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

HRID 1876042Notes

Reaction equation

HRID 1876042 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[CH3:9][C:10]1[N:11]=[CH:12][NH:13][CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:8][C:6]1[CH:7]=[C:2]([N:13]2[CH:14]=[C:10]([CH3:9])[N:11]=[CH:12]2)[N:3]=[CH:4][N:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 709434,6-DichloropyrimidineHCID 178418800HCID 178418800, compound

Product 1

HCID 263698384-Chloro-6-(4-methyl-1H-imidazol-1-yl)pyrimidineYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4,6-dichloropyrimidine (11.92 g, 80 mmol), 4-methyl-1H-imidazole (6.57 g, 80 mmol), and cesium carbonate (26.1 g, 80 mmol) was stirred in DMF (50 mL) at room temperature for 18 h. The reaction was diluted into 200 mL water and extracted three times with 200 mL EtOAc. The combined organic layers were concentrated and purified by flash chromatography on a 300 g silica gel cartridge with 25 to 75% ethyl acetate in hexane to yield a mixture of the two regioisomeric products. The pooled fractions were concentrated to about 200 mL volume and cooled to yield 4-chloro-6-(4-methyl-1H-imidazol-1-yl)pyrimidine (5.70 g, 37% yield). The positive identification of the 4-methylimidazole regioisomer was accomplished by its NMR NOE properties. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.80 (1H, d, J=0.50 Hz), 8.36 (1H, d, J=1.26 Hz), 7.29-7.31 (1H, m), 7.25 (1H, d, J=1.01 Hz), 2.27 (3H, d, J=1.01 Hz). LCMS: RT=0.50 min, MH+=195.1.

Workup

  1. extractionextracted three times with 200 mL EtOAc
  2. concentrationThe combined organic layers were concentrated
  3. custompurified by flash chromatography on a 300 g silica gel cartridge with 25 to 75% ethyl acetate in hexane
  4. customto yield
  5. additiona mixture of the two regioisomeric products
  6. concentrationThe pooled fractions were concentrated to about 200 mL volume
  7. temperaturecooled

Sources & evidence

ORD record
ord-2c83a0a237e04f15ad20ebedda799425
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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