486460-23-5

Usage

Uses

Used in Pharmaceutical Industry:
Sitagliptin N-Boc IMpurity is used as an intermediate compound for the synthesis of Sitagliptin, a DPP-4 inhibitor, which is essential for glycemic control in patients with type 2 diabetes. Sitagliptin N-Boc IMpurity helps in the development of Sitagliptin by providing a protective N-Boc group that prevents unwanted side reactions during the synthesis process.
Used in Research and Development:
Sitagliptin N-Boc IMpurity is also used in research and development for the study of DPP-4 inhibitors and their potential applications in the treatment of type 2 diabetes. Researchers can use Sitagliptin N-Boc IMpurity to investigate the structure-activity relationship of Sitagliptin and other related compounds, leading to the discovery of more effective and safer treatments for diabetes.
Used in Quality Control:
In the pharmaceutical manufacturing process, Sitagliptin N-Boc IMpurity is used for quality control purposes. It helps ensure that the final product, Sitagliptin, meets the required purity and potency standards. By monitoring the presence and concentration of this impurity, manufacturers can maintain the quality and consistency of Sitagliptin in the final drug product.

Upstream product

• 486460-00-8 (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 
• 762240-92-6 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride 
• 881995-73-9 3-(R)-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)butyric acid methyl ester 
• 1361050-65-8 (E)-1-benzyl-4-methyl-2-(2,4,5-trifluorobenzylidene)succinate 
• 1361050-69-2 4-methoxy-4-oxo-2-(2,4,5-trifluorobenzyl)butanoic acid 
• 1361050-70-5 (R)-4-methoxy-4-oxo-2-(2,4,5-trifluorobenzyl)butanoic acid 
• 1380298-43-0 C₁₇H₂₇NO₆S 
• 327-52-6 1-bromo-2,4,5-trifluorobenzene 
• 191655-46-6 tert-butyl (S)-(4-((tert-butyldimethylsilyl)oxy)-1-hydroxybutan-2-yl)carbamate 
• 59408-74-1 (S)-2-((tert-butoxy)carbonylamino)-4-(phenylmethoxy)butyric acid 
• 247093-36-3 (S)-2-(tert-butoxycarbonylamino)-4-(methylthio)butyl methanesulfonate 
• 1380243-18-4 C₁₀H₁₉NO₂S 
• 1380243-23-1 (S)-tert-butyl 2-(2-(tert-butyldimethylsilyloxy)ethyl)aziridine-1-carboxylate 
• 1380243-24-2 C₁₁H₂₁NO₄ 

Downstream Products

• 654671-78-0 sitagliptin phosphate 
• 654671-78-0 (2R)-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-amine phosphate 
• 881995-69-3 (R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid methyl ester 
• 486459-71-6 (2R)-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-amine hydrochloride 
• 486459-71-6 Sitagliptin hydrochloride 
• 486460-32-6 sitagliptin 

Relevant academic research and scientific papers

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.

Synthesis method of sitagliptin free alkali

The invention belongs to the field of organic chemistry, and particularly discloses a synthesis method of sitagliptin free alkali. The synthesis method comprises the following specific steps: (1) dissolving (3R)-N-tert-butyloxycarbonyl-3-amino-4-(2,4,5-trifluorophenyl) butyric acid and organic alkali in an organic solvent, adding a phosphorus-containing condensing agent, then adding 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazol[4,3-alpha]pyrazine hydrochloride to prepare a compound represented by a formula (II); and (2) removing t-butyloxycarboryl from the compound shown in the formula II under the action of acid to obtain a compound I namely sitagliptin free alkali. The method is mild in process reaction condition, easy to control, short in reaction time, free of extraction, simple to operate and beneficial to industrial production, and the process cost is reduced; and the prepared compound shown in the formula I is high in yield, high in purity and free of heavy metal residues.

Synthesis method of sitagliptin free alkali and sitagliptin phosphate monohydrate

The invention relates to a synthesis method of sitagliptin free alkali and sitagliptin phosphate monohydrate. According to the method, dry HOBt is removed or changed into HOBt hydrate, a solvent DMF is removed in the process, and a simple solvent easy to recover is used in the production process, so that the production cost is reduced, and the reaction safety is improved. According to the invention, with the in-situ process from a compound represented by a formula 2 to a compound represented by a formula 6, the yield can be improved, the operation steps can be reduced, and the methanol or isopropanol IPA is replaced with other solvents so as to avoid the generation of impurities represented by a formula 7, a formula 8 and a formula 9, such that the product purity and the yield can be substantially improved, and the HPLC purity of the sitagliptin free alkali is more than 99%.

