Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 4-(4-{3-[2-(4-Fluorophenyl)acetyl]thioureido}phenoxy)-2-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyridine

HRID 492891노트

반응식

HRID 492891 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]=[C:12]=[S:13])=[O:10])=[CH:4][CH:3]=1.[NH2:14][C:15]1[CH:43]=[CH:42][C:18]([O:19][C:20]2[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]([N:29]3[CH2:34][CH2:33][CH:32]([N:35]4[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]4)[CH2:31][CH2:30]3)=[O:28])[CH:21]=2)=[CH:17][CH:16]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1.C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:11][C:12](=[S:13])[NH:14][C:15]2[CH:16]=[CH:17][C:18]([O:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]([N:29]4[CH2:30][CH2:31][CH:32]([N:35]5[CH2:36][CH2:37][N:38]([CH3:41])[CH2:39][CH2:40]5)[CH2:33][CH2:34]4)=[O:28])[CH:21]=3)=[CH:42][CH:43]=2)=[O:10])=[CH:6][CH:7]=1

참가 물질

6

반응물 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 231533634-(4-Aminophenoxy)-2-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyridine

생성물 1

HCID 576774754-(4-{3-[2-(4-Fluorophenyl)acetyl]thioureido}phenoxy)-2-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyridine수율 40%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 1140Toluene용매

실험 절차

After adding a solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.25 M, 3.0 ml) to a solution of 4-(4-aminophenoxy)-2-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyridine (149 mg) and (+)-10-camphorsulfonic acid (152 mg) in ethanol (4.0 ml) at room temperature, the mixture was stirred for 3 hours. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate. The organic layer was washed with saturated aqueous sodium hydrogencarbonate and brine and dried over anhydrous sodium sulfate. The solvent was then distilled off, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=98:2 to 97:3) to provide the title compound (88.2 mg, 40%) as white powder.

후처리

  1. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was then distilled off
  5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=98:2 to 97:3)

출처 및 근거

ORD 기록
ord-e259000839ce4fd989f5c86801d7d945
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07531532B2

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