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Diisopropylethylamine → 2-(Chloromethyl)-N-{1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-indazol-4-yl}-1,3-thiazole-4-carboxamide

HRID 520585
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HRID 520585 반응식
[C:1]1([S:7]([N:10]2[C:18]3[CH:17]=[C:16]([C:19]4[CH:24]=[CH:23][N:22]=[C:21]5[N:25]([S:28]([C:31]6[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=6)(=[O:30])=[O:29])[CH:26]=[CH:27][C:20]=45)[CH:15]=[C:14]([NH2:37])[C:13]=3[CH:12]=[N:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.[Cl:47][CH2:48][C:49]1[S:50][CH:51]=[C:52]([C:54](Cl)=[O:55])[N:53]=1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.C(Cl)Cl>[Cl:47][CH2:48][C:49]1[S:50][CH:51]=[C:52]([C:54]([NH:37][C:14]2[CH:15]=[C:16]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]4[N:25]([S:28]([C:31]5[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=5)(=[O:29])=[O:30])[CH:26]=[CH:27][C:20]=34)[CH:17]=[C:18]3[C:13]=2[CH:12]=[N:11][N:10]3[S:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)(=[O:9])=[O:8])=[O:55])[N:53]=1
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HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 597024562-(Chloromethyl)-1,3-thiazole-4-carbonyl chloride3회HCID 670291711-(Phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-indazol-4-amine

생성물 1

HCID 583563842-(Chloromethyl)-N-{1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-indazol-4-yl}-1,3-thiazole-4-carboxamide

시약·촉매·용매 2

HCID 6212Chloroform용매2회HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

1-(Phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-indazol-4-amine (663 mg) in chloroform (10 ml) was stirred at 0° C. DIPEA (0.437 ml) was added into the reaction mixture, then 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (300 mg) in chloroform (10 ml) was added. The reaction mixture was stirred at 0° C. for 15 min. 2-(Chloromethyl)-1,3-thiazole-4-carbonyl chloride (400 mg) was added to the reaction mixture and stirring was continued. 2-(Chloromethyl)-1,3-thiazole-4-carbonyl chloride (1.6 g) was added to the reaction mixture which was stirred under nitrogen for 18 h. The solution was treated with DCM (25 ml) and saturated sodium bicarbonate aq (25 ml), and then stirred for 10 min. The organic layer was separated, washed with diluted sodium chloride aq (25 ml) and then passed through a hydrophobic frit. A part of the solvent was removed then the solution was applied to a silica column (Flasmaster II, 100 g silica cartridge) and eluted with a gradient of 0-100% ethylacetate:cyclohexane over 60 min. Fractions containing desired product were combined and the solvent was removed to afford the title compound, 111 mg as a white solid.

후처리

  1. stirringstirring
  2. stirringwas stirred under nitrogen for 18 h
  3. stirringstirred for 10 min
  4. customThe organic layer was separated
  5. washwashed with diluted sodium chloride aq (25 ml)
  6. customA part of the solvent was removed
  7. washeluted with a gradient of 0-100% ethylacetate
  8. waitcyclohexane over 60 min
  9. additionFractions containing desired product
  10. customthe solvent was removed

출처 및 근거

ORD 기록
ord-30620031f3bc46f1b2e2ac5d8774451b
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09326987B2

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