Thienopyridine analogues of papaverine

Lawson, B., 1978. Thienopyridine analogues of papaverine. PhD, Nottingham Trent University.

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Abstract

This thesis reports attempts to prepare the thiophene analogue of papaverine in which the dimethoxy isoquinoline system is replaced by a dimethoxy thienopyridine.

In the first approach the intention was the preparation of a 4-substituted 3-methoxy thieno[3,2-c]pyridine, starting from ethyl 4-hydroxy-2-thienylacetate, for which a synthesis had been published. However, on repeating this preparation it was found that the product was actually ethyl 3-hydroxy-5-methyl thiophene-2-carboxylate.

Alternative routes to the desired methoxy thienopyridine system involving the reactions of 5-methoxythiophene-2-carboxaldehyde, substituted 2-iodo thiophene and substituted pyridine systems were then followed. Unfortunately all proved unsuccessful.

In another approach the intention was to introduce the methoxy group into a thienopyridine system by adaptation of published procedures. Thus, in one instance, 3-iodo-7-methyl thieno[2,3-c] pyridine was reacted with sodium methoxide in the presence of copper oxide, giving a product which appeared to contain some of the desired methoxylated thienopyridine. However, the reaction could not be brought to completion.

In a final approach, cyclisation of the amides formed by condensation of β-(4-methoxy-2-thienyl)ethylamine with phenylacetic acid, 4-methoxyphenyl- and 3,4-dimethoxyphenylacetic acids was attempted, giving in each case the appropriate dihydrothieno[3,2-c]pyridine.

Further reaction of one of these, 3-methoxy-4-(3'4'- dimethoxybenzyl)-6,7-dihydrothieno[3,2-c]pyridine, with activated manganese dioxide gave a product which was identified as 3-raethoxy-4-(3'4'-dimethoxybenzoyl)-6, 7-dihydrothieno[3,2c] pyridine. Reduction of this compound gave a material imperfectly characterised as the corresponding carbinol.

As an extension of the project, several attempts were made to prepare a methoxy thienylacetic acid in the hope that such an acid could be condensed with β-(4-methoxy-2-thienyl)ethylamine to give, at the end of the synthesis, a true thiophene analogue of papaverine. Unfortunately, insufficient, time was available to carry this through to completion.

Item Type:	Thesis
Creators:	Lawson, B.
Date:	1978
ISBN:	9781369324907
Identifiers:	Number Type PQ10290241 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	24 Jun 2021 09:33
Last Modified:	26 Oct 2023 08:32
URI:	https://irep.ntu.ac.uk/id/eprint/43183

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