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

HRID 1683929Notes

Reaction equation

HRID 1683929 reaction equation
[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]

Participants

10

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-f3e79bd8c22b4d3b848b337eb36962ef
Source dataset
uspto-grants-1997_06
Patent number
US05639752

Reaction notes

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