75143-89-4Relevant articles and documents
Development of a new synthesis approach for S-pregabalin by optimizing the preparation stages
Mansoori, Arsalan,Zahednezhad, Fahimeh,Bavili Tabrizi, Ahad,Shahbazi Mojarrad, Javid
, p. 89 - 101 (2019/09/13)
In the present study, we aimed to optimize the synthesis stages of S-pregabalin ((S)-3-(aminomethyl)-5-methylhexanoic acid), a well-known anticonvulsant drug. We used appropriate solvents and compounds to reach a straightforward and applicable method. The advantages of this research were avoiding use of expensive and environment pollutant reagents and solvents, and also using a recoverable reagent. Discarding prevention of the intermediates and reagents besides attaining a higher yield of the obtained product were the additional achievements. All structures were characterized by FT-IR, 1H NMR, and the purity of S-pregabalin was evaluated using the HPLC assay.
Pregabalin intermittent synthesis method
-
Paragraph 0014; 0018, (2019/02/21)
The invention discloses a pregabalin intermittent synthesis method. The method comprises the following step of (1) preparation of 2-cyano-5-methyl-2-hexenyl ethyl ester (A), wherein 94.6 g (1.1mol) ofisovaleraldehyde, 113 g (1.0 mol) of ethyl cyanoacetate, 127 ml of n-hexane and 1.00 g (0.01mol) of di-n-propylamine are put into a 1000 ml reaction bottle in sequence, heating is conducted, reflux reaction is carried out, a water separator is used for water separation, the reaction is carried out until no moisture is separated out, and cooling is conducted. Compared with the prior art, the pregabalin intermittent synthesis method has the following advantages that when methyl tertiary butyl ether is used as a solvent, layering is hard, impurities cannot be removed, the solvent cannot be recycled, the raw material cost is improved, and the amide is low, so that the methyl tertiary butyl ether is not suitable for being used as the solvent; ethyl acetate can be used, however, the intersolubility of the ethyl acetate and water is large, thus a small amount of amide crude product is dissolved in the water, the amide yield is low, meanwhile, the ethyl acetate recovery is low, and by using methylbenzene, the defects of the ethyl acetate are avoided, so that the methylbenzene is selected as an ammoniation solvent. There are no corresponding HPLC standards of the quality situation of amide, however, the quality of the amide obtained by adopting a technology is qualified in later detection.
Preparation method of pregabalin intermediate (R)-3-carbamoyl methyl-5-methylhexanoic acid
-
Paragraph 0009; 0010, (2019/10/02)
The invention relates to a preparation method of key intermediate (R)-3-carbamoyl methyl-5-methylhexanoic acid of pregabalin treating epilepsy, neuropathic pain and anxiety. The method uses cyanoacetamide and isovaleraldehyde as starting materials to prepare 3-isobutylglutaric acid, 3-isobutylglutaric acid is esterified, enzymatically reacted and aminolyzed to produce the pregabalin intermediate (R)-3-carbamoyl methyl-5-methylhexanoic acid. The invention has the advantages of low cost, simple reaction, environmental friendliness and high yield, and is suitable for industrial production.