- A facile method to synthesize vildagliptin
-
An efficient and high-yielding synthetic method for the preparation of vildagliptin via four steps is reported. The process starts from L-proline and involves a successful reaction with chloroacetyl chloride in tetrahydrofuran to afford (S)-1-(2-chloroacetyl)pyrrolidine-2-carboxylic acid, followed by a reaction with acetonitrile in the presence of sulfuric acid to give (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile. This is then reacted with 3-aminoadamantanol to give vildagliptin. 3-Aminoadamantanol is prepared from 1-aminoadamantane hydrochloride via oxidation with sulfuric acid/nitric acid and boric acid as the catalyst followed by ethanol extraction. The overall yield is 95%.
- Zhang, Li,Jiang, Lan,Guan, Xiaoshu,Cai, Linhong,Wang, Jingyu,Xiang, Peng,Pan, Junyi,Hu, Xiangnan
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p. 305 - 309
(2020/12/01)
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- Continuous preparation method of vildagliptin
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The invention discloses a continuous preparation method of vildagliptin, which comprises the following steps: 1, preparing (S)-1-(2-chloracetyl) pyrrolidine-2-carbonitrile from (S)-pyrrolidine-2-carbonitrile p-toluenesulfonate, chloroacetyl chloride, triethylamine and dichloromethane, washing, separating the liquid, and keeping the organic phase; 2, adding water and 3-amino-1-adamantanol into the organic phase, refluxing, evaporating to remove the organic solvent, heating, and reacting to obtain a feed liquid; 3, washing the feed liquid, cooling, adjusting to be acidic, and washing to obtain feed liquid; and 4, carrying out aqueous phase extraction, cooling, adjusting to alkalinity, carrying out liquid separation to reserve an organic phase, carrying out aqueous phase re-extraction, carrying out liquid separation, merging the organic phases, evaporating to remove the solvent, and adding a crystallization solvent to obtain vildagliptin with HPLC purity of 99.5% or more. The raw material provided by the invention is low in water absorption and convenient to prepare, store and feed; through continuous process operation, the operation steps are reduced, and the overall yield is improved; finally, water is used as a reaction solvent, so that the production cost is reduced, the environmental pollution pressure is reduced, and the method is suitable for preparing vildagliptin.
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Paragraph 0034-0046
(2021/04/21)
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- PROCESS FOR THE PREPARATION OF VILDAGLIPTIN
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The present invention relates to process for the preparation of Vildagliptin. The present invention involves an ecologically friendly process by avoiding the dehydrating agent and use of reagents that are less expensive, easier to handle and its cost effective industrial applicable process.
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Page/Page column 8
(2021/06/22)
-
- Cerium-Catalyzed C-H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents
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Modern photoredox catalysis has traditionally relied upon metal-to-ligand charge-transfer (MLCT) excitation of metal polypyridyl complexes for the utilization of light energy for the activation of organic substrates. Here, we demonstrate the catalytic application of ligand-to-metal charge-transfer (LMCT) excitation of cerium alkoxide complexes for the facile activation of alkanes utilizing abundant and inexpensive cerium trichloride as the catalyst. As demonstrated by cerium-catalyzed C-H amination and the alkylation of hydrocarbons, this reaction manifold has enabled the facile use of abundant alcohols as practical and selective hydrogen atom transfer (HAT) agents via the direct access of energetically challenging alkoxy radicals. Furthermore, the LMCT excitation event has been investigated through a series of spectroscopic experiments, revealing a rapid bond homolysis process and an effective production of alkoxy radicals, collectively ruling out the LMCT/homolysis event as the rate-determining step of this C-H functionalization.
