1564265-93-5

Basic information

• Product Name: 2-Azabicyclo[3.1.0]hexane-3-carbonitrile, 2-[(2R)-2-aMino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-, (1S,3S,5S)-
• Synonyms: (S,S,S,R)-Saxagliptin;(2'R,2S,cis)-Saxagliptin;Saxagliptin (S,S,S,R)-Isomer;Saxagliptin Impurity 1(S,S,S,R-Isomer);(1S,3S,5S)-2-[(2R)-2-amino-2-(3-hydroxy-1-adamantyl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile;(1S,3S,5S)-2-((R)-2-amino-2-((1r,3S,5R,7S)-3-hydroxyadamantan-1-yl)acetyl)-2-azabicyclo[3.1.0]hexane-3-carbonitrile;2-Azabicyclo[3.1.0]hexane-3-carbonitrile, 2-[(2R)-2-aMino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-, (1S,3S,5S)-
• CAS NO: 1564265-93-5
• Molecular Formula: C18H25N3O2
• Molecular Weight: 315.41
• Mol File: 1564265-93-5.mol

Chemical Properties

• Boiling Point: 548.7±35.0 °C(Predicted)
• Appearance: /
• Density: 1.35±0.1 g/cm3(Predicted)
• PKA: 15.12±0.40(Predicted)
• CAS DataBase Reference: 2-Azabicyclo[3.1.0]hexane-3-carbonitrile, 2-[(2R)-2-aMino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-, (1S,3S,5S)-(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Azabicyclo[3.1.0]hexane-3-carbonitrile, 2-[(2R)-2-aMino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-, (1S,3S,5S)-(1564265-93-5)
• EPA Substance Registry System: 2-Azabicyclo[3.1.0]hexane-3-carbonitrile, 2-[(2R)-2-aMino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-, (1S,3S,5S)-(1564265-93-5)

Safety Data

• Hazardous Substances Data: 1564265-93-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Saxagliptin is used as an active pharmaceutical ingredient for the treatment of type 2 diabetes. It works by inhibiting the DPP-IV enzyme, which in turn slows down the degradation of insulin and glucagon-like peptide-1 (GLP-1). This leads to an increased insulin production and a decreased glucagon release, resulting in better blood glucose control.
Additionally, saxagliptin may be used as an impurity in the development and manufacturing process of Saxagliptin (S143500), a medication specifically designed to manage type 2 diabetes. The presence of (2'R,2S,cis)-Saxagliptin as an impurity is important to monitor and control, as it can impact the safety, efficacy, and quality of the final drug product.

Upstream product

• 945667-22-1 saxagliptin monohydrate 
• 361442-00-4 (αS)-α-[[(1,1-dimethylethoxy)carbonyl]-amino]-3-hydroxytricyclo[3.3.1.1^3,7]decane-1-acetic acid 
• 709031-39-0 (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide hydrochloride 
• 709031-43-6 3-cyano-(αS)-α-(3-hydroxytricyclo[3.3.1.1^3,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid 1,1-dimethylethyl ester 
• 865999-64-0 (2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetic acid hydrochloride 
• 1564267-10-2 (S)-N-Boc-3-hydroxyadamantylglycine-D-trans-4,5-methanoprolinenitrile 
• 102502-64-7 (S)-(+)-(adamant-1-yl)aminoacetic acid hydrochloride 
• 932040-48-7 1-tert-butyl 2-ethyl (2R)-5-hydroxypyrrolidine-1,2-dicarboxylate 
• 1091626-35-5 1-tert-butyl 2-ethyl (2R)-2,3-dihydro-1H-pyrrole-1,2-dicarboxylate 
• 871727-40-1 2-tert-butyl 3-ethyl (1S,3R,5S)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate 
• 361441-97-6 (alpha S)-alpha-[[(1,1-dimethylethoxy)carbonyl]amino]tricyclo[3.3.1.1^3,7]decane-1-acetic acid 
• 144978-12-1 1-tert-butyl 2-ethyl (2R)-5-oxopyrrolidine-1,2-dicarboxylate 
• 68766-96-1 ethyl (R)-2-pyrrolidone-5-carboxylate 
• 178172-26-4 (5S)-4,5-dihydro-1H-pyrrol-1,5-dicarboxylic acid [1-(1,1-dimethylethyl)] 5-ethyl ester 

Downstream Products

• 841302-24-7 5-hydroxy-saxagliptin 

Relevant articles and documents

Preparation of saxagliptin, a novel DPP-IV inhibitor

The commercial-scale synthesis of the DPP-IV inhibitor, saxagliptin (1), is described from the two unnatural amino acid derivatives 2 and 3. After the deprotection of 3, the core of 1 is formed by the amide coupling of amino acid 2 and methanoprolinamide

Preparation method of saxagliptin monohydrate crystal form

The invention provides a preparation method of a saxagliptin monohydrate crystal form, wherein the preparation method comprises the steps: firstly, mixing Boc protected saxagliptin, water, an alcohol solvent and strong inorganic acid for reaction to obtain a mixture of saxagliptin salts; adding an organic solvent into the mixture for extraction, adjusting the pH value of the mixture with alkali, and performing liquid separation to obtain an organic phase rich in saxagliptin; and finally, concentrating the organic phase rich in saxagliptin until a solid is separated out, adding absolute ethyl alcohol and isopropanol, then adding n-heptane or n-hexane, and crystallizing to obtain the saxagliptin monohydrate crystal form. The method is short in time consumption, low in requirements on reaction conditions, reaction equipment and operation and suitable for industrial production, and the prepared saxagliptin monohydrate crystal form is high in yield and purity.

