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 562429노트

반응식

HRID 562429 반응식
[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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8f33acbbcd504bb0b02e4c95041bd73e
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08067395B2

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