- An, Qing,Chen, Yuegang,Liu, Weimin,Pan, Hui,Wang, Xin,Wang, Ziyu,Zhang, Kaining,Zuo, Zhiwei
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p. 6216 - 6226
(2020/04/27)
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- Synthesis method of vildagliptin
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The invention discloses a synthesis method of vildagliptin. The method comprises the following steps: performing esterification reaction on L-glutamic acid and ethanol to obtain L-glutamic acid-gamma-ethyl ester; reducing the L-glutamic acid-gamma-ethyl ester under the action of potassium borohydride to obtain L-proline; mixing L-proline with ethyl chloroformate for reaction to obtain acid anhydride; further reacting the acid anhydride with amine to obtain amide; dehydrating the amide under the action of phosphorus pentoxide to obtain an intermediate 1; performing substitution reaction on theintermediate 1 and chloroacetyl chloride to obtain an intermediate 2; and further reacting the intermediate 2 with 3-amino-1-adamantanol to obtain vildagliptin. The method has the advantages that fewimpurities are generated in the vildagliptin preparation process, the yield of the prepared vildagliptin is high, and compared with the prior art, the process is simpler, and the vildagliptin preparation cost is greatly reduced.
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-
-
- Preparation method of vildagliptin
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The invention relates to a preparation method of vildagliptin. The preparation method comprises the following steps: (1) adding 1,1,1,3,3,3-hexamethyldisilazane, 3-aminoadamantanol, a catalyst and dichloromethane into a reactor, carrying out heating, carrying out a heat-preserved reaction, and after the reaction is completed, evaporating out 1,1,1,3,3,3-hexamethyldisilazane and the solvent to obtain a silicyl-protected 3-aminoadamantanol crude product; and (2) adding potassium iodide, organic alkali and acetonitrile into the reactor filled with the silicyl-protected 3-aminoadamantanol crude product, carrying out heating, dropwise adding (S)-1-(2-chloroacetyl chloride)pyrrolidine-2-carbonitrile dissolved in acetonitrile, carrying out a reaction for 1-6 h, adding ethanol with a concentrationof 95%, continuing stirring for 0.5-2 h, and successively performing cooling, filtering, desolventizing and recrystallizing after the stirring reaction is finished so as to obtain vildagliptin. The preparation method can significantly reduce the generation of the impurity Ia, improve yield and reduce the cost, and is beneficial for industrial production.
- -
-
Paragraph 0039; 0042-0044; 0047-0049; 0052-0053
(2020/01/12)
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- Synthetic method of vildagliptin
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The invention discloses a synthetic method of vildagliptin. Glycolic acid and (S)-pyrrolidine-2-carbonitrile are used as raw materials; a condensation reaction is carried out under the action of a condensing agent, so that (S)-1-(2-hydroxyacetyl) pyrrolidine-2-formonitrile is prepared; and then the (S)-1-(2-hydroxyacetyl) pyrrolidine-2-carbonitrile and thionyl chloride are subjected to a substitution reaction, wherein only reduced pressure distillation is needed to remove small molecular compounds to obtain a relatively pure carbon tetrachloride solution containing (S)-1-(2-chloracetyl) pyrrolidine-2-carbonitrile; finally, 3-amino-1-adamantanol hydrate and cesium carbonate are added into the solution, and a substitution reaction is carried out just in 4-5 h, finally, the purity of a crudeproduct reaches up to 99.85% after ethyl alcohol recrystallization. According to the present invention, a high-efficiency synthesis route is provided for synthesis of high-purity vildagliptin, and good practicability is achieved.
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-
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- Preparation method for vildagliptin
-
The invention provides a preparation method for vildagliptin. Through the presence of imidazo thiazole as a chiral ligand and a palladium catalyst, a vildagliptin product with high yield and high purity can be obtained by taking diethyl fumarate and amino protected (S)-3-amino-cyano-ethyl propanoate as initial raw materials through steps such as cyclization, deprotection and coupling; and the preparation method is short in reaction route, high in yield and less in by-product, so that production costs can be reduced, and industrial production can be realized.
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- Synthesizing method of vildagliptin
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The invention discloses a synthesizing method of vildagliptin, and belongs to the field of medicine intermediate synthesis. The method includes the steps of conducting an imidization with 3-amino-1-adamantanol and monohydrated glyoxylic acid as the raw materials to obtain (3-hydroxyl adamantly imino)acetic acid, conducting acylation condensation on the (3-hydroxyl adamantly imino)acetic acid and (S)-pyrrolidine-2-formonitrile under the catalysis of electron-withdrawing phenylboric acid to obtain (2S)-1-[[(3-hydroxyl tricyclic[3,3,1,1[3,7]]decane-1-yl)imino]acetyl]pyrrolidine-2-formonitrile, and then conducting hydrazine hydrate reduction to obtain vildagliptin. A one-pot method is adopted, operation is simple, impurities are few, the product is easy to purify, the purifying steps are reduced, cost is reduced, and the method is suitable for industrial production.
