Synthetic method of non-steroidal antiinflammatory drug pain killing

Abstract

The invention discloses a synthesis method of non-steroidal anti-inflammatory drug tolmetin. The methodcomprises the following steps: sequentially preparing a sulfuric acid-containing acetonedicarboxylic acid crude product, 2-(2-acetoxy)-1-methyl-1H-pyrrole-3-formic acid and 2-(2-alkyl acetate)-1-methyl-1H-pyrrole-3-formic acid by taking citric acid or citric acid monohydrate as a raw material; and carrying out decarboxylation, acylation, hydrolysis and acidification to obtain tolmetin. The synthetic method provided by the invention overcomes the defect that the existing tolmetin preparation process depends on N-methylpyrrole, and is a low-cost, low-pollution and high-yield synthetic method of non-steroidal anti-inflammatory drug tolmetin.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a method for synthesizing a non-steroidal anti-inflammatory drug acetidine. Background technique [0002] Tolmetin, chemical name: 1-methyl-5-(p-methylbenzoyl)pyrrole-2-acetic acid, is a non-steroidal anti-inflammatory analgesic, developed by McNeil Company of the United States, in 1976 Approved by the US FDA for marketing. Its effect is similar to that of other non-steroidal anti-inflammatory drugs such as aspirin, but the side effects are relatively mild, and it is easier to be tolerated by patients. Animal experiments have proved that its anti-arthritis effect is stronger than that of aspirin, but weaker than indomethacin and phenylbutazone. Its analgesic effect is equivalent to that of ibuprofen, and its antipyretic effect is also strong. It can be absorbed quickly and safely after oral administration. [0003] At present, the synthetic route of Pamonadine mainly contains the ...

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Problems solved by technology

However, in this method, N-methylpyrrole is used as a raw material, and the process cost is high

[0009] (6) U.S. Patent US4363918 protects the preparation of 2-(2-acetoxy)-1-methyl-1H-pyrrole-3-carboxylic acid using acetone dicarboxylic acid, methylamine and chloroacetaldehyde, but does not give specific implementation method

Moreover, acetone dicarboxylic acid is a very unstable crystal, which is easily decomposed by heating, is not suitable for storage, is expensive, and has a poor degree of commercialization. Using acetone dicarboxylic acid as a starting material cannot realize the industrialized production of pemetidine

[0010] Most of the existing published synthetic routes of pemetidine rely on N-methylpyrrole, and the sharp rise in the market price of N-methylpyrrole has significantly reduced the economic benefits of the pemethadine process

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