1349649-83-7Relevant academic research and scientific papers
A highly stereoselective and efficient synthesis of enantiomerically pure sitagliptin
Kang, Sung Kwon,Cho, Gyeong Hi,Leem, Hyung Joon,Soh, Bong Kwan,Sim, Jaehoon,Suh, Young-Ger
, p. 34 - 40 (2017)
A highly stereoselective and efficient synthesis of sitagliptin 1 consisting of a chiral β-amino acid unit has been achieved through 6 steps from commercially available 2,4,5-trifluorobenzaldehyde 4. The chiral antidiabetic drug was obtained with almost perfect enantiomeric purity (>99.9% ee) in 40.9% overall yield. The key feature of the synthesis is the addition of a malonate enolate to a chiral sulfinylimine in more than 99:1 dr. Our synthetic procedure proved to be highly efficient, economical, and sustainable.
Synthesis method of sitagliptin
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, (2018/08/03)
The invention discloses a synthesis method of sitagliptin. The synthesis method comprises the following steps: 1) 3-oxopropionic acid is adopted as a starting raw material to react with an acylating chlorination reagent to obtain corresponding acyl chloride, then the obtained acyl chloride reacts with 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazol(4,3-a)pyridazine hydrochloride to obtain anamide compound III; 2) the compound III and R-(+)-tertbutylsulfenamide are condensed to obtain an acetal compound IV; 3) the compound IV and 2,4,5-trifluorophenylmethyl magnesium bromide are added toobtain a compound V; 4) the compound V is treated by acid deprotection to obtain a compound I, i.e., sitagliptin. The synthesis method disclosed by the invention has the beneficial effects that the steps are fewer, the operation is simple, and the use of an expensive chiral catalyst is avoided, so that the cost is reduced; the obtained product is high in purity, so that the synthesis method is suitable for industrial production.
Sitagliptin synthesis method
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, (2018/07/07)
The invention discloses a sitagliptin synthesis method, which comprises: carrying out a reaction on a compound represented by a formula IV, (R)-(+)-tert-butyl sulfinamide and hydrogen under the catalysis of a catalyst to obtain a compound represented by a formula V; and carrying out a hydrolysis reaction on the compound represented by the formula V to obtain a compound represented by a formula VI,ie., sitagliptin. According to the present invention, the method has advantages of easily available raw materials, simple steps, high yield and mild reaction conditions, and is suitable for industrial production. The formulas IV, V and VI are defined in the specification.
NOVEL BETA-SULFINAMINO MALONATE DERIVATIVES AND PROCESS FOR PREPARING THE SAME, AND PROCESS FOR PREPARING SITAGLIPTIN USING THE SAME
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, (2021/06/22)
The present invention relates to beta-sulfinamino malonate derivatives having a high diastereomeric ratio (DR) value manufactured through a stereoselective addition reaction of chiral sulfinyl imine and malonate derivatives, to optically pure Sitagliptin by using the same, and to a method for manufacturing pharmaceutically acceptable salt thereof. According to the present invention, the method is capable of manufacturing novel beta-sulfinamino malonate derivatives which are intermediate in the manufacture of Sitagliptin, with high optical purity and high yields without using a solvent under mild conditions, and ultimately manufacturing optically pure Sitagliptin in an efficient manner by using the same.COPYRIGHT KIPO 2016
A method for synthesizing row sandbank west he
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, (2017/04/13)
The invention discloses a synthetic method for sitagliptin. The method comprises the following steps that: 2,4,5-trifluorobenzaldehyde is used as a starting raw material and undergoes the Wittig reaction and hydrolysis with hydrochloric acid so as to obtain 2-(2,4,5-trifluorophenyl)acetaldehyde; 2-(2,4,5-trifluorophenyl)acetaldehyde and (R)-(+)-t-butyl sulfenamide are subjected to condensation so as to obtain corresponding acetal; acetal and ethyl bromoacetate undergo the Reformatsky reaction, and then an obtained product undergoes hydrolysis so as to obtain organic acid; the organic acid and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride are subjected to condensation so as to obtain acetal of t-butyl sulfenamide of sitagliptin; and finally methanol hydrochloride is used for deprotection so as to obtain sitagliptin. The invention has the following advantages: yield in each step is high, operation is simple, reagents used in the method are conventional reagents, usage of an expensive chiral catalyst is avoided, and good industrial prospect is obtained.
NOVEL SULFUR CONTAINING COMPOUNDS
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Page/Page column 53, (2011/12/02)
Novel sulfur containing compounds are disclosed as intermediates for preparation of a Sitagliptin of formula V. A novel synthetic method to prepare Sitagliptin using the said intermediates is also disclosed.
