Methyl 2-amino-3-thenoate → Methyl 2-(3-ethoxy-3-oxopropanamido)thiophene-3-carboxylate

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Reaction Steps

A preferred intermediate in the preparation of compounds of structure (III) is 4-chloro-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester, depicted by formula (42) below. To prepare this intermediate, methyl-2-amino-thiophene-3-carboxylate was reacted with ethylmalonyl chloride to yield intermediate 2-(2-ethoxycarbonyl-acetylamino)-thiophene-3-carboxylic acid methyl ester, depicted by formula (39). This intermediate was converted to 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester, depicted by formula (40), by reacting it with sodium ethoxide, and then converting it into 4,6-dichloro-thieno[2,3-b]pyrdine-5-carboxylic acid ethyl ester, depicted by formula (41). Hydrolysis of 4,6-dichloro-thieno[2,3-b]pyrdine-5-carboxylic acid ethyl ester, depicted by formula (41), yielded 4-chloro-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester, depicted by formula (42), as shown in Scheme 20.

Provenance & Evidence