1246610-74-1

Basic information

• Product Name: 2-[[6-[(3R)-3-tert-butoxycarbonylamino-1-piperidinyl]-3,4-dihydro-2,4-dioxo-3-methyl-1(2H)-pyrimidinyl]methyl]benzonitrile
• Synonyms: 2-[[6-[(3R)-3-tert-butoxycarbonylamino-1-piperidinyl]-3,4-dihydro-2,4-dioxo-3-methyl-1(2H)-pyrimidinyl]methyl]benzonitrile;Alogliptin Related Compound 29
• CAS NO: 1246610-74-1
• Molecular Weight: 439.514
• Mol File: 1246610-74-1.mol

Chemical Properties

• CAS DataBase Reference: 2-[[6-[(3R)-3-tert-butoxycarbonylamino-1-piperidinyl]-3,4-dihydro-2,4-dioxo-3-methyl-1(2H)-pyrimidinyl]methyl]benzonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[[6-[(3R)-3-tert-butoxycarbonylamino-1-piperidinyl]-3,4-dihydro-2,4-dioxo-3-methyl-1(2H)-pyrimidinyl]methyl]benzonitrile(1246610-74-1)
• EPA Substance Registry System: 2-[[6-[(3R)-3-tert-butoxycarbonylamino-1-piperidinyl]-3,4-dihydro-2,4-dioxo-3-methyl-1(2H)-pyrimidinyl]methyl]benzonitrile(1246610-74-1)

Safety Data

• Hazardous Substances Data: 1246610-74-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
TBOA is utilized as a research tool in the development of new pharmaceuticals targeting neurological and psychiatric disorders. Its role as a selective antagonist for excitatory amino acid transporters makes it instrumental in studying the effects of glutamate reuptake inhibition on these conditions.
Used in Cancer Treatment Research:
In the field of oncology, TBOA is explored for its potential in cancer treatment. 2-[[6-[(3R)-3-tert-butoxycarbonylamino-1-piperidinyl]-3,4-dihydro-2,4-dioxo-3-methyl-1(2H)-pyrimidinyl]methyl]benzonitrile's ability to modulate neurotransmitter levels may have implications for cancer cell behavior, and ongoing research is investigating these possibilities.
Used in Neuroscience:
TBOA serves as a valuable asset in neuroscience, aiding in the understanding of neurotransmitter dynamics and their impact on brain function. Its neuroprotective effects in animal models highlight its potential in the study and treatment of neurodegenerative diseases.
Used in Drug Development:
As a promising candidate for drug development, TBOA is employed in the creation of new therapeutic agents. Its unique properties as a selective antagonist offer opportunities for designing medications that could address a range of conditions through the modulation of neurotransmitter activity.

Upstream product

• 309956-78-3 (R)-piperidin-3-ylcarbamic acid tert-butyl ester 
• 865758-96-9 2-((6-chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile 
• 1246610-77-4 6-amino-1-(2-cyanobenzyl)-3-methylpyrimidine-2,4(1H,3H)-dione 
• 1217656-59-1 (R)-piperidin-3-ylcarbamic acid tert-butyl ester hydrochloride 
• 4318-56-3 3-methyl-6-chlorouracil 
• 22115-41-9 2-(bromomethyl)benzonitrile 
• 102-09-0 bis(phenyl) carbonate 
• 1246610-71-8 1-(2-cyanobenzyl)-3-methylurea 
• 612-13-5 2-cyanobenzyl chloride 

Downstream Products

• 1246610-76-3 Alogliptin trifluoroacetate 
• 1638544-64-5 Alogliptin benzoate 
• 1246610-75-2 Alogliptin hydrochloride 
• 850649-61-5 alogliptin 

Relevant articles and documents

Preparation method of alogliptin benzoate

The invention discloses a preparation method of alogliptin benzoate. Main starting materials of the preparation method are 6-chloro-3-methyluracil, o-cyanobenzyl bromide, (R)-3-Boc-aminopiperidine andbenzoic acid. According to the method, all indexes meet the specification, meanwhile, dangerous reagents such as sodium hydride and highly toxic methyl iodide are prevented from being used in the reaction process, the requirement for the operation process is not strict, and water-free and oxygen-free conditions are not needed; a high-boiling-point mixed solvent is not used in the reaction, and the solvent is easy to recycle; the selected starting materials are available in the market and easy to obtain, and large-scale production is facilitated; in addition, starting materials or intermediates in the synthetic route are good in stability and convenient to store and control, and genotoxic impurities are avoided in the reaction process; and the synthesis process is environment-friendly.

Simple preparation method of alogliptin benzoate

The invention relates to an alogliptin benzoate preparation method, which comprises that 3,3-dihalogenated-N-methyl acrylamide sequentially reacts with (R)-3-Boc-aminopiperidine and 2-cyano benzylamine to prepare (R)-3-(3-Bocamino)piperidine-1-yl-3-(2-cyano)benzylamino-N-methacrylamide, the obtained material reacts with a carbonylation reagent to prepare alogliptin, and the alogliptin and benzoicacid are subjected to salt forming to prepare alogliptin benzoate. According to the present invention, the method has advantages of inexpensive and easily available raw materials, simple operation andless wastewater, and is suitable for the industrial production of alogliptin benzoate.

A synthetic [...] intermediates

The present invention provides a method for synthesizing an intermediate V. The method comprises: (a) allowing a compound I and a compound II to react while being heated in a solvent under an alkaline condition to obtain an intermediate III; and (b) the intermediate III reacting with a compound IV in the solvent under the alkaline condition to obtain the intermediate V. The intermediate V can be used to synthesize alogliptin.

