Benzyl Bromide → HCID 59252434, compound

HRID 42295Notes

Reaction equation

HRID 42295 reaction equation
[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([CH:18]4[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]4)[NH:16][CH:17]=3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:30](Br)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C)C=O.O>[CH2:30]([N:20]1[CH2:21][CH2:22][CH2:23][CH:18]([C:15]2[NH:14][C:13]([C:10]3[CH:11]=[N:12][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:8][CH:9]=3)=[CH:17][N:16]=2)[CH2:19]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 178420146HCID 178420146, compound

Product 1

HCID 59252434HCID 59252434, compoundYield 38.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution consisting of (±)-2-phenyl-5-(2-(piperidin-3-yl)-1H-imidazol-4-yl)pyrimidine (Example 22, 40 mg, 0.13 mmol) in dimethylformamide (2 mL) was added cesium carbonate (85 mg, 0.26 mmol) followed by benzyl bromide (27 mg, 0.16 mmol). The reaction mixture was stirred at room temperature for one hour and diluted with water and the organic material was extracted twice with ethyl acetate. The combined organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in dichloromethane/ethyl acetate and chromatographed on silica (4 g) eluted with 1:9 v/v ethanol-ethyl acetate. The purified material was diluted with toluene and concentrated. Solidification of the product was promoted with scratching under dichloromethane and hexane to afford the title compound (20 mg) as a colorless solid; melting point 179° C.; Rf 0.19 with 1:9 v/v ethanol-ethyl acetate; 1H-NMR (400 MHz; DMSO-d6) δ 12.1 (s, 1H), 9.18 (s, 2H), 8.2-8.4 (m, 2H), 7.8 (s, 1H), 7.4-7.6 (m, 4H), 7.22-7.35 (m, 4H), 7.18-7.22 (m, 4H), 3.4-3.6 (m, 2H), 2.9-3.0 (m, 2H), 2.7-2.9 (m, 1H), 2.02-2.1 (M, 1H), 1.9-2.1 (m, 2H), 1.62-1.8 (m, 1H), 1.5-1.62 (m, 2H); MS (ESI+) m/z 396 (M+1); H-PGDS FPBA IC50: 0.6 μM.

Workup

  1. extractionthe organic material was extracted twice with ethyl acetate
  2. dry with materialThe combined organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloromethane/ethyl acetate
  6. customchromatographed on silica (4 g)
  7. washeluted with 1:9 v/v ethanol-ethyl acetate
  8. additionThe purified material was diluted with toluene
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-a72eadd449d24807b8d4a51cf4779808
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Reaction notes

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