207557-35-5

Basic information

• Product Name: (2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile
• Synonyms: (2S)-1-(2-Chloroacetyl)-2-9-pyrrolidinecarbonitrile;Vildagliptin interMediate C;vildagliptin Impurity J;cas:207557-35-5;2-Pyrrolidinecarbonitrile, 1-(chloroacetyl)-, (2S)-;(S)-1-(2-CHLOROACETYL)PYRROLIDINE-2-CARBONITRILE;(2S)-1-(CHLOROACETYL)-2-PYRROLIDINECARBONITRILE;(2S)-1-CHLOROACETYLPYRROLIDINE-2-CARBONITRILE
• CAS NO: 207557-35-5
• Molecular Formula: C₇H₉ClN₂O
• Molecular Weight: 172.61
• EINECS: 1592732-453-0
• Product Categories: Pharmaceuticalintermediates;ACETYLHALIDE;intermediate
• Mol File: 207557-35-5.mol

Chemical Properties

• Melting Point: 52-53 °C
• Boiling Point: 363.149 °C at 760 mmHg
• Flash Point: 173.427 °C
• Appearance: /
• Density: 1.273 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.519
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: -4.65±0.40(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: (2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: (2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile(207557-35-5)
• EPA Substance Registry System: (2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile(207557-35-5)

Safety Data

• Hazardous Substances Data: 207557-35-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile is used as a key intermediate for the synthesis of dipeptidyl peptidase IV (DPP-IV) inhibitors, specifically for the production of Vildagliptin (V305000). This application is significant because DPP-IV inhibitors play a vital role in managing type 2 diabetes by reducing blood glucose levels and improving insulin sensitivity.
As a result, (2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile is essential in the development of medications that help control and manage diabetes, offering a promising avenue for the treatment of this prevalent metabolic disorder.

InChI:InChI=1/C7H9ClN2O/c8-4-7(11)10-3-1-2-6(10)5-9/h6H,1-4H2/t6-/m0/s1

Upstream product

• 204387-54-2 (2S)-pyrrolidine-2-carbonitrile 4-methylbenzene-1-sulfonic acid 
• 79-04-9 chloroacetyl chloride 
• 204387-53-1 (2S)-pyrrolidine-2-carbonitrile 
• 79-11-8 chloroacetic acid 
• 96166-39-1 1-glycoloyl-L-proline amide 
• 228244-04-0 tert-butyl (2S)-2-cyanopyrrolidine-1-carboxylate 
• 1119-33-1 (S)-2-Amino-pentanedioic acid 5-ethyl ester 
• 56-86-0 L-glutamic acid 
• 42429-27-6 L-prolinamide hydrochloride 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 35150-07-3 (S)-tert-butyl 2-carbamoylpyrrolidine-1-carboxylate 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 23500-10-9 (S)-1-(2-chloroacetyl)pyrrolidine-2-carboxylic acid 
• 7531-52-4 L-prolinamide 

Relevant articles and documents

Synthesis of main impurity of vildagliptin

A four-step synthesis of the main impurity of vildagliptin has been easily accomplished with high-yielding starting from L-proline. This compound can be used as a reference marker in an analytical method to determine the chemical purity of the vildagliptin.

Design, synthesis, biological screening, and molecular docking studies of piperazine-derived constrained inhibitors of DPP-IV for the treatment of type 2 diabetes

Novel piperazine-derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. From a library of compounds synthesized, 1-(2-(4-(7-Chloro-4-quinolyl)piperazin-1-yl)acetyl)pyrrolidine (2g) was identified as a potential DPP-IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two-week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP-IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies.

Preparation method of high chiral purity (S)-1-(2-chloracetyl) pyrrolidine-2-formonitrile

The invention discloses a preparation method of high chiral purity (S)-1-(2-chloracetyl) pyrrolidine-2-formonitrile, the preparation method comprises: S1, in the presence of a solvent and an acid-binding agent, carrying out a coupling reaction on L-proline and chloracetyl chloride to obtain an intermediate I; s2, in the presence of a solvent and sodium iodide, carrying out cyclization reaction on the intermediate I in an alkaline environment to obtain an intermediate II; s3, in the presence of a solvent and an ammonolysis agent, carrying out ammonolysis ring-opening reaction on the intermediate II to obtain an intermediate III; and S4, in the presence of a solvent and phosphorus oxychloride, carrying out chlorination and dehydration reaction on the intermediate III to obtain (S)-1-(2-chloracetyl) pyrrolidine-2-formonitrile. The method has the advantages of high chiral purity, simple steps, easily available and cheap raw materials, convenient post-treatment and high yield, and is suitable for industrial production.

PYRROLIDINE AND PIPERIDINE COMPOUNDS

The present technology provides pyrrolidine and piperidine compounds or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and uses thereof. In particular, said compounds may be usefully applied in the treatment and prevention of FAP-mediated diseases.

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.

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%.

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.

Bis-morpholinophosphorylchloride, a novel reagent for the conversion of primary amides into nitriles

Bis-morpholinophosphorylchloride (Bmpc), in the presence of a base, is an efficient dehydrating agent for both aromatic and aliphatic primary amides, and gives corresponding nitriles under mild conditions in god yields and purity. During the reaction the enantiomeric integrity remains intact.

Design, synthesis and exploration of in silico α-amylase and α-glucosidase binding studies of pyrrolidine-appended quinoline-constrained compounds

A series of new pyrrolidine-appended phenoxy-substituted quinoline derivatives were synthesized using 2-chloro-3-formyl quinoline. Initially, the second position of 2-chloro-3-formyl quinoline was successfully converted into various substituted phenoxy-substituted quinolines using various substituted phenols; then, its aldehyde function was reduced to its corresponding alcohols which is in turn converted into its corresponding pyrrolidine-appended phenoxy-substituted quinolines by treating it with 1-(2-chloroacetyl)pyrrolidine-2-carbonitrile. All these newly synthesized compounds were subjected to the in silico studies with the α-amylase and α-glucosidase enzymes to predict the binding affinity.

Synthesis method of vildagliptin intermediate

The invention discloses a synthesis method of a vildagliptin intermediate, and belongs to the technical field of organic synthesis. The method comprises the steps: reacting L-prolinamide serving as aninitial raw material with di-tert-butyl dicarbonate in the presence of a quaternary ammonium salt catalyst and potassium carbonate to obtain N-Boc-L-prolinamide, dehydrating and cyaniding the N-Boc-L-prolinamide and cyanuric chloride in a pure DMF system, adding acid carbonate and anhydrous sulfate, removing a solvent thoroughly, washing, adding p-toluenesulfonic acid, deprotecting, salifying, crystallizing, and obtaining (S)-pyrrolidine-2-carbonitrile p-toluenesulfonate; and finally, carrying out chloroacetylation reaction on the (S)-pyrrolidine-2-carbonitrile p-toluenesulfonate, and crystallizing by using a weak polar solvent to obtain (s)-1-(2-chloracetyl)pyrrolidine-2-carbonitrile. According to the method disclosed by the invention, the generation of impurities is reduced, the productyield loss caused by impurity treatment in the subsequent crystallization process is avoided, and the yield is as high as 80.6%; the purity reaches up to 99.7%; and the whole process is mild in reaction condition, stable in process material and suitable for industrial amplification.