881995-69-3Relevant academic research and scientific papers
Synthesis method of sitagliptin free alkali and sitagliptin phosphate monohydrate
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, (2021/07/24)
The invention relates to a synthesis method of sitagliptin free alkali and sitagliptin phosphate monohydrate. According to the method, dry HOBt is removed or changed into HOBt hydrate, a solvent DMF is removed in the process, and a simple solvent easy to recover is used in the production process, so that the production cost is reduced, and the reaction safety is improved. According to the invention, with the in-situ process from a compound represented by a formula 2 to a compound represented by a formula 6, the yield can be improved, the operation steps can be reduced, and the methanol or isopropanol IPA is replaced with other solvents so as to avoid the generation of impurities represented by a formula 7, a formula 8 and a formula 9, such that the product purity and the yield can be substantially improved, and the HPLC purity of the sitagliptin free alkali is more than 99%.
A west he row sandbank chiral intermediate and asymmetric synthesis method
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, (2017/08/25)
The invention relates to a sitagliptin chiral intermediate and an asymmetric synthesis method thereof. The asymmetric synthesis method comprises the steps: with 2,4,5-trifluorophenyl acetic acid as a starting material, carrying out a reduction reaction to obtain 2-(2,4,5-trifluorophenyl)ethanol, then carrying out a reaction with an oxidant, carrying out condensation of the product without separation and (R)-(+)-tert-butyl sulfinamide to obtain corresponding acetal, carrying out a reaction of the obtained product with dialkyl malonate to obtain a key chiral intermediate, hydrolyzing to obtain a corresponding organic amine, carrying out a reaction of the amine with caustic alkali and then acidifying to obtain a corresponding carboxylic acid, then carrying out condensation with 3-(trifluoromethyl)-5,6,7,8- tetrahydro-[1,2,4] triazolo[4,3-a]pyrazine hydrochloride to obtain sitagliptin tert-butyl oxanamide, and finally deprotecting with hydrochloric acid to obtain sitagliptin. The yields of all the steps are all higher, the used reagents are all conventional cheap reagents, no expensive chiral catalysts are used, the reaction conditions are quite mild, and the asymmetric synthesis method is suitable for industrialization.
Purpose of compound for preparing Sitagliptin and Sitagliptin preparation method
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Paragraph 0044; 0045; 0046; 0047, (2017/10/31)
The invention provides a compound shown by a formula I, a purpose of a stereoisomer, a geometrical isomer, a tautomer, an oxynitride, a hydrate, a solvate, a metabolite, a pharmacologically acceptable salt or prodrug of the compound in Sitagliptin preparation, and a Sitagliptin preparation method. The formula I is shown in the description, wherein R1 is a substitutional group containing the hydroxyl group. The compound shown by the formula I or the stereoisomer, the geometrical isomer, the tautomer, the oxynitride, the hydrate, the solvate, the metabolite, the pharmacologically acceptable salt or the prodrug of the compound shown by the formula I has high water solubility, and is used for obtaining a chiral amino intermediate to further obtain the Sitagliptin. Compared with the prior art, the compound has the advantages that the amino group conversion rate is greatly improved; the yield of the Sitagliptin is also greatly improved.
Method for synthesizing sitagliptin intermediate
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, (2016/10/24)
The invention relates to a method for synthesizing a sitagliptin intermediate. The method is characterized in that asymmetric reduction ammonification of a compound of formula II and ammonia or ammonium salt in the presence of a chiral phosphorus coordinated transition metal catalyst in an appropriate organic solvent containing an acidic additive to obtain a compound of formula I. The R- or S- configuration of a stereocenter is represented by *, and the formula I with the R configuration can be used to prepare sitagliptin. A reaction equation is shown in the description; and R and R in the reaction equation are respectively independently selected from hydrogen, C1-C12 linear or branched alkyl groups, C3-C12 cycloalkyl groups, C2-C12 alkene groups, C2-C12 alkynyl groups and C7-C12 arylalkyl groups. The method has the advantages of high yield and ee% value, mild reaction conditions, simple operation, convenient purification, low production cost, environmental protection, and suitableness for industrial production.
Substrate screening of amino transaminase for the synthesis of a sitagliptin intermediate
Hou, Anwei,Deng, Zixin,Ma, Hongmin,Liu, Tiangang
, p. 4660 - 4664 (2016/07/15)
We reported herein a new enzymatic route to synthesize a sitagliptin intermediate using an aminotransferase. Substrate profile indicated that hydroxyethyl-3-oxo-4-(2,4,5-trifluorophenyl)butanoate, among 11 analogs, showed the best biocatalytic performance, partially due to its best solubility in the enzymatic system. The corresponding amino esters showing strong product inhibition on the reaction, were inclined to autohydrolyze, thus driving the reaction forward, which indicated the contribution of the rapid hydrolysis of hydroxyethyl ester to the biocatalytic performance. The reaction was performed at 100?mM with 82% conversion in 24?h. The amino ester product was further transformed to Boc-(R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid, the key intermediate of sitagliptin.
A NOVEL PROCESS FOR THE PREPARATION OF SITAGLIPTIN
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, (2013/08/15)
The present invention is directed to a process for the preparation of enantiomerically enriched β-amino acid derivatives which are important chiral building blocks and intermediates in pharmaceuticals. More specifically, the invention pertains to a novel process for practically convenient and economically producing enantiomerically enriched β-amino acid derivatives which are useful for the synthesis of amide inhibitors of dipeptidyl peptidase IV like Sitagliptin, which have been used to treat type 2 diabetes.
SITAGLIPTIN SYNTHESIS
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, (2012/05/07)
The present invention relates to novel processes for the preparation of enantiomerically enriched β-amino acid derivatives such as β-amino esters useful for the synthesis of enantiomerically enriched biologically active molecules such as sitagliptin. The key step involves the resolution of the racemate with mandelic acid.
PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND ITS INTERMEDIATES
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Page/Page column 52, (2010/11/05)
The present invention relates to novel and improved processes for the preparation of Sitagliptin compound of formula (1) and its intermediates.
The asymmetric synthesis of Sitagliptin, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Liu, Feng,Yu, Wansheng,Ou, Wenhua,Wang, Xiaoke,Ruan, Libo,Li, Yiming,Peng, Xijiang,Tao, Xiaohu,Pan, Xianhua
experimental part, p. 230 - 232 (2010/08/04)
An efficient asymmetric synthesis of Sitagliptin, a new DPP-IV inhibitor for the treatment of type 2 diabetes mellitus has been developed. The beta-amino acid fragment of Sitagliptin was prepared by asymmetric Michael addition of the corresponding α, β-unsaturated ester to (R)-(α-methylbenzyl) benzylamine followed by a two-step elaboration to obtain N-boc beta-amino ester. Hydrolysis of the ester and coupling with the triazolopiperazine afforded Sitagliptin after cleavage of the N-boc group and salt formation. The overall yield was 31% over nine steps.
SITAGLIPTIN SYNTHESIS
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Page/Page column 28, (2010/12/17)
The present invention relates to novel processes for the preparation of enantiomerically enriched β -amino acid derivatives such as β -amino esters useful for the synthesis of enantiomerically enriched biologically active molecules such as sitagliptin. The key step involves the resolution of the racemate with mandelic acid.
