62613-82-5

Basic information

• Product Name: Oxiracetam
• Synonyms: 4-HYDROXY-2-OXOPYRROLIDINE-N-ACETAMIDE;4-hydroxy-2-oxo-1-pyrrolidineacetamid;4-hydroxy-2-oxo-1-pyrrolidineacetamide;4-hydroxypiracetam;ct-848;hydroxypiracetam;Oxiracetam, >=99%;Oxiracetam 99.7%
• CAS NO: 62613-82-5
• Molecular Formula: C₆H₁₀N₂O₃
• Molecular Weight: 158.16
• EINECS: 2017-001-1
• Product Categories: Pharmaceutical material and intermeidates;APIs;API;(intermediate of oxiracetam);Amines;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Brain health drug;Nootropic;pharmaceutical intermediate
• Mol File: 62613-82-5.mol
• Article Data: 17

Chemical Properties

• Melting Point: 165-168 °C
• Boiling Point: 494.6 °C at 760 mmHg
• Flash Point: 252.9 °C
• Appearance: white crystalline powder
• Density: 1.416
• Vapor Pressure: 7.39E-12mmHg at 25°C
• Refractive Index: 1.57
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly, Heated), Methanol (Slightly, Heated)
• PKA: 13.76±0.20(Predicted)
• Merck: 14,6942
• CAS DataBase Reference: Oxiracetam(CAS DataBase Reference)
• NIST Chemistry Reference: Oxiracetam(62613-82-5)
• EPA Substance Registry System: Oxiracetam(62613-82-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: UX9656638
• Hazardous Substances Data: 62613-82-5(Hazardous Substances Data)

Usage

Indications and Usage

Oxiracetam is a more potent derivative of the nootropic drug piracetam. They were developed in 1974 by the Italian company ICF and went on sale in 1987. Oxiracetam is a Piracetam derivative and excites the central nervous system, promotes brain metabolism, significantly increases and promotes memory retention, and effectively treats senile memory and mental decline. It is used to treat brain dysfunction psychiatric syndrome and mental disorders. It can improve the memory and learning abilities of patients with senile dementia or memory disorders. It is suitable for treating neural dysfunction, memory disorder and intelligence disorders caused by brain damage. It can also be used as a recovery treatment for neurosis, brain trauma, encephalitis, and other brain diseases. Oxiracetam’s greatest advantage is that it is very soluble in water, making it suitable for injection. Research shows that Oxiracetam has higher pharmacological activity and significant curative effects compared to Piracetam.

Mechanisms of Action

Oxiracetam’s mechanisms of action are similar to those of Piracetam. It promotes the binding of phosphorylcholine and phosphoethanolamine, increases the ratio of ATP/ADP in the brain, and increases the binding of protein with nucleic acids in the brain, thus improving the memory and learning ability of patients with senile dementia and memory disorder.

Pharmacokinetics

After intake, most of the drug will not accumulate in the body and will be excreted through urine in its original form. It is well-absorbed and well-tolerated.

Clinical Research

Animal trials showed that in all types of behavioral experiments, Oxiracetam can improve memory retention and learning ability, reduce brain shocks’ damage on memory, and prevent the learning abilities of rats suffering from spontaneous hypertensive cerebrovascular injury from decreasing. It can also increase acetylcholine circulation in rats’ skin and hippocampus, thus increasing affinity for choline uptake.

Originator

ISF (Italy)

Biochem/physiol Actions

Nootropic agent, improves learning and memory, and prevents impairment of cognitive functions. Its mechanism of action in not yet known, but it is suggested to modulate glutamatergic and cholinergic neurotransmission. Protein kinase C may be involved.

Purification Methods

This nootropic (Alzheimer) drug is purified by recrystallisation from MeOH or aqueous Me2CO and dried in vacuo. [NMR, IR: Pifferi & Pinza Farmaco Ed Sci 32 602 1977, Banfi et al. Farmaco Ed Sci 39 16 1984, Gouilaev & Senning Brain Research Rev 19 180 1994.]