- -
-
Paragraph 0016; 0047; 0049; 0050-0052; 0053; 0055
(2018/10/04)
-
- Method for preparing vitaletine
-
The invention discloses a method for preparing vitaletine, and belongs to the field of synthesizing of medicine intermediates. The method comprises the following steps of using 3-amino-1-amantadol andmonohydrated acetaldehyde acid as raw materials, and performing imidization reaction, so as to obtain (3-hdyroxyl amantadine)acetic acid; under the catalyzing function of tris(2,2,2-trifluoroethyl)borate, acylating and condensing with (S)-pyrrolidine-2-formonitrile, so as to obtain (2S)-1-[[(3-hydroxyl tricyclic[3.3.1.1[3,7]]decane-1-yl)imino]acetyl]pyrrolidine-2-formonitrile; reducing by palladium carbon/ammonium formate, so as to obtain the vitaletine. The method has the advantages that one-pot process is adopted, the operation is simple, fewer impurities are contained, the product is easyto purify, the purifying step is not needed, the cost is reduced, and the method is suitable for industrialized production.
- -
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Paragraph 0049; 0052; 0053; 0054; 0055
(2018/11/03)
-
- Synthetic method of vildagliptin
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The invention relates to the technical field of drug synthesis and particularly relates to a synthetic method of vildagliptin. The synthetic method comprises the following steps: carrying out imino group protection and acylamino dehydration on a starting raw material, namely L-prolinamide, and carrying out deproteciton salification by virtue of p-toluene sulfonic acid so as to obtain p-toluenesulfonate of (S)-2-cyanopyrrolidine; substituting and hydrolyzing 3-amino-1-adamantanol so as to obtain 3-iminoacetic acid-1-adamantanol; carrying out condensation acylation by virtue of 3-iminoacetic acid-1-adamantanol and (S)-2-cyanopyrrolidine under the action of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, so as to obtain the vildagliptin. The synthetic method has the beneficial effects that reaction conditions are mild, an intermediate does not absorb moisture and is easy to store, the purity of the synthesized vildagliptin is high and is more than or equal to 99.50%, and the maximum single impurity content is less than or equal to 0.10%.
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- 2 - substituted pyrrolidines compound, preparation method and its application in the preparation of the peculiar smell (by machine translation)
-
The invention discloses a 2 - substituted pyrrolidines compound, preparation method and its application in the preparation of the peculiar smell, the tetrahydro-pyrrole derivatives of formula (I) has the structure as illustrated, using the intermediate synthesis when the peculiar smell, the preparation method of the original source of auxiliary materials are cheap and easily obtained, the process route is short, low cost, mild conditions in the reaction process of the security, without the special requirements of the device, can be suitable for industrial production. (by machine translation)
- -
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Paragraph 0007; 0062; 0069; 0070
(2017/08/25)
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- A high efficient synthesis method of vergeliptin
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The present invention relates to an efficient synthesis method of vildagliptin. According to the method, L-prolinamide is adopted as a raw material, N-chloro acetylation and amide dehydration are performed to generate an intermediate (S)-1-(2-chloroacetyl chloride)pyrrolidine-2-carbonitrile, and the (S)-1-(2-chloroacetyl chloride)pyrrolidine-2-carbonitrile and 3-amino adamantanol are subjected to condensation in acetonitrile in the presence of an organic base to obtain the target product vildagliptin. According to the present invention, the synthesis method operation only requires the separation of the one key intermediate, and the method has characteristics of simple and feasible operation, high efficiency, environmental protection, and easy industrial production achieving.
