cas 654671-78-0, Sitagliptin phosphate | Articles data

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Two methods for the preparation of sitagliptin phosphate: Via chemical resolution and asymmetric hydrogenation
Two effective processes have been developed for the preparation of sitagliptin phosphate. The approach of chemical resolution obtained R-sitagliptin in five steps from commercially available starting materials using the inexpensive NaBH4 to reduce the enamine and then using (-)-di-p-toluoyl-l-tartaric acid to resolve racemates in 11% yield overall. The route successfully avoids the use of expensive noble metal as catalysts compared with traditional synthesis methods, resulting in greatly reduced costs and simplified synthetic routes. Other alternative asymmetric hydrogenation of β-ketomide routes for the synthesis of sitagliptin were found, two of the intermediates were synthesized for the first time. This journal is
Ye, Fei,Zhang, Zhifeng,Zhao, Wenxia,Ding, Jianhai,Wang, Yali,Dang, Xueyan
p. 4805 - 4809
(2021/02/03)

Preparation method of sitagliptin phosphate monohydrate crystal form
The invention relates to a preparation method of a sitagliptin phosphate monohydrate crystal form. The method comprises the following steps: adding sitagliptin free alkali, phosphoric acid, water and a specific organic solvent into a reactor, and reacting
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Paragraph 0022-0057

(2021/05/05)

IMPROVED PROCESS FOR PREPARATION OF SITAGLIPTIN
Provided herein is a process for the preparation of specific enantiomeric Sitagliptin with good chiral purity and higher yield using improved biocatalyst and by engineering an enzyme to mediate the efficient conversion of ketoamide to obtain enantiomerically pure Sitagliptin in presence of an amino group donor.
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Page/Page column 16

(2021/12/31)

Synthesis of (?)-(R)-Sitagliptin by RhI-Catalyzed Asymmetric Hydroamination
We report of a concise synthesis of (R)-sitagliptin monophosphate – a drug predominantly applied in the treatment of type 2 diabetes. Utilizing our recently developed RhI-catalyzed hydroamination of allenes for the stereoselective construction of the inherent chiral amino function, a new approach to (R)-sitagliptin monophosphate on a 3.5 mmol scale was established.
Berthold, Dino,Breit, Bernhard
p. 6247 - 6249
(2021/09/25)

Process for preparing sitagliptin
The present technology relates to a method for manufacturing sitagliptin, which is a representative drug among DPP-4 inhibitors which are drugs used for the treatment of diabetes. The method of the present invention uses CDI for the condensation reaction of specific compounds, and through a specific subsequent process, high-purity sitagliptin phosphate monohydrate can be manufactured in a high yield. In particular, the manufacturing method of the present invention is suitable for mass production.
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Paragraph 0053-0055

(2021/06/01)

Preparation method of sitagliptin phosphate anhydrous hydrate
The invention relates to a preparation method, of a crystal form of sitagliptin phosphate anhydrous crystal, which is used for preparing sitagliptin phosphate anhydrous crystal form, with high yield, purity, particles after heating the solution, filtering
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Paragraph 0029-0038

(2020/03/12)

Preparation method of sitagliptin phosphate
The invention discloses a preparation method of sitagliptin phosphate. The preparation method comprises the following steps: taking 4-(2, 4, 5-trifluorophenyl)-3-methyl oxobutyrate I as a raw material; the reaction is mainly divided into five steps: carrying out asymmetric reduction on the raw material I through an N-heterocyclic carbene palladium catalyst to obtain chiral alcohol ester s-4-(2, 4,5-trifluorophenyl)-3-methyl hydroxybutyrate II; carrying out intramolecular condensation cyclization on the II to obtain chiral lactam quaternary ring (R)-N-benzyloxy-4-[1-methyl-(2, 4, 5-trifluorophenyl)]-2-azetidinone III; carrying out ring opening on the III under an alkaline condition to obtain IV; performing condensation reaction to form amide to obtain V; carrying out catalytic reduction onthe V through recycled N-heterocyclic carbene palladium to remove benzyloxy and form phosphate to obtain sitagliptin phosphate VI, wherein the N-heterocyclic carbene palladium catalyst is Pd (IPr-NHC) (acac) Cl or Pd (IPr-NHC) (acac) Oac or Pd (IPr-NHC) (dba) Cl or Pd (IPr-NHC) (dba) OAc; the catalyst is cheap and easily available, can be recycled, and is beneficial to batch production.
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(2020/10/14)

