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

HRID 1875719ノート

反応式

HRID 1875719 の反応式
[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

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 137636Cyclohexane, (bromomethyl)-HCID 717418032-(2-Chloropyridin-3-YL)-5,6-difluoro-1H-benzo[D]imidazole

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒3 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-ba6cce5a3fa74ab7b65fecc6175ea893
出典データセット
uspto-grants-2012_11
特許番号
US08309581B2

反応ノート

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