Sodium hydride → 2-(2-chloro-pyridin-3-yl)-1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazole

HRID 1875719Notes

Reaction equation

HRID 1875719 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:9]([C:10]2[NH:14][C:13]3[CH:15]=[C:16]([F:20])[C:17]([F:19])=[CH:18][C:12]=3[N:11]=2)=[CH:8][CH:7]=[CH:6][N:5]=1.Br[CH2:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>CN(C)C=O>[Cl:3][C:4]1[C:9]([C:10]2[N:11]([CH2:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:12]3[CH:18]=[C:17]([F:19])[C:16]([F:20])=[CH:15][C:13]=3[N:14]=2)=[CH:8][CH:7]=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 137636Cyclohexane, (bromomethyl)-HCID 71741803HCID 71741803, compound

Product 1

HCID 866522862-(2-chloro-pyridin-3-yl)-1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazoleYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of sodium hydride (0.40 g, 60%, 10 mmol) in dry N,N-dimethylformamide (10 ml) at 25° C. was slowly added a solution of 2-(2-chloro-pyridin-3-yl)-5,6-difluoro-1H-benzoimidazole (1.33 g, 5 mmol) in dry N,N-dimethylformamide (5 ml), and was allowed to stir for 0.5 h. A solution of bromomethyl-cyclohexane (1.06 g, 6 mmol; CAS Reg. No. 2550-36-9) in N,N-dimethylformamide (5 ml) was then added drop wise to the above solution, and further stirred for 16 h at 25° C. The reaction mixture was quenched with saturated aqueous solution of ammonium chloride. The solvents were removed under reduced pressure. The crude material was dissolved in ethyl acetate, washed with water, and then with brine, dried over sodium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by column chromatography over silica gel (20% ethyl acetate/n-hexane) to afford the title compound as a colorless solid (51%). MS (Turbo Spray): m/z=362.2 (M+H).

Workup

  1. stirringfurther stirred for 16 h at 25° C
  2. customThe reaction mixture was quenched with saturated aqueous solution of ammonium chloride
  3. customThe solvents were removed under reduced pressure
  4. dissolutionThe crude material was dissolved in ethyl acetate
  5. washwashed with water
  6. dry with materialwith brine, dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by column chromatography over silica gel (20% ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-ba6cce5a3fa74ab7b65fecc6175ea893
Source dataset
uspto-grants-2012_11
Patent number
US08309581B2

Reaction notes

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