Ammonium formate → 2-Phenyl-5-(2-phenyl-1H-imidazol-5-yl)pyrimidine

HRID 42278Notes

Reaction equation

HRID 42278 reaction equation
C([N:8]1[C:12]([C:13]2[CH:14]=[N:15][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:17][CH:18]=2)=[CH:11][N:10]=[C:9]1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[Pd]>[C:19]1([C:16]2[N:15]=[CH:14][C:13]([C:12]3[NH:8][C:9]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)=[N:10][CH:11]=3)=[CH:18][N:17]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 592524685-(1-benzyl-2-phenyl-1H-imidazol-5-yl)-2-phenylpyrimidine

Product 1

HCID 451374132-Phenyl-5-(2-phenyl-1H-imidazol-5-yl)pyrimidineYield 57.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution consisting of 5-(1-benzyl-2-phenyl-1H-imidazol-5-yl)-2-phenylpyrimidine (0.495 g, 1.27 mmol) in methanol (100 mL) was added ammonium formate (Aldrich, 0.804 g, 12.7 mmol) and 10% palladium on carbon (Alfa Aesar, 0.500 g). The reaction mixture was brought to reflux at 70° C. for 16 hours. After cooling the solution to room temperature, the crude reaction mixture was filtered over a bed of Celite, which was rinsed with additional methanol (300 mL). Concentration of the filtrate afforded an off-white solid. The product was purified by flash silica column chromatography. Elution through a 40-g Silicycle® flash silica cartridge with gradient of 100% dichloromethane to 5% methanol in dichloromethane afforded the title compound as a white solid (0.218 g, 57% yield); Rf 0.56 with 95:5 v/v dichloromethane-methanol; melting point 253° C.; 1H-NMR (400 MHz; DMSO-d6) δ 9.3 (s, 2H), 8.4 (m, 2H), 8.05 (m, 3H), 7.55-7.35 (m, 6H); MS (ESI+) m/z 299.1 (M+1); H-PGDS FPBA IC50: 0.25 μM; H-PGDS inhibitor EIA IC50: 0.012 μM.

Workup

  1. temperatureAfter cooling the solution to room temperature
  2. customthe crude reaction mixture
  3. filtrationwas filtered over a bed of Celite, which
  4. washwas rinsed with additional methanol (300 mL)
  5. customConcentration of the filtrate afforded an off-white solid
  6. customThe product was purified by flash silica column chromatography
  7. washElution through a 40-g Silicycle® flash silica cartridge with gradient of 100% dichloromethane to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-4443b9bc58644b52a1ea20a4d4990edc
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Reaction notes

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