N-Iodosuccinimide → 7-(2-Chloro-4-iodophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one

HRID 1723686ノート

反応式

HRID 1723686 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[C:10]([F:21])=[C:11]([F:20])[CH:12]=[C:13]2[C:17]=1[C:16](=[O:18])[NH:15][CH:14]2[CH3:19].C1C(=O)N([I:29])C(=O)C1>C1COCC1.CO.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([I:29])[CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[C:10]([F:21])=[C:11]([F:20])[CH:12]=[C:13]2[C:17]=1[C:16](=[O:18])[NH:15][CH:14]2[CH3:19]

参加物

5

反応物 2

HCID 120273N-IodosuccinimideHCID 674048837-(2-Chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one

生成物 1

HCID 112819537-(2-Chloro-4-iodophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one収率 21.1%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 21899815MeOH tetrahydrofuran溶媒

実験手順

A solution of 7-(2-chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one (18 mg, 0.059 mmol), NIS (17 mg, 0.074 mmol), and p-TsOH-H2O (24 mg, 0.12 mmol) in THF-MeOH (1 mL/1 mL) was stirred for 1 hour at room temperature. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3 and water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to give the crude material that was purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2) to afford 7-(2-chloro-4-iodophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one (5.4 mg, 21%). MS APCI (−) m/z 433, 435 (M-, Cl pattern) detected; 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.70 (d, 1H), 7.48 (dd, 1H), 6.75 (m, 2H), 6.04 (s, 1H), 4.63 (q, 1H), 1.49 (d, 3H).

後処理

  1. washwashed with saturated aqueous NaHCO3 and water
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give the crude material that
  6. customwas purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-aad316fcf0b14f9087ca943204224856
出典データセット
uspto-grants-2009_02
特許番号
US07485643B2

反応ノート

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