Methyl iodide → 7-Chloro-2-(1-ethyl-1H-imidazol-4-yl)thieno[3,2-b]pyridine

HRID 2193698Notes

Reaction equation

HRID 2193698 reaction equation
[CH2:1]([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[N:17]=[CH:18][N:19]([CH2:21][CH3:22])[CH:20]=3)[S:15][C:8]=12.CI>O1CCCC1>[Cl:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[N:17]=[C:18]([CH3:1])[N:19]([CH2:21][CH3:22])[CH:20]=3)[S:15][C:8]=12.[Cl:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[N:17]=[CH:18][N:19]([CH2:21][CH3:22])[CH:20]=3)[S:15][C:8]=12

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 587901157-Chloro-2-(1-ethyl-1H-imidazol-4-yl)thieno[3,2-b]pyridineHCID 178418339Butyllithium

Product 2

HCID 587900327-Chloro-2-(1-ethyl-2-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridineHCID 587901157-Chloro-2-(1-ethyl-1H-imidazol-4-yl)thieno[3,2-b]pyridineYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-Butyllithium was added to a solution at −78° C. of 7-chloro-2-(1-ethyl-1H-imidazol-4-yl)thieno[3,2-b]pyridine (13, scheme 4) in tetrahydrofuran and stirred for about 15 minutes. Methyl iodide was added slowly and the reaction mixture was stirred at −78° C. until completion of the reaction. The mixture was quenched with water then allowed to warm to room temperature. The aqueous solution was extracted three times with ethyl acetate. The combined organic extracts were washed with water and brine, then dried over anhydrous MgSO4, filtered and evaporated. The crude product was purified by flash chromatography (eluent: 100% DCM to 2% MeOH/98% DCM) to afford the title compound 107 (as a mixture with about 15% of the starting material 13) as a yellow solid (190 mg, 80% yield). MS (m/z): 278.0 (M+H).

Workup

  1. stirringthe reaction mixture was stirred at −78° C. until completion of the reaction
  2. customThe mixture was quenched with water
  3. extractionThe aqueous solution was extracted three times with ethyl acetate
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by flash chromatography (eluent: 100% DCM to 2% MeOH/98% DCM)

Sources & evidence

ORD record
ord-98f9bb7ad6af4ed2a072f872beb9db37
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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