Potassium Carbonate → 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 32002ノート

反応式

HRID 32002 の反応式
[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[Cl:22])=[C:12]([F:23])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH:30]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH2:31]>CN(C=O)C.C(OCC)(=O)C.O>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[Cl:22])=[C:12]([F:23])[C:8]2[N:9]=[CH:10][N:11]([CH2:31][CH2:30][S:32]([CH3:35])(=[O:34])=[O:33])[C:7]=2[CH:6]=1)=[O:4]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 19354Methyl vinyl sulfoneHCID 11749905Methyl 6-((4-bromo-2-chlorophenyl)amino)-7-fluoro-1H-benzo[d]imidazole-5-carboxylate

生成物 1

HCID 672515916-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester収率 59.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 8b (1.55 g, 3.89 mmol) is dissolved in 15 mL DMF under N2. K2CO3 (0.70 g, 5.06 mmol) is added followed by methyl vinyl sulfone (0.41 mL, 4.67 mmol). After stirring 16 hours at room temperature, the reaction mixture is diluted with ethyl acetate and water. The layers are separated and the organic layer is washed with water (3×) and brine. The combined aqueous washes are extracted with ethyl acetate. The combined organic extracts are dried (MgSO4) and concentrated under reduced. Purification by dissolving the residue in methylene chloride and precipitating with diethyl ether, repeated several times, provides 1.16 g (59%) pure desired product as a yellow solid: MS APCI (+) m/z 506, 504 (M+Br pattern) and 400, 398 (M−methyl ethyl sulfone Br pattern).

後処理

  1. customThe layers are separated
  2. washthe organic layer is washed with water (3×) and brine
  3. extractionThe combined aqueous washes are extracted with ethyl acetate
  4. dry with materialThe combined organic extracts are dried (MgSO4)
  5. concentrationconcentrated under reduced
  6. customPurification
  7. dissolutionby dissolving the residue in methylene chloride
  8. customprecipitating with diethyl ether

出典と根拠

ORDレコード
ord-18f95a6b2d6549c6972d445cd77b5792
出典データセット
uspto-grants-2008_09
特許番号
US07425637B2

反応ノート

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