4-Fluoro-2-methylphenyl isothiocyanate → 2-[4-cyano-2-(4-fluoro-2-methyl-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester

HRID 562429ノート

反応式

HRID 562429 の反応式
[CH2:1]([O:3][C:4](=[O:21])[C:5]([C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([NH:17][CH3:18])[C:11]=1[C:19]#[N:20])([CH3:9])[C:6](=[O:8])[CH3:7])[CH3:2].[F:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=S)=[C:25]([CH3:32])[CH:24]=1>C1COCC1>[CH2:1]([O:3][C:4](=[O:21])[C:5]([C:10]1[CH:15]=[CH:14][C:13]2[N:16]=[C:30]([NH:29][C:26]3[CH:27]=[CH:28][C:23]([F:22])=[CH:24][C:25]=3[CH3:32])[N:17]([CH3:18])[C:12]=2[C:11]=1[C:19]#[N:20])([CH3:9])[C:6](=[O:8])[CH3:7])[CH3:2]

参加物

4

反応物 2

HCID 27373994-Fluoro-2-methylphenyl isothiocyanateHCID 110661612-(4-Amino-2-cyano-3-methylamino-phenyl)-2-methyl-3-oxo-butyric acid ethyl ester

生成物 1

HCID 668323242-[4-cyano-2-(4-fluoro-2-methyl-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester収率 56.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a glass scintillation vial was added 2-(4-amino-2-cyano-3-methylamino-phenyl)-2-methyl-3-oxo-butyric acid ethyl ester (0.247 g, 0.854 mmol), followed by THF (5 mL) and a magnetic stir bar. To the resulting solution was added 4-fluoro-1-isothiocyanato-2-methyl-benzene (0.191 g, 1.14 mmol) and the solution was stirred at room temperature for 48 h. To the solution was then added mercuric oxide (0.222 g, 1.02 mmol), and stirring was continued at room temperature for 24 h. The brown suspension was then filtered through a ½ inch thick pad of silica, washed with THF, and concentrated to dryness. The resulting deep red solid was further purified by silica gel chromatography, eluting with ethyl acetate:hexane (0%-100%) to provide 2-[4-cyano-2-(4-fluoro-2-methyl-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester (0.204 g, 56%) as a deep red solid. ESMS (m/z): (M+1)+ found, 423.

後処理

  1. waitwas continued at room temperature for 24 h
  2. filtrationThe brown suspension was then filtered through a ½ inch thick pad of silica
  3. washwashed with THF
  4. concentrationconcentrated to dryness
  5. customThe resulting deep red solid was further purified by silica gel chromatography
  6. washeluting with ethyl acetate

出典と根拠

ORDレコード
ord-8f33acbbcd504bb0b02e4c95041bd73e
出典データセット
uspto-grants-2011_11
特許番号
US08067395B2

反応ノート

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