Alogliptin benzoate preparation method

The present invention provides an alogliptin benzoate preparation method, which comprises treating an intermediate IV reaction solution, and specifically comprises: heating the intermediate IV reaction solution to a temperature of 50-80 DEG C, adding a diluted alcohol while hot, cooling to a temperature of 0-40 DEG C to make the crystal be crystallized, adding water after a lot of the crystals are crystallized, carrying out stirring washing, filtering, and drying to obtain the intermediate IV. According to the present invention, the intermediate IV is prepared by using the one-pot method, a certain amount of the diluted alcohol is added at the high temperature, the saturated solution is formed after the cooling, and the cooling is continuously performed to crystallize, such that the crystal caking problem caused by the direct water precipitation is avoided, the intermediate IV crystal is uniformly dispersed, sticking on the wall and the agglomeration do not exist, the sticking onto the stirring slurry does not exist, the operation is convenient, and the method is suitable for industrial production.

Preparation and after-treatment method for high-purity alogliptin benzoate

The invention relates to optimization and improvement of a preparation and after-treatment method for alogliptin benzoate. In the Boc deprotection process, alkali extraction and acid precipitation methods are adopted, and impurities which do not contain basic groups are effectively removed on the basis of simplifying the process. Moreover, the solvent and temperature control is optimized in the salifying process, and the product quality and yield are improved.

A preparing process of alogliptin benzoate

The invention relates to a preparing process of alogliptin benzoate that is a medicine for treating diabetes mellitus type 2. The process includes reacting 6-chloro-3-methyluracil which is adopted as a raw material and 2-cyanobenzyl bromide to obtain 2-[(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)methyl]benzonitrile, performing a substitution reaction with (R)-3-Boc-aminopiperdine, removing Boc after the reaction is finished to obtain alogliptin, and salting with benzoic acid to obtain the alogliptin benzoate. The process is characterized in that: in the substitution reaction, an acid-binding agent which is potassium carbonate is added, and water is added after the reaction is finished to allow the protected alogliptin to precipitate so as to obtain the alogliptin with Boc protection; and in the deprotection and salting reaction, the alogliptin with Boc protection is deprotected in an ethanol solution of thionyl chloride, and the benzoic acid is added into an ethyl acetate solution of the alogliptin, refluxed and salted to obtain the alogliptin benzoate.

Preparation method of alogliptin

The invention discloses a preparation method of alogliptin. The preparation method comprises following steps: 1), 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidinyl-1-yl methyl)-benzonitrile (IV) and (R)-3-Boc-aminopiperidine are subjected to substitution reaction in the presence of an alkali in an alcoholic solvent so as to obtain a compound IX; and 2) the protecting groups of t-butyloxycarboryl of the compound IX are removed with an acid so as to obtain alogliptin (V). The synthetic route is disclosed in the invention, the alkali used in the step 1) is an organic alkali, the alcoholic solvent is selected from steric hindrance alcohols, and the acid used in the step 2) is selected from carboxylic acids. Advantages of the preparation method are that: the steric hindrance alcohol is taken as the solvent in the synthesis process from the compound IV to the compound V, so that reaction of allyl site alpha-C1 with the solvent and generation of impurities are avoided effectively; the organic carboxylic acid with low acidity is used for removing Boc protecting groups, so that chemical structure destroy is not caused; and using of para-toluenesulfonic acid is avoided, so that introduction of impurities with genotoxicity caused by application of para-toluenesulfonic acid when a lower alcohol is taken as the solvent is avoided.

argues a row sandbank a method for synthesis of benzoic acid

The invention discloses a synthetic method of alogliptin benzoate. The synthetic method of the alogliptin benzoate comprises the steps of carrying out amidation reaction on (R)-3-Boc-amino piperidine and ethyl hydrogen malonate which are taken as raw materials to synthesize (R)-3-(3-Boc-amino piperidine-1-yl)-3-oxo ethyl propionate; then carrying out a ring closing reaction on the (R)-3-(3-Boc-amino piperidine-1-yl)-3-oxo ethyl propionate and 1-(2-cyano-benzyl)-3-methylurea; then carrying out deprotection under an acid condition, so that alogliptin is obtained; and finally carrying out salifying on the alogliptin and benzoic acid, so that the alogliptin benzoate is obtained. The synthetic method of the alogliptin benzoate has the advantages that a synthetic route and technology are simplified and optimized, a reagent is easily available, cost is reduced, total yield is relatively high, using requirement can be met by producing the alogliptin benzoate in a large scale, and the synthetic method of the alogliptin benzoate is efficient, environment-friendly and applicable to industrial production.

A NOVEL PROCESS FOR PREPARATION OF ALOGLIPTIN BENZOATE

The present invention provides a novel process for preparing Alogliptin free base and its benzoate salt which comprises insitu condensation process to produce protected Alogliptin by reacting 6-chloro-3-methylpyrimidine-2, 4(1H, 3H)-dione with 2-(halo methyl) benzonitirle in presence of a base, aprotic solvent followed by insitu reaction with protected (3R)-piperidin-3-amine at elevated temperature. The protected Alogliptinis deprotected to obtain Alogliptin free base and further converted to Alogliptin benzoate.

PROCESS FOR THE PREPARATION OF ALOGLIPTIN

The present invention is based on the discovery of a process for preparing pyrimidin- dione compounds, especially alogliptin and its derivatives, which comprises the reaction of a urea derivative of formula (VIII) with a malonic acid or its derivatives to form intermediates of formulae (VII) or (VII-A), which are subsequently converted to a compound of formula (II) upon introduction of a leaving group X. Compound (II) then reacts with an amine to form compound (I), which is optionally converted to its salts of formula (IV).