- -
-
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- Preparation method for Vildagliptin
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The invention relates to a preparation method for Vildagliptin. The preparation method comprises the following steps: using L-prolinamide as a raw material, performing the dehydration reaction with cyanuric chloride, and generating (S)-2-cyanopyrrolidine; performing the salt forming reaction to the (S)-2-cyanopyrrolidine and hydrogen chloride, to obtain intermediate-1; enabling the intermediate-1 to react with chloroacetic acid under the conditions of using EDCI as a condensing agent, using HOBt as a catalyst, and using DIEA as an acid-binding agent, to obtain intermediate-2; enabling the intermediate-2 to react with 3-amino-1-adamantanol, to obtain the Vildagliptin, filtering, concentrating, crystallizing, and re-filtering to obtain a Vildagliptin crude product; and preparing the Vildagliptin finished product by the acetone refining. The preparation method is capable of providing a new method, and reducing the generation of by-products in each step. The content of the disubstitution product of the Vildagliptin by-product and the 3-amino-1-adamantanol are reduced to less than 0.1%, the yield and purity of the Vildagliptin are effectively improved, the raw materials are easily obtained, the conditions are moderate, and the preparation method is suitable for the industrial large-scale production.
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- Method of preparing Vida row sandbank
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The invention discloses a preparation method of vildagliptin, and the preparation method comprises the following steps: 1) in the presence of a first solvent and a reducing agent, a formula II compound reacts with a formula III compound to obtain a formula IV compound; 2) in the presence of a second solvent, an alkali and a halide, the formula IV compound reacts with a formula V compound to obtain a formula VI compound; and 3); in the presence of a third solvent, the vildagliptin is obtained by debenzylation of the formula VI compound. The preparation method avoids generation of bi-substituted and other by-products of synthesis methods in the prior art, has the advantages of simple operation and low cost, and is suitable for industrial production.
- -
-
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- Preparation method of vildagliptin
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The invention discloses a preparation method of vildagliptin; a non-homogeneous system with acetonitrile as a main solvent and potassium carbonate and iodine salt as main components is used, two key fragments of (S)-1-(2-chloroacetyl chloride)-2-nitrile pyrrolidine and 3-amino-1-adamantanol are coupled to prepare vildagliptin, and the intermediate conversion rate and the yield are both superior to those of the prior art; the preparation method adopts iodine ion salt for activating chlorine in a reactant structure, and a phase transfer catalyst is selected to be added for promoting the effect of a non-homogeneous reaction.
- -
-
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- Method for preparing substituted (S)-pyrrolidine-2-formonitrile and vildagliptin
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The invention provides a method for preparing (S)-1-(2-halogenated acetyl)pyrrolidine-2-formonitrile as shown in the formula (I). Optionally in the presence of a diluent, (S)-1-(2-halogenated acetyl)pyrrolidine-2-formamide and a dehydrating agent propanephosphonic acid cyclic anhydride (T3P) react with each other. The invention also provides a method for preparing vildagliptin by using S-prolinamide involving the above reaction. The method for preparing the compound as shown in the formula (I) has the following advantages: use of expensive trifluoroacetic anhydride is not required, yield is increased, and cost is reduced; use of cyanuric chloride prepared from highly toxic raw materials is not required, and the reaction is more environmentally friendly; and an improved method for preparing vildagliptin is then obtained. In the formula (I) and formula (II), X1 is halogen.
- -
-
-
- A process for the purification of sandbank thickuygur Geleg
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The invention relates to a purification method of a vildagliptin crude product, which is characterized by comprising the following steps: adding a vildagliptin crude product obtained by reacting (S)-1-(2-chloracetyl)pyrryl-2-formonitrile and 3-amino-1-adamantanol disclosed as Formula (II) into a solvent to form a reaction mother solution, adding silica gel into the reaction mother solution, and stirring uniformly at 30-40 DEG C, wherein the solvent is any one of aromatic hydrocarbons, hydrochloric ethers, C1-C5 carboxylates, ketones and alcohols, and the weight ratio of the silica gel to the (S)-1-(2-chloracetyl)pyrryl-2-formonitrile is 0.5:1-6:1; filtering to obtain a filtrate; and finally, recrystallizing to obtain the vildagliptin pure product disclosed as Formula (I), wherein the content of the 3-amino-1-adamantanol raw material disclosed as Formula (II) in the vildagliptin pure product is lower than 0.05%. The purification method can lower the content of the impurity disclosed as Formula (II) to 0.05%, has satisfactory yield, and can implement large-scale application in industry.