PROCESSES FOR THE PREPARATION OF SITAGLIPTIN AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
The present application relates to improved processes for the preparation of Sitagliptin and pharmaceutically acceptable salts thereof. The present application also relates to the improved crystallization process for the preparation of Sitagliptin Phosphate. The present application also relates to the improved crystallization process for the preparation of Sitagliptin Hydrochloride monohydrate.
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Page/Page column 18-19

(2020/06/19)

Synthesis of (R)-3-(tert-Butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic Acid, a Key Intermediate, and the Formal Synthesis of Sitagliptin Phosphate
An alternate formal synthesis of Sitagliptin phosphate is disclosed from 2,4,5-trifluorobenzadehyde in 8 linear steps with an overall yield of 31%. The chiral β-amino acid moiety present in sitaglitpin is installed via an asymmetric hydrogenation followed by a stereoselective Hofmann rearrangement as the key steps. The key chiral intermediate Boc-amino acid 1 prepared by this novel route was further converted to Sitagliptin phosphate following the known literature protocol.
Achanta, Srinivas,Bandichhor, Rakeshwar,Chaudhari, Pramod S.,Cobley, Christopher J.,Dahanukar, Vilas,Llewellyn-Beard, Fiona,Sreenivasulu, Kurella,Sud, Abhishek
(2020/05/08)

Preparation method of Sitagliptin phosphate monohydrate crystal form
The invention relates to a preparation method of a Sitagliptin phosphate monohydrate crystal form, and the method specifically comprises the following steps: taking water as a solvent, heating, dissolving, cooling, carrying out suction filtration, and dry
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Paragraph 0055-0059

(2019/04/30)

Practical asymmetric synthesis of Sitagliptin phosphate monohydrate
Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed by a tandem aza-Michael/hemiacetal reaction catalyzed by an organocatalyst and the influence of acidity of Br?nsted acid on tandem aza-Michael/hemiacetal reaction is researched in detail.
Gao, Haoling,Yu, Jiangang,Ge, Chengsheng,Jiang, Qun
(2018/06/29)

A west he row sandbank and its salt synthesis method (by machine translation)
The invention discloses a west he row sandbank and its salt synthesis method, in order to 2, 4, 5 - trifluorobenzene acetic acid as the starting material, through esterification, reduction, oxidation and Witting reaction, to obtain 4 - (2, 4, 5 - trifluorophenyl) - 2 - butene ethyl ester, or passes through the reduction, oxidation and Witting reaction after, to obtain 4 - (2, 4, 5 - trifluorophenyl) - 2 - butene ethyl ester. Then in BuLi or six methyl two silicon and nitrogen under the action of the alkane-sodium, with chiral amine on the hydroamination reaction, framed asymmetric amination product, through ester, condensation, hydrogenated three-step reaction to obtain sitagliptin. The west he of the spit of fland synthesis method of raw materials are cheap and easy to obtain, steps are less, the operation is easy, can be effectively reduced. The method can be the high purity of the sitagliptin, the salt of the phosphoric acid obtained after HPLC purity and sitagliptin ee values are in 99% or more, can be applied to the medical field. (by machine translation)
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(2017/08/04)

A PROCESS FOR PREPARING 7-[(3R)-3-AMINO-1-OXO-4-(2,4,5TRIFLUOROPHENYL)BUTYL]- 5,6,7,8-TETRAHYDRO-3-(TRIFLUOROMETHYL)-1,2,4-TRIAZOLO[4,3-A]PYRAZINE PHOSPHATE MONOHYDRATE AND ITS NOVEL CRYSTALLINE FORM H
The present invention discloses the process for preparation of 7-[(3R)-3-amino-1-oxo-4- (2,4,5trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3- a]pyrazine phosphate monohydrate.
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Page/Page column 6; 8

(2017/01/26)

NOVEL PROCESS FOR THE PREPARATION OF DIPEPTIDYL PEPTIDASE-4 (DPP-4) ENZYME INHIBITOR
The present invention relates to a novel and improved process for the preparation of Sitagliptin of Formula (I) and its pharmaceutically acceptable salts. The present invention also relates to novel intermediates and process for the preparation of intermediates used in the preparation of Sitagliptin.
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(2016/08/10)

