ClCCl>[CH2:24]([N:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[N:10][C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:8][CH:7]=2)[N:3]=[CH:2]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 178420150HCID 178420150, compound

Product 1

HCID 592524055-(1-benzyl-1H-imidazol-4-yl)-2-phenylpyrimidineYield 36.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution consisting of 5-(1H-imidazol-4-yl)-2-phenylpyrimidine (Step B, 0.050 g, 0.193 mmol) in N,N-dimethylformamide (10 mL) was added potassium carbonate (0.133 g, 0.965 mmol) at room temperature under dry conditions. After heating the reaction mixture in an 80° C. oil bath for one hour, benzyl bromide (Aldrich, 0.039 g, 0.231 mmol) was added to the mixture. The solution was left stirring in an 80° C. oil bath for 24 hours. Upon cooling, the reaction was diluted with dichloromethane (100 mL) and washed with saturated aqueous ammonium chloride (50 mL), water (50 mL) and brine (50 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was chromatographed on silica. Elution through an 8-g Silicycle® flash silica cartridge with gradient of 100% dichloromethane to 5% methanol in dichloromethane afforded the title compound as a white solid (22 mg, 36%). Rf 0.56 with 95:5 v/v dichloromethane-methanol; melting point 195° C.; 1H-NMR (400 MHz; DMSO-d6) δ 9.25 (s, 2H), 8.44-8.42 (m, 2H), 8.03 (s, 2H), 7.56-7.54 (m, 3H), 7.45-7.36 (m, 5H), 5.38 (s, 2H); MS (ESI+) m/z 313.1 (M+1); H-PGDS FPBA IC50: 4 μM.

Workup

  1. waitThe solution was left
  2. temperatureUpon cooling
  3. washwashed with saturated aqueous ammonium chloride (50 mL), water (50 mL) and brine (50 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica
  8. washElution through an 8-g Silicycle® flash silica cartridge with gradient of 100% dichloromethane to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-881396066e774fcbacb7d5207f121716
Source dataset
uspto-grants-2015_09
Patent number
US09126973B2

Reaction notes

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