- -
-
Paragraph 0031-0032
(2017/02/09)
-
- Preparing method for vildagliptin
-
The invention relates to a preparing method for vildagliptin and belongs to the field of compound preparation. The method comprises the following steps that under an amide organic solvent system and the existence of alkali, 3-amino-1-adamantanol and (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile are subjected to an alkylation reaction, and a reaction solution is obtained; then, the reaction solution is subjected to posttreatment, and vildagliptin is obtained. The method has the advantages that reaction raw materials and a solvent are saved, the yield is high, purity is high, the content of dipolymer impurities is low, the medicinal requirement is met, operation is simple, the reaction time is short, posttreatment is easy, and industrialization is promoted.
- -
-
Paragraph 0068; 0069; 0070; 0071; 0072; 0073
(2017/02/23)
-
- NOVEL ECONOMIC PROCESS FOR VILDAGLIPTIN
-
The present invention relates to a commercially viable novel process for manufacturing Vildagliptin in high yield with high chemical and chiral purity.
- -
-
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- AN ADVANCED AND COST-EFFECTIVE PROCESS FOR PREPARING HIGHLY PURE VILDAGLIPTIN
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The present invention describes an improved process for preparing highly pure (S)-1-[N- (3-hydroxy-l-adamantyl) glycyl] pyrrolidine-2-carbonitrile known as Vildagliptin. Also the present invention discloses a novel insitu process for preparing an intermediate (2S)- l-(chloroacetyl)pyrrolidine-2-carbonitrile. Further, the present invention discloses a method of preparing undesired dimer impurity.
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- Synthesis of vildagliptin utilizing continuous flow and batch technologies
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The preparation and utilization of the Vilsmeier reagent (VR) is well-known in the literature with its usefulness and scope being frequently demonstrated in organic synthesis. However, it is an irritant and has a high thermal energy of decomposition; consequently, these factors lead to operational issues on larger scale which suggests approaches whereby the reagent is not isolated. Herein, we report the in-line formation and instantaneous consumption of VR utilizing both conventional batch and flow technologies. The approach is demonstrated by way of the synthesis of Vildagliptin, thereby mitigating potential safety and hygiene hazards.
- Pellegatti, Laurent,Sedelmeier, Jorg
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p. 551 - 554
(2015/04/27)
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- AN IMPROVED PROCESS FOR PREPARING VILDAGLIPTIN
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The present invention relates to efficient, environment friendly and economical processes for the preparation of vildagliptin without isolating the intermediate compounds. Also provided is a process for the recovery of expensive 1-aminoadamantane-3-ol and use thereof in the preparation of vildagliptin.
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-
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- A facile and economical method to synthesize vildagliptin
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A mild and economical method to prepare vildagliptin had been reported with a good yield. In this paper, vildagliptin was synthesized from L-proline and 3-amino-1-adamantanol through chloride acetylation, amination, dehydration and substitution. The total yield of the target compound was 59%.
- Deng, Yu,Wang, Anmin,Tao, Zhu,Chen, Yingjie,Pan, Xinmei,Hu, Xiangnan
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p. 780 - 784
(2015/04/14)
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- An economical and facile method to synthesize vildagliptin
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A facile and economical synthefic method to prepare vildagliption with-reported.It was started from L proline via succsessful reaction with chloried in tetrahydrofuran to-afford 1(2-chloroacetyl) pyrrolidine-2-carboxylic-acid, followed by reacting with 2-chloro-46-dimethoxy-1,3,5-triazine,N-methylmorpholine and 2,4,6-triazine,N-methlmorpholine-2,4,6-trichloro-1,3,5-triazine-to-give 1-(2-chloroacetyl)-pynolidine 2-carbonitrile which was-reacfed-with 3-aminoadmantanol to get the-forget-compound-of-vildagliption.
- Deng, Yu,Wang, Anmin,Tao, Zhu,Chen, Yingjie,Pan, Xinmei,Hu, Xiangnan
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p. 6275 - 6278
(2015/02/19)
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- IMPROVED PROCESS FOR PREPARATION OF VILDAGLIPTIN INTERMEDIATE
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Provided is an improved process for preparation of Vildagliptin intermediate, 1-chloro acetyl (S)-2-cyano pyrrolidine.
