Ethyl Acetate → 2-Bromo-5-cyano-4-(cyclopropanecarbonylamino)-6-methylbiphenyl-3-yl cyclopropanecarboxylate

HRID 17304

反応式

HRID 17304 の反応式
[NH2:1][C:2]1[C:7]([OH:8])=[C:6]([Br:9])[C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:4]([CH3:16])[C:3]=1[C:17]#[N:18].C(N([CH:25]([CH3:27])[CH3:26])CC)(C)C.[CH:28]1([C:31](Cl)=[O:32])[CH2:30][CH2:29]1.[C:34](OCC)(=[O:36])C>>[CH:28]1([C:31]([O:8][C:7]2[C:6]([Br:9])=[C:5]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:4]([CH3:16])=[C:3]([C:17]#[N:18])[C:2]=2[NH:1][C:34]([CH:25]2[CH2:27][CH2:26]2)=[O:36])=[O:32])[CH2:30][CH2:29]1

参加物

5

反応物 4

HCID 8857Ethyl Acetate2 回HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 860974494-Amino-6-bromo-5-hydroxy-2-methylbiphenyl-3-carbonitrile

生成物 1

HCID 866308142-Bromo-5-cyano-4-(cyclopropanecarbonylamino)-6-methylbiphenyl-3-yl cyclopropanecarboxylate

実験手順

Under nitrogen atmosphere, 4-amino-6-bromo-5-hydroxy-2-methylbiphenyl-3-carbonitrile (I-42) (150 mg, 0.495 mmol) was dissolved in ethyl acetate (6 ml), diisopropylethylamine (431 μl, 2.48 mmol) was added, followed by cooling in an ice-water bath. Cyclopropanecarbonyl chloride (112 μl, 1.24 mmol) was dropwise added to it, followed by stirring overnight with restoring to room temperature. The reaction liquid was diluted with ethyl acetate, washed with saturated brine, then dried over anhydrous magnesium sulfate, concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1) to obtain 2-bromo-5-cyano-4-(cyclopropanecarbonylamino)-6-methylbiphenyl-3-yl cyclopropanecarboxylate (87 mg) and a mixture of (2-bromo-5-cyano-3-hydroxy-6-methylbiphenyl-4-yl)cyclopropanecarboxamide and 4-amino-2-bromo-5-cyano-6-methylbiphenyl-4-yl cyclopropanecarboxylate (110 mg). Subsequently, 2-bromo-5-cyano-4-(cyclopropanecarbonylamino)-6-methylbiphenyl-3-yl cyclopropanecarboxylate was dissolved in ethanol (30 ml), aqueous 0.1 N sodium hydroxide solution (5.94 ml) was added, followed by stirring overnight at room temperature. Ethanol was evaporated away under reduced pressure, then the residue was dissolved in ethyl acetate, followed by successively washing with 1 N hydrochloric acid, saturated brine, dried on anhydrous magnesium sulfate, concentrated under reduced pressure to obtain (2-bromo-5-cyano-3-hydroxy-6-methylbiphenyl-4-yl)cyclopropanecarboxamide (56 mg) as a colorless oil.

後処理

  1. temperatureby cooling in an ice-water bath
  2. customwith restoring to room temperature
  3. customThe reaction liquid
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1)

出典と根拠

ORDレコード
ord-93751ed956084696879bb3d9a03acb93
出典データセット
uspto-grants-2010_06
特許番号
US07737166B2

関連ノート

読み込み中…