InChI:InChI=1/C6H10N2O3/c7-5(10)3-8-2-4(9)1-6(8)11/h4,9H,1-3H2,(H2,7,10)

Upstream product

• 62613-81-4 ethyl (4-hydroxy-2-oxopyrrolidin-1-yl)acetate 
• 10488-68-3 methyl 4-chloro-3-hydroxybutanoate 
• 598-41-4 H-Gly-NH₂ 
• 85614-53-5 methyl 2,4-dioxo-1-pyrrolidinacetate 
• 154522-71-1 2-(4-hydroxypyrrolidin-2-on-1-yl)-ethyl acetate 
• 4509-09-5 Methyl (+/-)-3,4-epoxybutanoate 
• 1668-10-6 glycinamide hydrochloride 
• 110104-61-5 ethyl (2,5-dihydro-4-methoxy-2-oxo-1H-pyrrol-1-yl)acetate 

Downstream Products

• 62833-66-3 2,5-Dihydro-2-oxo-1H-pyrrol-1-acetamid 
• 77191-37-8 4-hydroxy-2-oxo-1-pyrrolidine acetic acid 
• 1392812-96-2 C₆H₁₀N₂O₃*C₇H₆O₄ 
• 1392812-94-0 C₆H₁₀N₂O₃*C₇H₆O₅ 

Relevant articles and documents

Preparation method of 4-hydroxy-2-oxo-1-pyrrolidine acetamide

The invention belongs to the technical field of drug synthesis, in particular to a preparation method of 4-hydroxy-2-oxo-1-pyrrolidine acetamide. The 4-hydroxy-2-oxo-1-pyrrolidine acetamide is produced by intramolecular dehydration of 4-hydroxy-2-oxo-1-pyrrolidine acetic acid to obtain lactone which is then reacted with ammonia water. The preparation method of the 4-hydroxy-2-oxo-1-pyrrolidine acetamide has the advantages of short reaction period, mild conditions, low production cost, high product yield, good quality and the like, so that the method is suitable for industrial large-scale production.

Preparation method 2 - (4 -hydroxy -2 - oxo -1 - pyrrolidinyl) acetamide (by machine translation)

The invention relates to the field, organic synthesis and medicine technology. In particular, the invention provides a method for preparing 2 - (4 -hydroxy -2 - oxo -1 - pyrrolidinyl) acetamide, which uses methyl 4 - chloroacetoacetate as a starting material, condenses, crystallizes and crystallizes after carbonyl reduction to obtain a target product, and the total yield is approximately unitz 90% is left and right. The method optimizes the reaction steps by improving the synthesis route, namely the 2 - (4 - hydroxyl -2 - oxo -1 - pyrrolidinyl) acetamide, and shortens the production cycle, and shortens the production cycle. The production cost, as well as the emission. The method is cheap and easy to obtain, simple and convenient to operate, low in impurities, high in yield, and particularly suitable for industrial production. (by machine translation)

A synthesis process of oxiracetam

The invention discloses a synthetic method for an anti-senile dementia drug of oxiracetam (I), and mainly provides a novel synthetic route. The method comprises the following steps of reacting a compound (when R is -Me and NO2) shown as a formula (V) with glycinamide hydrochloride of a compound shown as a formula (VI) under an alkaline condition to obtain a compound (wherein R is -Me and NO2) shown as a formula (IV); reacting the compound (wherein R is -Me and NO2) shown as the formula (IV) with ethyl 4-chloro-3-hydroxybutyrate of a compound shown as a formula (III) to obtain a compound (wherein R is -Me and NO2) shown as a formula (II); then removing protection groups under an acidic condition and intramolecularly cyclizing to obtain a compound shown as the formula (I) of 4-hydroxy-2-oxo-1-pyrrolidine acetamide, the compound (I) being oxiracetam. According to the synthetic route, raw materials and reagents have low toxicity, low cost and easy availability. The synthetic route is simple to operate, has relatively high yield and is suitable for industrial production.

