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

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Reaction Steps

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.

Provenance & Evidence