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. 2015 Jun 3;56(23):3413-3415.
doi: 10.1016/j.tetlet.2015.01.167.

Gram-scale, chemoselective synthesis of N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC)

Noah A Setterholm  1 , Frank E McDonald  1 , Jeffrey H Boatright  2 , P Michael Iuvone  3
Affiliations

Gram-scale, chemoselective synthesis of N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC)

Noah A Setterholm et al. Tetrahedron Lett. .

Abstract

N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC) is a potent activator of the TrkB receptor in mammalian neurons and of interest because of its potential therapeutic uses. In the absence of a commercial supply of HIOC, we sought to produce several grams of material. However, a synthesis of HIOC has never been published. Herein we report the preparation of HIOC by the chemoselective N-acylation of serotonin, without using blocking groups in the key acylation step.

Keywords: activation; amide; chemoselectivity; decarboxylation; kinase; serotonin; synthesis.

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Figures

Figure 1
Figure 1. Structures of serotonin and derivatives, including HIOC (3)
Figure 2
Figure 2. Retrosynthesis of HIOC
Scheme 1
Scheme 1. Preparation and isolation of 2-oxo-3-piperidinecarboxylic acid (4)
Scheme 2
Scheme 2. Acylation of serotonin with carboxylic acid 4
Scheme 3
Scheme 3. Optimized acylation for the synthesis of HIOC (3)
See this image and copyright information in PMC

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