823817-55-6

Basic information

• Product Name: Sitagliptin Impurity 1
• Synonyms: Sitagliptin Impurity 1
• CAS NO: 823817-55-6
• Molecular Formula: C16H15F6N5O
• Molecular Weight: 407.3136192
• Mol File: 823817-55-6.mol

Chemical Properties

• Boiling Point: 529.9±60.0 °C(Predicted)
• Appearance: /
• Density: 1.61±0.1 g/cm3(Predicted)
• PKA: 7.20±0.10(Predicted)
• CAS DataBase Reference: Sitagliptin Impurity 1(CAS DataBase Reference)
• NIST Chemistry Reference: Sitagliptin Impurity 1(823817-55-6)
• EPA Substance Registry System: Sitagliptin Impurity 1(823817-55-6)

Safety Data

• Hazardous Substances Data: 823817-55-6(Hazardous Substances Data)

Usage

Uses

Sitagliptin Impurity 1 does not have direct applications in the pharmaceutical or other industries due to its classification as an impurity. However, its management and control are essential in the following areas:
Used in Pharmaceutical Manufacturing:
Sitagliptin Impurity 1 is managed as a critical quality attribute for ensuring the purity and safety of sitagliptin formulations. It is used as a parameter for monitoring and controlling the manufacturing process to comply with regulatory standards and to guarantee the effectiveness and safety of the sitagliptin medication for patients.
Used in Quality Control and Assurance:
Sitagliptin Impurity 1 is utilized as a benchmark for quality control and assurance in the pharmaceutical industry. It is used for identifying and quantifying the levels of impurities in sitagliptin drug products to ensure that they meet the required specifications and do not compromise the drug's therapeutic benefits or patient safety.
Used in Regulatory Compliance:
Sitagliptin Impurity 1 is monitored and controlled as part of the regulatory compliance process in the pharmaceutical industry. It is used to ensure that sitagliptin drug products adhere to the established guidelines and standards set by regulatory authorities, thereby maintaining the integrity and reliability of the medication.

Upstream product

• 764667-65-4 1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione 
• 209995-38-0 (2,4,5-trifluorophenyl)acetic acid 
• 847445-81-2 dehydrositagliptin 
• 1283096-74-1 (S)-3-hydroxy-4-(2,4,5-trifluorophenyl)butanenitrile 
• 1380521-84-5 tert-butyl (E)-4-(2',4',5'-trifluorophenyl)but-2-enoate 
• 1380521-85-6 tert-butyl (R,R)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4-(2',4',5'-trifluorophenyl)butanoate 
• 1380521-86-7 tert-butyl (R,R)-3-[N-benzyl-N-(α-methyl-p-methoxybenzyl)amino]-4-(2',4',5'-trifluorophenyl)butanoate 
• 1380521-87-8 C₂₅H₂₄F₃NO₂*ClH 
• 1380521-88-9 (R,R)-N-benzyl-N-(α-methylbenzyl)-1-(2',4',5'-trifluorophenyl)-4-oxo-4-{3''-(trifluoromethyl)-5'',6''-dihydro-1'',2'',4''-triazolo[4,3-α]pyrazin-7''(8''H)-yl}butan-2-amine 
• 1393363-87-5 (R)-N-benzyl-1-(2',4',5'-trifluorophenyl)-4-oxo-4-{3''-(trifluoromethyl)-5'',6''-dihydro-1'',2'',4''-triazolo[4,3-α]pyrazin-7''(8''H)-yl}butan-2-amine 
• 111991-20-9 2-(2,4,5-trifluorophenyl)acetaldehyde 
• 1169707-29-2 (R,Z)-3-[(1-phenylethyl)amino]-1-{3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)but-2-en-1-one 
• 762240-92-6 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride 
• 654671-78-0 sitagliptin phosphate 

Downstream Products

• 1190094-97-3 (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 (-)dibenzolyl-L-tartaric acid salt 
• 1219440-27-3 (2S)-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 (-)dibenzolyl-L-tartaric acid salt 
• 1219440-25-1 dibenzoyl-D-tartaric acid (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 
• 1219440-26-2 dibenzoyl-D-tartaric acid (2S)-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 
• 1219440-29-5 (S)-(+)-O-acetylmandelic acid (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 
• 1219440-30-8 (S)-(+)-O-acetylmandelic acid (2S)-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 

Relevant articles and documents

Two methods for the preparation of sitagliptin phosphate: Via chemical resolution and asymmetric hydrogenation

Two effective processes have been developed for the preparation of sitagliptin phosphate. The approach of chemical resolution obtained R-sitagliptin in five steps from commercially available starting materials using the inexpensive NaBH4 to reduce the enamine and then using (-)-di-p-toluoyl-l-tartaric acid to resolve racemates in 11% yield overall. The route successfully avoids the use of expensive noble metal as catalysts compared with traditional synthesis methods, resulting in greatly reduced costs and simplified synthetic routes. Other alternative asymmetric hydrogenation of β-ketomide routes for the synthesis of sitagliptin were found, two of the intermediates were synthesized for the first time. This journal is

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.

Process method for improving yield and purity of sitagliptin

The invention provides a process method for improving yield and purity of sitagliptin, which comprises the following steps: mixing Boc sitagliptin as shown in a formula iii with solvent ester and acid, carrying out hydrolysis reaction at 0-50 DEG C, neutralizing with acid and alkali after the reaction is finished, and removing a water layer to obtain an organic layer containing sitagliptin as shown in a formula iv. The process method disclosed by the invention has the advantages that degradation of sitagliptin iv in reaction and post-treatment processes can be avoided, so that the yield and quality of sitagliptin iv are effectively improved.

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.

IMPROVED PROCESS FOR PREPARATION OF SITAGLIPTIN

Provided herein is a process for the preparation of specific enantiomeric Sitagliptin with good chiral purity and higher yield using improved biocatalyst and by engineering an enzyme to mediate the efficient conversion of ketoamide to obtain enantiomerically pure Sitagliptin in presence of an amino group donor.

HIGHLY EFFICIENT PROCESS FOR THE PREPARATION OF SITAGLIPTIN VIA RHODIUM CATALYZED ASYMMETRIC HYDROGENATION

The present invention provides highly efficient process for the preparation of enantiomerically enriched Sitagliptin of Formula (Ia). More particularly, a direct rhodium catalyzed asymmetric hydrogenation in the presence of bis-phosphine chiral ligand has been developed to yield enantiopure Sitagliptin product with the highest enantiomeric excess of 85-99.9%.

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 sitagliptin free alkali monomer (by machine translation)

The invention belongs to the technical field of chemical pharmacy, and particularly relates to a preparation method, of sitagliptin salt or other water-soluble salt. after the reaction, is dissolved in water, with sodium hydroxide solution or other inorganic alkalis pH, at a temperature of 20 - 45 °C DEG C for, drying to obtain, g of sitagliptin free base monomer, with high yield after dissolution . The method is high. low, cost and easy, to obtain a high yield of, sitagliptin free base monomer (. s,). (by machine translation)

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.