Improved method of sitagliptin
The present invention relates to an improved method for manufacturing sitagliptin, comprising a step of preparing N-Boc protected sitagliptin using diphenyl phosphite suitable for mass production as a reagent and a deprotection step.
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Paragraph 0064; 0065

(2017/06/02)

Crystal of dipeptidyl peptidase-4 inhibitor
The invention provides a crystal of a dipeptidyl peptidase-4 inhibitor. Specifically, the invention provides a phosphate crystal of 7-[(3R)-3-amino-1-oxo-4-(2, 4, 5-trifluorophenyl)butyl]-5, 6, 7, 8-tetrahydro-3-trifluoromethyl-1, 2, 4-triazolo[4, 3-a]pyr
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Paragraph 0026; 0027

(2017/03/14)

EXPEDIENT SYNTHESIS OF SITAGLIPTIN
Novel intermediates are disclosed as intermediates for preparation of a Sitagliptin. A novel synthetic method to prepare Sitagliptin using the said intermediates is also disclosed.
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(2015/09/23)

Synthesis of sitagliptin phosphate by a NaBH4/ZnCl2-catalyzed diastereoselective reduction
A practical asymmetric synthesis of sitagliptin phosphate, from 1-{3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo-[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl) butane-1,3-dione, in overall 65.3% yield has been reported. The target compound was synth
Pan, Xianhua,Wang, Kun,Yu, Wansheng,Zhang, Ruimin,Xu, Lu,Liu, Feng
p. 1170 - 1172
(2015/09/22)

Practical, asymmetric route to sitagliptin and derivatives: Development and origin of diastereoselectivity
The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S=O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.
Gutierrez, Osvaldo,Metil, Dattatray,Dwivedi, Namrata,Gudimalla, Nagaraju,Chandrashekar,Dahanukar, Vilas H.,Bhattacharya, Apurba,Bandichhor, Rakeshwar,Kozlowski, Marisa C.
supporting information
p. 1742 - 1745
(2015/04/14)

PROCESS FOR THE PREPARATION OF SITAGLIPTIN PHOSPHATE
The present invention relates to a method for the preparation of sitagliptin phosphate and sitagliptin phosphate anhydrous of Formula (I′) and monohydrate of Formula (I),
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Paragraph 0115-0117; 0118-0120

(2015/03/31)

PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND NOVEL INTERMEDIATES
The present invention provides an improved process for the preparation of β-amino acid derivatives. More particularly, the present invention relates to an improved process for the preparation of Sitagliptin or its pharmaceutically acceptable salts of formula 1. The present invention also provides novel intermediates used in the preparation of Sitagliptin.
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Page/Page column 18

(2015/11/10)

SITAGLIPTIN LIPOATE SALT, PROCESS FOR THE PREPARATION AND PHARMACEUTICAL COMPOSITION THEREOF
The present invention relates to Sitagliptin lipoate salt and its polymorphic forms, a process for its preparation. The present invention also relates to a pharmaceutical composition using the Sitagliptin lipoate and its polymorphic forms.
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Page/Page column 19

(2015/01/16)

PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND INTERMEDIATE COMPOUNDS
There is provided a process for the preparation of sitagliptin or a pharmaceutically acceptable salt thereof, and a process for the preparation of intermediate compounds useful in the preparation of sitagliptin. In particular, there is provided a process comprising condensing 3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)butyric acid of formula (II) with 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine of formula (III) or a salt thereof in presence of a catalyst to obtain (R)-tert-butyl-4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]-triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-yl-carbamate of formula (IV) or a pharmaceutically acceptable salt thereof. The catalyst is represented by the compound of formula (V). Compound of formula (IV) or its pharmaceutically acceptable salt obtained may be deprotected to obtain a compound of formula (I).
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Paragraph 0067; 0068; 0069; 0070

(2015/07/22)

Efficient stereocontrolled synthesis of sitagliptin phosphate
The synthesis of sitagliptin phosphate 1, a novel DPP-IV inhibitor for the treatment of type 2 diabetes mellitus has been accomplished starting from the chiral synthon (1,4-bis[(R)-1-phenylethyl]piperazine-2,5-dione) 2, involving highly stereocontrolled (>98%) alkylation as a key step, in a good overall yield of 50% over six steps.
Subbaiah,Haq, Wahajul
p. 1026 - 1030
(2014/08/18)

PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND INTERMEDIATE COMPOUNDS
There is provided a process for the preparation of sitagliptin or a pharmaceutically acceptable salt thereof, and a process for the preparation of intermediate compounds useful in the preparation of sitagliptin. In particular, there is provided a process comprising condensing 3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl) butyric acid of formula (II) with 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[l,2,4]triazolo[4,3-a] pyrazine of formula (III) or a salt thereof in presence of a catalyst to obtain (R)-tert-butyl-4-oxo-4-(3- (trifluoromethyl)-5,6-dihydro-[ 1,2,4]-triazolo[4,3-a]pyrazin-7(8H)-yl)- 1 -(2,4,5- trifluorophenyl)butan-2-yl-carbamate of formula (IV) or a pharmaceutically acceptable salt thereof. The catalyst is represented by the compound of formula (V). Compound of formula (IV) or its pharmaceutically acceptable salt obtained may be deprotected to obtain a compound of formula (I).
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Page/Page column 18

(2014/03/21)

PROCESSES FOR THE PREPARATION OF CHIRAL BETA AMINO ACID DERIVATIVES USING ASYMMETRIC HYDROGENATION CATALYSTS
This invention provides processes for the preparation of Sitagliptin and pharmaceutically acceptable salts thereof, said processes comprising enantioselective hydrogenation of a prochiral enamine using chiral ruthenium catalyst.
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Page/Page column 18

(2014/08/07)

INTERMEDIATES OF SITAGLIPTIN AND PREPARATION PROCESS THEREOF
Disclosed are intermediates of Sitagliptin, a preparation process thereof, and a process for synthesizing Sitagliptin using these intermediates. Sitagliptin is synthesized by using chiral amino compounds as a raw material, without having to build a chiral center with a chiral asymmetric catalytic hydrogenation, and high-pressure hydrogenation is avoided.
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(2013/10/22)

INTERMEDIATES OF SITAGLIPTIN AND PREPARATION PROCESS THEREOF
Disclosed are intermediates of Sitagliptin, a preparation process thereof, and a process for synthesizing Sitagliptin using these intermediates. Sitagliptin is synthesized by using chiral amino compounds as a raw material, without having to build a chiral center with a chiral asymmetric catalytic hydrogenation, and high-pressure hydrogenation is avoided.
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(2013/11/05)

PROCESSES FOR PREPARING 4-OXO-4-[3-(TRIFLUOROMETHYL)-5,6- DIHYDRO [L,2,41-TRIAZOLO[43-A]PYRAZIN-7(8H)-YL]-L-(2,4,5- TRIFLUOROPHENYL)BUTAN-2-AMINE
The present invention relates to synthesis of 4-oxo-4-[3-(trifluoromethyl)-5,6- dihydro [l,2,4]-triazolo[4,3-a]pyrazin-7(8H)-yl]-l-(2,4,5-trifluorophenyl)butan-2- amine of Formula (I) either in its racemic (R/S) form or any of its optically active (S) or (R) forms or enantiomeric excess mixture of any of the forms by novel processes. The invention further relates to certain novel intermediates useful in the preparation of compound of Formula (I) and processes for their preparation.
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(2013/05/22)

SITAGLIPTIN, SALTS AND POLYMORPHS THEREOF
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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(2013/06/28)

Efficient synthesis of sitagliptin phosphate, a novel DPP-IV inhibitor, via a chiral aziridine intermediate
Sitagliptin phosphate, a novel DPP-IV inhibitor of T2DM, has been synthesized via 12 linear steps, in an overall yield of 26%. The key step is the coupling reaction of 2,4,5-trifluorophenylmagnesium bromide with a chiral aziridine derivative, which was prepared from l-homo-serine by simple steps.
Pan, Xianhua,Li, Xiaojun,Lu, Qingling,Yu, Wansheng,Li, Weijin,Zhang, Qunhui,Deng, Fei,Liu, Feng
p. 6807 - 6809
(2013/11/19)

A NOVEL PROCESS FOR THE PREPARATION OF SITAGLIPTIN
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.
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(2013/08/15)