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- IMPROVED PROCESS FOR PREPARATION OF VILDAGLIPTIN
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The present invention relates to process for the preparation of vildagliptin.
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- AMORPHOUS VILDAGLIPTIN
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The present invention provides a novel amorphous Form of vildagliptin, process for its preparation and pharmaceutical compositions comprising it. The present invention also provides a solid dispersion of vildagliptin in combination with a pharmaceutically acceptable carrier, process for its preparation and pharmaceutical compositions comprising it.
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Page/Page column 6; 7
(2014/02/15)
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- A PROCESS FOR THE PREPARATION OF VILDAGLIPTIN AND ITS INTERMEDIATE THEREOF
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A process for preparation of vildagliptin is discussed wherein 3-amino-1- adamantanol is reacted with 1-chloroacetyl(S)-2-cyanopyrrolidine in solvent and base to obtain vildagliptin. This invention also relates to a process for preparation of 1-chloroacetyl(S)-2-cyanopyrrolidine, a vildagliptin intermediate is provided. Further, the present invention also provides a co- precipitate of amorphous form of vildagliptin along with pharmaceutically acceptable excipients.
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Page/Page column 39; 40
(2014/01/07)
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- Novel synthesis of heterocycle-containing adamantane derivatives
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A novel approach to synthesize the of heterocycle-containing adamantane derivatives 1-{[(3-hydroxy-1-adamantyl)amino]acetyl}-2- cyano-(S)-pyrrolidine and N-{2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl}adamantane-1-carboxamide, which were effective in treatment of diabetes and depression respectively, have been described. The target compounds were synthesized by raw materials of inexpensive L-proline and available 1-(2-pyrimidinyl) piperazine respectively. Compared with traditional synthetic routes, the method provides several advantages such as inexpensive and readily available raw materials, convenient manipulation and high yield.
- Xu, Xiaojian,Guo, Jianwei,Su, Qiang,Zhong, Xing
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p. 7557 - 7560
(2013/08/23)
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- A cost-effective method to prepare pure vildagliptin
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A cost-effective synthetic approach to prepare vildagliptin under gentle experimental conditions has been reported with good yield and high purity. It was initiated with L-proline via successful reaction with chloroacetyl chloride in THF (Tetrahydrofuran) to give the 1-(2-chloroacetyl)-pyrrolidine-2-carboxylic acid, which was then treated by TCT (2, 4, 6-trichloro-1, 3, 5-triazine) in DCM (dichloromethane), and converted into 1-(2-chloroacetyl)-pyrrolidine-2- carboxamide, then further converted into 1-(2-chloroacetyl)-pyrrolidine-2- carbonitrile after dehydrated by TCT in DMF (N, N- dimethylformamide), the latter product was reacted with 3-Aminoadamantanol to get vildagliptin. The total yield of vildagliptin was about 48%, the purity was about 99%.
- Peng, Jun,Feng, Yue,Tao, Zhu,Chen, Yingjie,Hu, Xiangnan
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p. 159 - 163
(2013/07/26)
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- NEW PROCESS AND INTERMEDIATES FOR THE SYNTHESIS OF VILDAGLIPTIN
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A new process for the synthesis of vildagliptin a via a novel intermediate formed by salification of prolinamide with haloacetic acid.
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Page/Page column 10
(2013/06/27)
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- INORGANIC SALT COMPLEXES OF VILDAGLIPTIN
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The present invention relates to the use of novel vildagliptin complexes for the manufacture of high purity vildagliptin of Formula I and/or pharmaceutical acceptable salts thereof. Further objects of the present invention are pharmaceutically acceptable complexes of vildagliptin and/or amorphous and crystalline forms, anhydrous forms, amorphous and crystalline hydrates, amorphous and crystalline solvates of the complexes and a process for the preparation thereof. Another object of the present invention is the high purity vildagliptin and pharmaceutically acceptable salts thereof prepared form the vildagliptin complexes of the present invention, a process for the preparation thereof and pharmaceutical compositions containing vildagliptin base, pharmaceutically acceptable salts and/or complexes and use thereof for the treatment of type 2 diabetes (NIDDM). The present invention provides pharmaceutically advantageous high purity vildagliptin complexes.
