- Preparation method of sitagliptin intermediate
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The invention belongs to the field of pharmaceutical synthesis, and particularly relates to a preparation method of a sitagliptin intermediate. The preparation method includes the steps of 1) acylating chlorination reaction: enabling 2,4,5-trifluorophenylacetic acid to directly react with sulfoxide chloride to generate a compound II; 2) Grignard reagent preparation: adding a compound III and magnesium chips, and triggering with iodine to obtain a Grignard reagent compound IV; 3) Grignard reaction: taking cuprous iodide as a catalyst, subjecting the compound II and the Grignard reagent compound IV to Grignard reaction to generate the sitagliptin intermediate-a compound V. The preparation method of the sitagliptin intermediate is simple in synthetic route, capable of producing highly-pure product, high in yield, low in cost, mild in reaction conditions, and applicable to industrialized production.
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Paragraph 0034; 0038-0048
(2017/11/18)
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- SITAGLIPTIN, SALTS AND POLYMORPHS THEREOF
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The present invention relates to an improved process for preparation of Sitagliptin or pharmaceutically acceptable salts thereof. The present invention further relates to novel polymorphs of Sitagliptin salts and process for preparation thereof.
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Paragraph 0156; 0157; 0158; 0159; 0160
(2013/06/28)
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- PROCESSES FOR THE PREPARATION OF R-SITAGLIPTIN AND INTERMEDIATES THEREOF
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The present invention relates to the synthesis of R-sitagliptin. The present invention also relates to a compound of formula (IV) or its salt, that are useful as key intermediate in the synthesis of R-sitagliptin or pharmaceutically acceptable salts thereof.
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Page/Page column 27
(2012/04/17)
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- SITAGLIPTIN SYNTHESIS
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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.
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- SITAGLIPTIN, SALTS AND POLYMORPHS THEREOF
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The present invention relates to an improved process for preparation of Sitagliptin or pharmaceutically acceptable salts thereof. The present invention further relates to novel polymorphs of Sitagliptin salts and process for preparation thereof.
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Page/Page column 29-30
(2012/03/26)
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- PROCESS AND INTERMEDIATES FOR THE PREPARATION OF N-ACYLATED-4-ARYL BETA-AMINO ACID DERIVATIVES
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A process for producing an enantiomerically enriched, pure or enriched and essentially pure compound of Formula I [structure] wherein the R-, or S-configuration at the stereogenic center is marked with an *, which process hydrogenates an enamide compound of formula III [structure] in an organic solvent in the presence of a transition metal precursor complexed to a chiral phosphine ligand catalyst, wherein Ar is phenyl which is unsubstituted or substituted, R1 and R2 are selected from H, Cl - 8 alkyl, C5 - 12 cycloalkyl, aryl and aryl-C 1 - 2-alkyl, or R1 and R2 together with the nitrogen atom to which they are attached form a C4- r member heterocyclic πng system optionally fused with a 5- to 6- member carbocyclic or heterocyclic ring system, and the other substituents are as defined herein.
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Page/Page column 17
(2010/08/04)
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- SITAGLIPTIN SYNTHESIS
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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.
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Page/Page column 26
(2010/12/17)
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- PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND ITS INTERMEDIATES
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The present invention relates to novel and improved processes for the preparation of Sitagliptin compound of formula (1) and its intermediates.
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Page/Page column 65
(2010/11/05)
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- Synthesis, biological evaluation and structural determination of β-aminoacyl-containing cyclic hydrazine derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors
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Inhibitors of dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes. A series of β-aminoacyl-containing cyclic hydrazine derivatives were synthesized and evaluated as DPP-IV inhibitors. One member of this series, (R)-3-amino-1-(2-benzoyl-1,2-diazepan-1-yl)-4-(2,4,5-trifluorophenyl)but an-1-one (10f), showed potent in vitro activity, good selectivity and in vivo efficacy in mouse models. Also, the binding mode of compound 10f was determined by X-ray crystallography.
- Ahn, Jin Hee,Shin, Mi Sik,Jun, Mi Ae,Jung, Sun Ho,Kang, Seung Kyu,Kim, Kwang Rok,Rhee, Sang Dal,Kang, Nam Sook,Kim, Sun Young,Sohn, Sang-Kwon,Kim, Sung Gyu,Jin, Mi Sun,Lee, Jie Oh,Cheon, Hyae Gyeong,Kim, Sung Soo
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p. 2622 - 2628
(2008/02/11)
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- Application of the asymmetric hydrogenation of enamines to the preparation of a beta-amino acid pharmacophore
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(3R)-3-[N-(tert-Butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 7a has been synthesized by an asymmetric hydrogenation of enamine ester 3 using chiral ferrocenyl ligands I and II in conjunction with [Rh(COD)Cl] 2. The direct reduction of 3 provides amino ester 1b in 93% ee, which was isolated as an (S)-camphorsulfonic acid salt to upgrade the enantiomeric excess to >99%. A more concise approach was developed involving the in situ protection of 1b using di-tert-butyldicarbonate. This approach provided the desired N-Boc amino ester 7b directly from the hydrogenation with 97% ee, which was upgraded to >99% ee upon crystallization.
- Kubryk, Michele,Hansen, Karl B.
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p. 205 - 209
(2007/10/03)
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