Method for preparing saxagliptin

The invention discloses a method for preparing saxagliptin, and belongs to the technical field of drug synthesis. The method comprises the following steps: (a) converting amide on a compound shown ina formula I into cyano and removing Boc groups to obtain a compound shown in a formula II; (b) condensing the compound shown in the formula II and a compound shown in a formula III to obtain a compound shown in a formula IV; and (c) removing Boc groups on the compound shown in the formula IV to obtain a compound shown in a formula V. According to the method, different raw materials and reaction reagents are selected, and a process route is changed, so that four procedures of salifying, condensing, cyanating and de-protecting are shortened into three procedures of cyanating, condensing and de-protecting; meanwhile, cyanating and condensation reaction are realized at the room temperature, the requirements on reaction conditions are reduced, and industrial production can be realized.

Preparation method of saxagliptin

The invention discloses a preparation method of saxagliptin. The preparation method comprises the following steps: reacting (S)-N-tert-butyloxycarbonyl-(3-hydroxyadamantan-1-yl)glycine with (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carbonitrile hydrochloride under the catalysis of 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate/N,N-diisopropylethylamine to obtain (1S)-2-(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3,1,0]hex-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxoethyl tert-butyl carbamate, and removing protecting groups under acidic adjustment so as to obtain (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxytricyclo[3.3.1.13,7]decan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-nitrile. The method has the advantages of safety, easiness in operation, usage cheap and easily available raw materials, mild and easily controllable reaction conditions, simple post-reaction treatment, high yield and the like.

Preparation method of medication saxagliptin for treating diabetes

The invention provides a preparation method of saxagliptin with a shorter synthetic route. (S)-3-amino-3-cyano-propionic ether protected by diethyl acetylenedicarboxylate and an amino group is used asa starting material in the presence of an organic phosphine ligand and a palladium catalyst, and is subjected to cyclization, decarboxylation and cyclopropanation to obtain an intermediate product (1S, 3S, 5S)-2-azabicyclo[3.1.0]hexane-3-carbonitrile p-toluenesulfonate, and then the intermediate product is reacted with carboxyl-activated (S)-N-t-butyloxycarboryl-(3-hydroxyadamantane-1-yl)glycineto increase the reaction rate and obtain a saxagliptin product with a high yield and high purity, the reaction route is greatly shortened, the yield in each step is high, the reaction time is short, the production cost is reduced, and industrial production is facilitated.

Novel intermediates for preparing saxagliptin, preparing methods thereof and preparing methods of saxagliptin using the same

The present invention relates to a novel intermediate used in the production of saxagliptin, a production method thereof, and a method for producing saxagliptin using the same. According to the present invention, the use of the novel intermediate which is represented by chemical formula 1 enables the production of high purity saxagliptin or a pharmaceutically acceptable salt thereof in high yield through a simple and economical way.COPYRIGHT KIPO 2017

Method for synthesizing Saxagliptin and intermediate

A method for synthesizing Saxagliptin and its intermediate is disclosed. According to the method, propylphosphonic anhydride is used in a peptide coupling reaction and a dehydration reaction of formamide, thus reducing side reaction of racemization and decreasing toxicity of aftertreatment; and ethylene glycol diethyl ether is preferably used as a solvent in the dehydration reaction of formamide, thus increasing reaction temperature of propylphosphonic anhydride dehydration and shortening reaction time so as to reduce side reaction of racemization.

PROCESS FOR PREPARING DIPEPTIDYL PEPTIDASE IV INHIBITORS AND INTERMEDIATES THEREFOR

A process for preparing an amine of the structure which comprises a. treating an aqueous solution of a keto acid of the structure with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase and/or formate dehydrogenase enzyme (PDH/FDH); and b. adjusting pH of the reaction mixture with sodium hydroxide to form the desired amine which is substantially free of undesirable excess ammonium ions.

PROCESS FOR PREPARATION OF (IS, 3S, 5S)-2-[(2S)-2-AMIN0-2-(3-HYDROXY-l-ADAMANTYL) ACETYL]-2-AZABICYCLO [3.1.0] HEXANE-3-CARBONITRILE

Provided are novel processes for the preparation of Saxagliptin and novel intermediates employed in the process for preparing Saxagliptin.

Synthesis and biological evaluation of all eight stereoisomers of DPP-IV inhibitor saxagliptin

All eight stereoisomers of saxagliptin have been synthesized and evaluated for their inhibitory activity against DPP-IV. It was unambiguously confirmed that the configuration of saxagliptin was critical to potent inhibition of DPP-IV. Docking study was performed to elucidate the configuration-activity relationship of saxagliptin stereoisomers. Tyr662 and Tyr470 have been suggested as the key residues of DPP-IV interacting with the inhibitors. This work provides valuable information for further inhibitor design against DPP-IV.