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Page/Page column 7
(2013/02/28)
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- PROCESS AND INTERMEDIATES FOR PREPARATION OF AN ACTIVE INGREDIENT
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A process for the synthesis of vildagliptin and intermediates useful in said process are described.
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- PROCESS FOR PREPARATION OF DPP-IV INHIBITORS
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Process for the preparation of DPP-IV inhibitors, such as 1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine are disclosed.
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-
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- INORGANIC SALT COMPLEXES OF VILDAGLIPTIN
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The present invention relates to the use of novel vildagliptin complexes for the manufacture of high purity vildagliptin of Formula I and/or pharmaceutical acceptable salts thereof. Further objects of the present invention are pharmaceutically acceptable complexes of vildagliptin and/or amorphous and crystalline forms, anhydrous forms, amorphous and crystalline hydrates, amorphous and crystalline solvates of the complexes and a process for the preparation thereof. Another object of the present invention is the high purity vildagliptin and pharmaceutically acceptable salts thereof prepared form the vildagliptin complexes of the present invention, a process for the preparation thereof and pharmaceutical compositions containing vildagliptin base, pharmaceutically acceptable salts and/or complexes and use thereof for the treatment of type 2 diabetes (NIDDM). The present invention provides pharmaceutically advantageous high purity vildagliptin complexes.
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Page/Page column 24
(2011/04/26)
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- SYNTHESIS AND USE OF VILDAGLIPTIN FOR THE PREPARATION OF PHARMACEUTICAL DOSAGE FORMS
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The present invention relates the synthesis of vildagliptin in the presence of phase transfer catalysts; as well as the use of vildagliptin or its pharmaceutically acceptable salts for the preparation of solid oral dosage forms.
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Page/Page column 44-45
(2011/02/24)
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- PROCESS FOR PREPARING VILDAGLIPTIN
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The present invention relates to a process for preparing vildagliptin of formula (I) with high chemical and enantiomeric purity and compositions comprising vildagliptin. In addition, the present invention relates to (2S,2′S)-1,1′-[[(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)imino]bis(1-oxo-2,1-ethanediyl)]di(2-pyrrolidinecarbonitrile) of formula (II), processes for preparing, and compositions comprising a compound for formula (II). Furthermore, the invention relates to processes for determining the purity of vildagliptin using a compound of formula (II).
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Page/Page column 5-6
(2008/12/06)
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- PROCESS FOR THE PREPARATION OF N-SUBSTITUTED 2-CYANOPYRROLIDINES
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The present invention relates to a process for the preparation of a N-(N'-substituted glycyl)-2-cyanopyrrolidine comprising at least (a) reacting, in the presence of dimethylformamide, a compound of formula (V) wherein, independently of each other, X1 and X3 are halogen; X2 is halogen, OH, O-C(=O)-CH2X3, -O-SO2-(C1-8)alkyl or -O-SO2-(aryl), with L-prolinamide, followed by (b) reacting the resultant compound without isolation with a dehydration agent, optionally followed by (c) reacting, in the presence of a base, the resultant compound without isolation with an appropriate amine and (d) recovering the resultant cornpound in free form or in acid addition salt form.
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- 1-[[(3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: A potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties
-
Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure - activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2-[5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)pyrrolidine (NVP-DPP728, 8c) to its follow-up, 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)pyrrolidine (NVP-LAF237, 12j). The pharmacological profile of 12j in obese Zucker fa/fa rats along with pharmacokinetic profile comparison of 8c and 12j in normal cynomolgus monkeys is discussed. The results suggest that 12j is a potent, stable, selective DPP-IV inhibitor possessing excellent oral bioavailability and potent antihyperglycemic activity with potential for once-a-day administration.
- Villhauer, Edwin B.,Brinkman, John A.,Naderi, Goli B.,Burkey, Bryan F.,Dunning, Beth E.,Prasad, Kapa,Mangold, Bonnie L.,Russell, Mary E.,Hughes, Thomas E.
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p. 2774 - 2789
(2007/10/03)
-
