Methyl 2-amino-3-thenoate → Methyl 2-(3-ethoxy-3-oxopropanamido)thiophene-3-carboxylate
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])NC2SC=CC=2C=1Cl)=[O:5])[CH3:2].[CH3:17][O:18][C:19]([C:21]1[CH:25]=[CH:24][S:23][C:22]=1[NH2:26])=[O:20].C(C(C(Cl)=O)C(Cl)=O)C>>[CH3:17][O:18][C:19]([C:21]1[CH:25]=[CH:24][S:23][C:22]=1[NH:26][C:11](=[O:12])[CH2:6][C:4]([O:3][CH2:1][CH3:2])=[O:5])=[O:20]Participants
Procedure
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.
Sources & evidence
- ORD record
- ord-b9e232f803bf4f6ebabeddf91bc2993f
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07365200B2
Reaction notes
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