2-Chloropyridine → 3-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-5-(pyridin-2-yloxy)-1H-indole

HRID 1683929Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1683929
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]=1.[NH2:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][CH:29]=[C:28]2[CH:34]1[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]1.[C:47]([O:51][C:52]([N:54]1[CH2:59][CH2:58][C:57]([C:60]2[C:68]3[C:63](=[CH:64][CH:65]=[C:66]([OH:69])[CH:67]=3)[NH:62][CH:61]=2)=[CH:56][CH2:55]1)=[O:53])([CH3:50])([CH3:49])[CH3:48].Cl[C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][N:72]=1.C(=O)([O-])O.[Na+]>O1CCCC1.O1CCOCC1>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][C:11]([C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([NH:1][C:36]4[CH:35]=[CH:34][CH:39]=[CH:38][N:37]=4)[CH:3]=3)[NH:7][CH:6]=2)=[CH:12][CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21].[C:43]([O:42][C:40]([N:37]1[CH2:38][CH2:39][CH:34]([C:28]2[C:27]3[C:31](=[CH:32][CH:33]=[C:25]([NH:24][C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][N:54]=4)[CH:26]=3)[NH:30][CH:29]=2)[CH2:35][CH2:36]1)=[O:41])([CH3:46])([CH3:45])[CH3:44].[C:47]([O:51][C:52]([N:54]1[CH2:59][CH2:58][C:57]([C:60]2[C:68]3[C:63](=[CH:64][CH:65]=[C:66]([O:69][C:71]4[CH:76]=[CH:75][CH:74]=[CH:73][N:72]=4)[CH:67]=3)[NH:62][CH:61]=2)=[CH:56][CH2:55]1)=[O:53])([CH3:50])([CH3:48])[CH3:49]

Komponenten

10

Edukt 5

HCID 79772-ChloropyridineHCID 516892Sodium BicarbonateHCID 158394613-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-5-hydroxy-1H-indoleHCID 53986362tert-butyl 4-(5-amino-1H-indol-3-yl)piperidine-1-carboxylateHCID 543263845-amino-3-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-1H-indole

Produkt 3

HCID 190407253-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-5-(pyridin-2-yloxy)-1H-indoleHCID 190407463-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-5-(pyrid-2-ylamino)-1H-indoleHCID 190407603-(N-t-butoxycarbonylpiperid-4-yl)-5-(pyrid-2-ylamino)-1H-indole

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of 5-amino-3-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-1H-indole, 5-amino-3-(N-t-butoxycarbonylpiperid-4-yl)-1H-indole, or 3-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-5-hydroxy-1H-indole (10.0 mmol) and a base (12.0 mmol, 1.2 eq) in anhydrous tetrahydrofuran or dioxane (35 mL) was added the 2-chloropyridine (11.0 mmol, 1.1 eq). The resulting reaction solution was stirred at reflux or at room temperature under nitrogen for 3-48 hours, depending on substrate and reaction solvent. A saturated solution of sodium hydrogen carbonate (25 mL) was then added to the reaction mixture, and this aqueous mixture was extracted with ethyl acetate (3×25 mL). The organic extracts were combined, dried (Mg SO4), and evaporated under reduced pressure. The extraction residue was column chromatographed using silica gel (approximately 150 g) and elution with the appropriate solvent system to afford the desired 3-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-5-(pyrid-2-ylamino)-1H-indole, 3-(N-t-butoxycarbonylpiperid-4-yl)-5-(pyrid-2-ylamino)-1H-indole or 3-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-5-(pyridin-2-yloxy)-1H-indole.

Aufarbeitung

  1. customThe resulting reaction solution
  2. customdepending on substrate and reaction solvent
  3. extractionthis aqueous mixture was extracted with ethyl acetate (3×25 mL)
  4. dry with materialdried (Mg SO4)
  5. customevaporated under reduced pressure
  6. customchromatographed
  7. washsilica gel (approximately 150 g) and elution with the appropriate solvent system

Quellen und Nachweise

ORD-Eintrag
ord-f3e79bd8c22b4d3b848b337eb36962ef
Quelldatensatz
uspto-grants-1997_06
Patentnummer
US05639752

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