Synthesis of 5-substituted 5-hydroxy-2-pyrrolidones, metabolites of the antipsychotic benzamide remoxipride |
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Authors: | L Gawell C E Hagberg T H?gberg M Widman |
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Institution: | Department of Medicinal Chemistry, CNS 2, S?dert?lje, Sweden. |
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Abstract: | This paper describes the synthesis of 5-(3-bromo-2,6-dimethoxybenzamido)-methyl]-5-hydroxy-2-pyrrolidon e (3) and its 1-ethyl analogue 2, two urinary metabolites of the dopamine D-2 antagonist remoxipride 1, (S)-3-bromo-N-(1-ethyl-2-pyrrolidinyl)methyl]-2, 6-dimethoxybenzamide]. Two synthetic schemes leading to a common intermediate, 5-benzamido-4-oxopentanoic acid 4, were developed. This key intermediate permits conversion into either metabolite. Reaction of 4 with isobutyl chloroformate furnished a mixed carbonic anhydride, which upon treatment with ethylamine or ammonia gave the 4-oxopentanamides 5 and 6, respectively. Ring-closure afforded the corresponding 5-hydroxy-2-pyrrolidones 2 and 3. |
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