Water → 4-[(1,2-Dimethyl-1H-imidazol-4-yl)ethynyl]-2-methylpyridine

HRID 8862Notes

Reaction equation

HRID 8862 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:9]=[C:8]([C:10]#[C:11][C:12]2[N:13]=[C:14]([CH3:17])[NH:15][CH:16]=2)[CH:7]=[CH:6][N:5]=1.[CH3:18]I.O>C1COCC1>[CH3:18][N:15]1[CH:16]=[C:12]([C:11]#[C:10][C:8]2[CH:7]=[CH:6][N:5]=[C:4]([CH3:3])[CH:9]=2)[N:13]=[C:14]1[CH3:17]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178418884HCID 178418884, compound

Product 1

HCID 111485294-[(1,2-Dimethyl-1H-imidazol-4-yl)ethynyl]-2-methylpyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Sodium hydride (76 mg, 55%, 1.57 mmol) was suspended in 2 mL of dry THF. A solution of 2-methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)-pyridine (150 mg, 0.76 mmol) in 8 mL of dry THF was added and the reaction mixture was stirred at room temperature for 30 min. A solution of methyliodide (142 mg, 1.00 mmol) in 1 mL of dry THF was added and stirring was continued overnight. The reaction mixture was poured into 70 mL of water and extracted three times with ethyl acetate (70 mL each). The combined organic extracts were dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient) and a mixture of two regioisomers was obtained. This mixture could be separated by HPLC (chiralpak AD, heptane/ethanol 4/1) and the desired compound was obtained as a white solid (40 mg, 25%), MS: m/e=212.2 (M+H+).

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. extractionextracted three times with ethyl acetate (70 mL each)
  4. dry with materialThe combined organic extracts were dried with sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient)
  8. additiona mixture of two regioisomers
  9. customwas obtained
  10. customThis mixture could be separated by HPLC (chiralpak AD, heptane/ethanol 4/1)

Sources & evidence

ORD record
ord-05d081150e494ba1a9034aa8e3bd60ad
Source dataset
uspto-grants-2006_08
Patent number
US07091222B2

Reaction notes

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