Dimethyl Sulfone → 1-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-methanesulfonyl-ethanol

HRID 32020

反応式

HRID 32020 の反応式
[CH3:1][S:2]([CH3:5])(=[O:4])=[O:3].[Li]CCCC.CN(P(N(C)C)(N(C)C)=O)C.[Br:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]2[C:31]([CH:40]=[O:41])=[CH:32][C:33]3[NH:37][CH:36]=[N:35][C:34]=3[C:38]=2[F:39])=[C:25]([Cl:42])[CH:24]=1>C1COCC1>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]2[C:31]([CH:40]([OH:41])[CH2:1][S:2]([CH3:5])(=[O:4])=[O:3])=[CH:32][C:33]3[NH:37][CH:36]=[N:35][C:34]=3[C:38]=2[F:39])=[C:25]([Cl:42])[CH:24]=1

参加物

6

反応物 4

HCID 6213Dimethyl SulfoneHCID 12679HexamethylphosphoramideHCID 112456086-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehydeHCID 178418339Butyllithium

生成物 1

HCID 211141681-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-methanesulfonyl-ethanol収率 97.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of methyl sulfone (65 mg, 0.68 mmol) in THF (1.5 mL) is added a solution of n-BuLi (0.27 mL, 0.68 mmol, 2.5 M solution in hexane) at −78° C. After stirring for 5 minutes, HMPA (0.1 mL) is added. After stirring for additional 10 minutes, a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f (26 mg, 0.069 mmol) in THF (1 mL) is added. The resulting solution is stirred for 1.5 hours at −78° C. The reaction is quenched with saturated aqueous NH4Cl, warmed to room temperature, and diluted with EtOAc. The organic layer is washed with water, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (3% MeOH in CH2Cl2) to give the crude desired product (31 mg, 96%) which is used directly without further purification: MS APCI (+) m/z 462, 464 (M+, Br pattern) detected.

後処理

  1. stirringAfter stirring for additional 10 minutes
  2. stirringThe resulting solution is stirred for 1.5 hours at −78° C
  3. customThe reaction is quenched with saturated aqueous NH4Cl
  4. additiondiluted with EtOAc
  5. washThe organic layer is washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography (3% MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-339d876b24a643c6b06b5a50bc710c57
出典データセット
uspto-grants-2008_09
特許番号
US07425637B2

関連ノート

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