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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
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 520585
[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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Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 597024562-(Chloromethyl)-1,3-thiazole-4-carbonyl chloride3×HCID 670291711-(Phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-indazol-4-amine

Produkt 1

HCID 58356384
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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6212ChloroformLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-30620031f3bc46f1b2e2ac5d8774451b
Quelldatensatz
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09326987B2

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