1044676-63-2

Upstream product

• 702-82-9 3-aminoadamantan-1-ol 
• 207557-35-5 (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile 
• 768-94-5 1-Adamantanamine 
• 665-66-7 amantadine hydrochloride 
• 23500-10-9 (S)-1-(2-chloroacetyl)pyrrolidine-2-carboxylic acid 
• 1334337-69-7 [(3-hydroxyadamantan-1-yl)imino]acetic acid 
• 924281-70-9 t-butyl 2-(adamantan-1-ylamino)acetate 
• 1334337-68-6 t-butyl 2-(3-hydroxyadamantan-1-ylamino)acetate 
• 35150-07-3 (S)-tert-butyl 2-carbamoylpyrrolidine-1-carboxylate 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 147-85-3 L-proline 
• 204387-53-1 (2S)-pyrrolidine-2-carbonitrile 
• 1032564-18-3 [(3‐hydroxytricyclo[3.3.1.13,7]decan‐1‐yl)amino]acetic acid 
• 584-08-7 potassium carbonate 

Downstream Products

• 1147403-03-9 NVP-BQS867-NX-2 
• 565453-39-6 vildagliptinamide 
• 1789703-37-2 2-(3-hydroxyadamantan-1-yl)-1-imino-hexahydropyrrolo[1,2-a]pyrazin-4-one 
• 565453-40-9 vildagliptin carboxylic acid 

Relevant academic research and scientific papers

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%.

Synthesis of vildagliptin utilizing continuous flow and batch technologies

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.

An economical and facile method to synthesize vildagliptin

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.

Novel synthesis of heterocycle-containing adamantane derivatives

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.

PROCESS FOR THE PREPARATION OF VILDAGLIPTIN

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.

Continuous preparation method of vildagliptin

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.

Production method of vildagliptin

and Alkali metal bromides are in vildagliptin or a salt thereof. Use of a crystal form, a deuterated substance, a tritium substitute, and a solvate as a catalyst. The vildagliptin product produced by the method is high in purity and low in impurity content, particularly the product quality control of the vildagliptin bulk drug and/or the pharmaceutical preparation is facilitated. Moreover, the reaction condition is mild, operation and control are convenient, the yield is high, the energy consumption is low, the cost is low, and the method is suitable for industrial production and popularization and application.

Synthesis method of vildagliptin

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.

Cerium-Catalyzed C-H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents

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.

Synthetic method of vildagliptin

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.