Imidazole → 4-Chloro-6-(1H-imidazol-1-yl)pyrimidine

HRID 1876039Notes

Reaction equation

HRID 1876039 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[NH:9]1[CH:13]=[CH:12][N:11]=[CH:10]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Cl:8][C:6]1[CH:7]=[C:2]([N:9]2[CH:13]=[CH:12][N:11]=[CH:10]2)[N:3]=[CH:4][N:5]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 11430Potassium CarbonateHCID 709434,6-Dichloropyrimidine

Product 1

HCID 27576124-Chloro-6-(1H-imidazol-1-yl)pyrimidineYield 63.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4,6-dichloropyrimidine (5.96 g, 40 mmol), imidazole (2.72 g, 40.0 mmol), and potassium carbonate (5.53 g, 40.0 mmol) was stirred in DMF (50 mL) at room temperature for 18 h. The reaction was diluted into 500 mL water and extracted five times with 150 mL EtOAc. The combined organic layers were concentrated and purified by flash chromatography on a 240 g silica gel cartridge with 0 to 10% methanol in ethyl acetate to yield 4-chloro-6-(1H-imidazol-1-yl)pyrimidine (4.56 g, 63% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.85 (1H, d, J=0.76 Hz), 8.45 (1H, s), 7.62 (1H, t, J=1.51 Hz), 7.34 (1H, d, J=0.76 Hz), 7.23 (1H, dd, J=1.38, 0.88 Hz). LCMS: RT=0.47 min, MH+=181.1.

Workup

  1. extractionextracted five times with 150 mL EtOAc
  2. concentrationThe combined organic layers were concentrated
  3. custompurified by flash chromatography on a 240 g silica gel cartridge with 0 to 10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-c86197c741854af48caeeb2c759308f6
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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