Reaction #8958

Reaction equation

methyliodide

Sodium hydride

2-methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)-pyridine

water

→

desired compound

4-(1,2-Dimethyl-1H-imidazol-4-ylethynyl)-2-methyl-pyridine

Solvents

THF

THF

THF

Conditions

Workup

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued overnight
3. 3
   Extractionextracted three times with ethyl acetate (70 mL each)
4. 4
   DryingThe combined organic extracts were dried with sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Otherevaporated
7. 7
   OtherThe crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient)
8. 8
   workup.ADDITIONa mixture of two regioisomers
9. 9
   Otherwas obtained
10. 10
    OtherThis mixture could be separated by HPLC (chiralpak AD, heptane/ethanol 4/1)

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+).

Source