A oxiracetam intermediate and its preparation method and application

The invention provides an oxiracetam intermediate as well as a preparation method and application thereof. The oxiracetam intermediate is a solid or a crystalline solid, low in preparation cost, and easy to purify and store, and can be used for efficiently preparing oxiracetam. The structural formula is as shown in the specifications.

Synthesis method of oxiracetam

The invention relates to a synthesis method of (S)-oxiracetam. The method comprises the following steps: (1) carrying out an esterification reaction on alcohol and S-4-amino-3-hydroxybutyrate taken as a starting material to obtain an intermediate I; (2) enabling the intermediate I and halogenated acetic ester to be subjected to a condensation reaction to obtain an intermediate II; (3) carrying out a ring closing reaction on the intermediate II to obtain an intermediate III; and (4) carrying out an ammonolysis reaction on the intermediate III to obtain the target product (S)-oxiracetam. After the synthesis route of the oxiracetam is adopted, the (S)-oxiracetam with more ideal yield of 20% or more is at least obtained; and therefore, a new oxiracetam synthesis route is opened up.

Oxiracetam preparation method

An oxiracetam preparation method comprises the following steps: (a) azidation reaction of 4-chloro-3-hydroxybutyrate as a starting material and an azidation reagent to obtain an give intermediate I; (2) reduction reaction of the intermediate I to obtain an intermediate II; (2) condensation reaction of the intermediate II and a halogenated acetic acid ester to obtain an intermediate III; (3) ring closing reaction of the intermediate III to obtain an intermediate IV; and (4) aminolysis reaction of the intermediate IV to obtain desired product oxiracetam. The desired product oxiracetam with an ideal yield of at least more than 38% can be obtained, and a new oxiracetam synthetic route is opened up.

Oxiracetam synthesis technology

The invention belongs to the field of pharmaceutical chemicals and particularly relates to an oxiracetam synthesis technology, ethyl acetoacetate and glycine are taken as the raw materials, the ethyl acetoacetate is changed into 4-halogeneated ethyl acetoacetate by halogenation reaction, the 4-halogeneated ethyl acetoacetate and glycine ester formed by the glycine are cyclized to form 2,4-dioxo-1-pyrrolidine acetate, and 4-hydroxy-2-oxo-1-pyrrolidineacetamide is obtained after hydrolysis and aminolysis. According to the oxiracetam synthesis technology, the related raw materials are easy to obtain, and the synthesis technology is simple and has good industrial values.

4-HYDROXY-2-OXO-1-PYRROLIDINEACETAMIDE RACEMATE CRYSTAL FORM I AND PREPARATION METHOD THEREFOR

A crystal form I of the racemate of 4-hydroxy-2-oxo-1-pyrrolidine acetamide is prepared by the following steps: dissolving crude racemate of 4-hydroxy-2-oxo-1-pyrrolidine acetamide in a small molecular alcohol solvent to reach supersaturation; heating and stirring overnight at 38-42°C to obtain an suspended sediment; filtering and drying to obtain a crystal. The crystal form I of the racemate of 4-hydroxy-2-oxo-1-pyrrolidine acetamide in the present invention has a high purity which can reach 99.5%.

Process for the production of 4-hydroxy-2-oxopyrrolidin-1-yl-acetamide

Process for the production of 4-hydroxy-2-oxoyrrolidin-1-yl-acetamide, a cerebrally active pharmaceutical agent. A 4-halo-3-alkoxy-butenoic acid ester is reacted with glycine to new intermediate products of the formula: STR1 There is further by acid hydrolysis of the alkoxy group, subsequent hydrogenation, esterification of the carboxyl function and finally conversion to the end product by reaction with ammonia.

New enantioselective synthesis of 4-hydroxy-2-oxopyrrolidine-N-acetamide (oxiracetam) from malic acid

The enantioselective synthesis of oxiracetam has been accomplished from readily available optically active D(+) and L(-) malic acids. the key step of the described method involves the selective reduction of a chiral cyclic diimide; in this way, both enantiomers of 4-hydroxy-2-oxopyrrolidine-N-acetamides were prepared.