23500-10-9

Usage

Uses

Used in Pharmaceutical Industry:
CHLOROAC-PRO-OH is used as a key intermediate in the synthesis of vildagliptin impurity. It plays a crucial role in the preparation of this impurity, which is essential for the development and quality control of vildagliptin, a medication used to treat type 2 diabetes. The presence of CHLOROAC-PRO-OH in the synthesis process helps ensure the purity and efficacy of the final pharmaceutical product.

InChI:InChI=1/C7H10ClNO3/c8-4-6(10)9-3-1-2-5(9)7(11)12/h5H,1-4H2,(H,11,12)/t5-/m0/s1

Upstream product

• 2812-47-7 pyrrolidine-2-carboxylic acid amide 
• 79-11-8 chloroacetic acid 
• 147-85-3 L-proline 
• 79-04-9 chloroacetyl chloride 

Downstream Products

• 565453-40-9 vildagliptin carboxylic acid 
• 1036959-23-5 (2S)-1-{[{2[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}[(3-hydroxytricyclo[3.3.1.1(3,7)]dec-1-yl)amino]]acetyl}pyrrolidine-2-carbonitrile 
• 274901-16-5 vildagliptin 
• 274901-37-0 1-chloroacetyl-2-(S)-cyanopyrrolidine 
• 914070-99-8 (S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 

Relevant academic research and scientific papers

Vildagliptin diketopiperazine and preparation method thereof

The preparation method comprises the following steps: (1) L - proline is dissolved, and chloroacetyl chloride is mixed, and the compound 1 is generated. (2) Compound 1 and 3 - amino -1 - adamantanol undergo a substitution reaction under basic conditions to give compound 2. (3) The compound 2 is cyclised under basic conditions, i.e. diketopiperazine. The preparation method of the vildagliptin diketopiperazine provided by the invention takes L - proline as a raw material, is synthesized through chloroacetylation, substitution and dehydration 3 steps, is simple in synthesis method, mild and easy to control in reaction conditions, cheap in raw material, and capable of 98.0% effectively reducing the synthesis cost.

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%.

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.

Preparation process of vildagliptin impurity

The invention discloses a preparation process of a vildagliptin impurity, namely 2-(3-hydroxy adamantane-1-yl) hexahydropyrrole [1, 2-a] piperazine-1, 4-diketone. According to the process, L-proline is used as an initial raw material, and 2-(3-hydroxy adamantane- 1-yl) hexahydropyrrole [1, 2-a] piperazine-1, 4-diketone is prepared through secondary N-chloracetylation reaction, amino substitution and intramolecular cyclization. The method is mainly characterized in that reaction steps and time are shortened, and expensive catalysts and tedious operation means are not involved in the whole reaction process. The preparation process has the advantages of easily available raw materials, mild and easily controllable reaction conditions and high product purity, and the vildagliptin impurity can be used as a reference substance for vildagliptin bulk drug quality control.

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)

Direct Synthesis of Cyanopyrrolidinyl β-Amino Alcohols for the Development of Diabetes Therapeutics

Cyanopyrrolidinyl β-amino alcohols are novel scaffolds with potential for a wide array of pharmacological properties. We have discovered that we can selectively access these scaffolds from simple and inexpensive commercially available chemicals in few synthetic steps with minimal purification. We have produced a 36-compound library of these scaffolds and tested them as dipeptidyl peptidase IV (DPP4) inhibitors. These novel inhibitors are useful in the treatment of diabetes and inflammatory disorders.

A facile and economical method to synthesize vildagliptin

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%.

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.

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.

A cost-effective method to prepare pure vildagliptin

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%.