Asymmetric synthesis of (-)-(R)-sitagliptin
The asymmetric synthesis of (-)-(R)-sitagliptin was achieved in seven steps from commercially available starting materials using the highly diastereoselective conjugate additions of either lithium (R)-N-benzyl-N- (α-methylbenzyl)amide or lithium (R)-N-benzyl-N-(α-methyl-p- methoxybenzyl)amide to tert-butyl 4-(2′,4′,5′-trifluorophenyl) but-2-enoate to install the correct stereochemistry. Subsequent sequential acid-catalysed hydrolysis of the resultant β-amino esters, HOBt/EDC mediated coupling with the triazolopyrazine fragment, and hydrogenolysis gave (-)-(R)-sitagliptin in 43% and 42% overall yields, respectively.
Davies, Stephen G.,Fletcher, Ai M.,Lv, Linlu,Roberts, Paul M.,Thomson, James E.
p. 3052 - 3055
(2012/08/08)

PROCESSES FOR THE PREPARATION OF R-SITAGLIPTIN AND INTERMEDIATES THEREOF
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 32-33

(2012/04/17)

SITAGLIPTIN, SALTS AND POLYMORPHS THEREOF
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 33-34

(2012/03/26)

PROCESS FOR THE PREPARATION OF CHIRAL BETA AMINO CARBOXAMIDE DERIVATIVES
The present invention provides a process for preparing a compound of formula (I), or a pharmaceutically acceptable salt thereof, having the R-configuration, of formula (IA), or S-configuration of formula (IB), selectively over the other enantiomer.
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(2011/11/13)

METHOD FOR PREPARING SITAGLIPTIN AND AMINE SALT INTERMEDIATES USED THEREIN
The present invention relates to a method for preparing sitagliptin by using an amine salt of (3R)-3-azido-4-(2,4,5-trifluorophenyl)-butyric acid (formula (V)) in a high yield and purity, and amine salt intermediates used therein.
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(2011/09/19)

A novel synthetic approach to ?-aminobutyryl substituted compounds
The present invention relates to process to prepare β-aminobutyryl compounds of formula (I) wherein Q is N, CH, C-CF3 or C-phenyl, preferably N, and R10 is H, C1-C4-alkyl or fluorinated C1-C2-alkyl, preferably trifluoromethyl, and wherein X is halogen selected from fluoro, chloro, or bromo, preferably fluoro, same or different, and n is 1-4.
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Page/Page column 36-37

(2011/12/14)

PROCESS FOR PREPARATION OF (2R)-4-OXO-4-[3- (TRIFLUOROMETHYL)-5,6-DIHYDRO [1,2,4]-TRIAZOLO[4,3-A]PYRAZIN- 7(8H)-YL]-L-(2,4,5-TRIFLUOROPHENYL)BUTAN-2-AMINE and NEW IMPURITIES IN PREPARATION THEREOF
The present invention relates to synthesis of β-amino acid derivatives of formula (I) and its salts of formula (Ia) by a novel process. The process comprises the reduction of a protected or unprotected prochiral β-amino acrylic acid or derivative there of, by using borane containing reducing agents at atmospheric pressure. The resulting racemic β-amino compound is resolved to a pure stereoisomer of formula (I), specifically to (2R)-4-oxo-4-[3-Ctrifluoromethyl)-5,6-dihydrol[1,2,4]triazolo[4,3-alpyrazin-7(8H)-yl]-1-(2,4,4-trifluorophenyl)butan-2-amine. In an embodiment the invention disclosed polymorphic forms of formula (I), phosphate salt of formula (I) and also a Dibenzoyl-L-tartaric acid salt of formula (I).
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(2011/09/20)

Process for the synthesis of beta-amino acids and derivatives thereof
The present invention relates to a process for the preparation of β-amino acids and derivatives thereof, which is especially suited for gliptins and particularly sitagliptin. A key step makes use of suitably derivatized epoxides or aziridines, which owing to a chirality provides a source of chirality for intermediates which are suitable for building up β-amino acids and similar compounds, in particular in the construction of the sitagliptin molecule.
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(2012/01/06)

A NOVEL SYNTHETIC APPROACH TO ?-AMINOBUTYRYL SUBSTITUTED COMPOUNDS
The present invention relates to process to prepare β-aminobutyryl compounds of formula (I), wherein Q is N, CH, C-CF3 or C-phenyl, preferably N, and R10 is H, C1-C4-alkyl or fluorinated C1C2-alkyl, preferably trifluoromethyl, and wherein X is halogen selected from fluoro, chloro, or bromo, preferably fluoro, same or different, and n is 1-4.
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Page/Page column 43