Preparation method of chiral 4 - aryl - β β-amino acid derivative

Provided is a method for preparing a chiral 4-aryl-β-amino acid derivative. The preparation method comprises hydrogenating an enamine compound having a structure as shown in Formula III in an organic solvent in the presence of a catalyst containing a transition metal and BIBOPs. The preparation method of the present invention uses a small amount of a selected asymmetric catalyst, and has a simple operation, mild reaction conditions, a high yield, a high stereoselectivity, and better industrial application and economic values.

AN IMPROVED PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND ITS INTERMEDIATES

The present invention relates to a process for the preparation of novel intermediates useful for the preparation of Sitagliptin or its pharmaceutically acceptable salts. The present invention relates to an efficient process for the preparation of Sitagliptin intermediates. The present invention relates to an improved process for the preparation of Sitagliptin or its pharmaceutically acceptable salts.

Preparation method of tert-butyloxycarbonyl-sitagliptin

The invention discloses a preparation method of tert-butyloxycarboryl-sitagliptin. The preparation method comprises the following steps: taking BOC-(R)-3-amino-4-(2, 4, 5-trifluorophenyl) butyric acidas a main raw material; under condition of adjustment by alkalinity, adding acyl chloride, carrying out a reaction at -20 to 50 DEG C for 1 to 10 h, adding 3-trifluoromethyl-5, 6, 7, 8-tetrahydro-1,2, 4-triazolo[4, 3-a] pyrazine hydrochloride at the temperature of -20 to 50 DEG C for 1 to 10 h, adding water at the temperature, carrying out stirring crystallization, carrying out filtering and carrying out drying. The method has the advantages of reasonable reaction steps, mild reaction conditions, fewer side reactions, simple and convenient post-treatment, safety and environmental protection;the yield of synthesized tert-butyloxycarboryl-sitagliptin is high and can reach 92% or above, and the purity of a finished product is also high and can reach 99.5% or above.

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.

Preparation Method Camphorsulfonic acid Salt of Sitagliptin

The present invention provides a method for manufacturing a camsylate salt of sitagliptin and the camsylate salt manufactured by a manufacturing method thereof. The manufacturing method of the present invention has a simple manufacturing process, thereby being able to synthesize a sitagliptin camsylate salt economically in terms of time and/or cost. Therefore, it is possible to be usefully applied for mass production.COPYRIGHT KIPO 2019

BOC-(R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid condensation impurity and preparation method thereof

The invention provides a sitagliptin phosphate important intermediate BOC-(R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid condensation impurity and a preparation method and preparation thereof. TheBOC-(R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid condensation impurity and the preparation method thereof have important significance for the following industrial production of bulk drugs.

Mechanistic Insight into Asymmetric Hetero-Michael Addition of α,β-Unsaturated Carboxylic Acids Catalyzed by Multifunctional Thioureas

Carboxylic acids and their corresponding carboxylate anions are generally utilized as Br?nsted acids/bases and oxygen nucleophiles in organic synthesis. However, a few asymmetric reactions have used carboxylic acids as electrophiles. Although chiral thioureas bearing both arylboronic acid and tertiary amine were found to promote the aza-Michael addition of BnONH2 to α,β-unsaturated carboxylic acids with moderate to good enantioselectivities, the reaction mechanism remains to be clarified. Detailed investigation of the reaction using spectroscopic analysis and kinetic studies identified tetrahedral borate complexes, comprising two carboxylate anions, as reaction intermediates. We realized a dramatic improvement in product enantioselectivity with the addition of 1 equiv of benzoic acid. In this aza-Michael reaction, the boronic acid not only activates the carboxylate ligand as a Lewis acid, together with the thiourea NH-protons, but also functions as a Br?nsted base through a benzoyloxy anion to activate the nucleophile. Moreover, molecular sieves were found to play an important role in generating the ternary borate complexes, which were crucial for obtaining high enantioselectivity as demonstrated by DFT calculations. We also designed a new thiourea catalyst for the intramolecular oxa-Michael addition to suppress another catalytic pathway via a binary borate complex using steric hindrance between the catalyst and substrate. Finally, to demonstrate the synthetic versatility of both hetero-Michael additions, we used them to accomplish the asymmetric synthesis of key intermediates in pharmaceutically important molecules, including sitagliptin and α-tocopherol.