Browse Prior Art Database

Impurities Formed in a Process for Preparing (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide

IP.com Disclosure Number: IPCOM000179307D
Publication Date: 2009-Feb-12
Document File: 2 page(s) / 72K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 66% of the total text.

Page 1 of 2

Impurities Formed in a Process for Preparing
(S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide

(S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide, of the following formula:

O N

H

O

I

is the first in a new class of sleep agents that selectively binds to the melatonin receptors in the suprachiasmatic nucleus (SCN), versus binding to GABA receptors, such as with other commercial drugs.

Provided are two impurities formed in a process for preparing (S)-N-[2-(1,6,7,8- tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide: (E)-3-(2,3- dihydrobenzofuran-7-yl)acrylic acid, compound I, of the following formula:

O

HO

O

IV-IA ,

and 3-(2,3-dihydro-1-benzofuran-7-yl)propanoic acid, compound II, of the following formula:

O

HO

O

V-IA .

Page 2 of 2

In the provided below procedure, compound I is prepared using a Knoevenagel condensation.

Procedure 1:

A mixture of 2,3-dihydrobenzofuran-7-carbaldehdye (100.0 g, 0.6756 mol) and malonic acid (175.67 g, 1.689 mol) in pyridine (200 ml) containing piperidine (11.5 g, 0.135 mol) and acetic acid (4.05 g, 0.0675 mol) was heated at 100°C for 4-5 hours. The cooled reaction mixture was poured into HCl-water with stirring after completion of reaction. The reaction mass was stirred for 2-3 hours at room temperature and then the solid mass was filtered and dried under vacuum (5-10 mmHg) at 60-70°C.

In the provided below procedure, compound II is prep...