(2011/12/14)

METHOD OF PREPARING SITAGLIPTIN
The solution relates to a method of preparing sitagliptin of formula I, comprising hydrogenation of an enamino-amide precursor of formula II, wherein the hydrogenation is carried out in a suspension or a solution and is catalyzed by a complex compound formed of Ru and an (R) or (S)-pseudo-o-bisphosphino-[2,2]-paracyclophane ligand of general formula VI, wherein R are the same or different substituents from the group consisting of C1-4 alkyls, C3-8 cycloalkyls and Ar, and Ar is an unsubstituted or substituted aryl, and optionally other component(s) necessary for formation of the complex compound.
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(2011/10/10)

PREPARATION OF SITAGLIPTIN AND SALTS THEREOF
Processes for preparing sitagliptin and its pharmaceutically acceptable salts, and process intermediates.
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Page/Page column 21-22

(2011/04/14)

IMPROVED PROCESS FOR PREPARATION OF (2R)-4-OXO-4-[3- (TRIFLUOROMETHYL)-5,6-DIHYDRO [1,2,4]-TRIAZOLO[4,3-A]PYRAZIN- 7(8H)-YL]-L-(2,4,5-TRIFLUOROPHENYL)BUTAN-2-AMINE and NEW IMPURITIES IN PREPARATION THEREOF
The present invention relates to synthesis of β-amino acid derivatives of formula (I) and its salts of formula (Ia) by a novel process. The process comprises the reduction of a protected or unprotected prochiral β-amino acrylic acid or derivative there of, by using borane containing reducing agents at atmospheric pressure. The resulting racemic β-amino compound is resolved to a pure stereoisomer of formula (I), specifically to (2R)-4-oxo-4- [3-Ctrifluoromethyl)-5, 6-dihydrol [1,2,4]triazolo [4,3-alpyrazin-7(8H)-yl]-1-(2,4,4-trifluorophenyl)butan-2-amine. In an embodiment the invention disclosed polymorphic forms of formula (I), phosphate salt of formula (I) and also a Dibenzoyl-L-tartaric acid salt of formula (I).
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Page/Page column 54

(2010/04/25)

PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND ITS INTERMEDIATES
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 54

(2010/11/05)

The asymmetric synthesis of Sitagliptin, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
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.
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)

CRYSTALLINE SALTS OF SITAGLIPTIN
The present invention relates to crystalline monobasic, dibasic and tribasic acid addition salts of the dipeptidyl peptidase-IV inhibitor sitagliptin.
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Page/Page column 19-20

(2010/04/03)

NOVEL CRYSTALLINE POLYMORPH OF SITAGLIPTIN DIHYDROGEN PHOSPHATE
The present invention relates to a novel anhydrous crystalline form of sitagliptin dihydrogenphosphate (I), to processes for its preparation and to its use in pharmaceutical compositions.
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Page/Page column 14

(2010/12/17)

PROCESS FOR THE PREPARATION OF R-SITAGLIPTIN AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
The present invention provides processes for the preparation of R-sitagliptin and its pharmaceutically acceptable salts thereof.
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Page/Page column 12

(2010/12/29)

CRYSTALLINE FORMS OF SITAGLIPTIN PHOSPHATE
A Sitagliptin phosphate characterized by data selected from the group consisting of: a powder XRD pattern with peaks at 4.7, 13.5, 17.7, 18.3, and 23.7 ±0.2 degrees two theta; a powder XRD pattern with peaks at about 4.7, 13.5, and 15.5 ±0.2 degrees two theta and at least another two peaks selected from the following list: 14.0, 14.4, 18.3, 19.2, 19.5 and 23.7 ±0.2 degrees two theta; and a powder XRD pattern with peaks at about 13.5, 19.2, and 19.5 ±0.2 degrees two theta and at least another two peaks selected from the following list: 4.7, 14.0, 15.1, 15.5, 18.3, and 18.7 ±0.2 degrees two theta; a powder XRD pattern with peaks at about 13.5, 15.5, 19.2, 23.7, and 24.4 ±0.2 degrees two theta; and a powder XRD pattern with peaks at about 4.65, 13.46, 17.63, 18.30, and 23.66 ±0.10 degrees two theta, processes for preparing said Sitagliptin crystalline form, and pharmaceutical compositions thereof, are provided.
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Page/Page column 43

(2009/10/22)