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
• Article Data: 116

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

General Description

Sitagliptin Impurity 1 is a chemical substance that falls under the class of impurities associated with the drug sitagliptin, which is used to treat type 2 diabetes. This impurity is a potential by-product that may be present in sitagliptin formulations and needs to be closely monitored during the manufacturing process to ensure the purity and safety of the final drug product. It is crucial to identify and quantify the levels of Sitagliptin Impurity 1 to comply with regulatory standards and ensure the effectiveness and safety of the sitagliptin medication for patients. Proper control and management of this impurity are essential to guarantee the quality and efficacy of the sitagliptin drug.

Upstream product

• 1259320-67-6 2-(R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]-7(8H)-pyrazinyl]-1-(2,4,5-trifluorophenyl)-2-butanamine dodecylthio carbamate 
• 847445-81-2 dehydrositagliptin 
• 883267-70-7 2-(2,4,5-trifluorophenyl)ethanol 
• 1151240-88-8 3-oxo-4-(2,4,5-trifluorophenyl)-butyric acid ethyl ester 
• 767340-03-4 (Z)-3-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 
• 823817-56-7 (R/S)-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 
• 209995-38-0 (2,4,5-trifluorophenyl)acetic acid 
• 1219440-31-9 (2S)-N-trifluoroacetyl-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 
• 1253056-14-2 (R/S)-3-(1,3-dioxoisoindolin-2-yl)-1-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)butan-1-one 
• 1253056-15-3 (Z)-3-(hydroxyimino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one 
• 762240-92-6 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride 
• 1351564-27-6 3-nitro-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-3-en-1-one 
• 1433546-53-2 (R/S)-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-yl methanesulfonate 

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 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%.

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.