68497-62-1

Basic information

• Product Name: Pramiracetam
• Synonyms: PRAMIRACETAM;N-(2-(Bis(1-methylethyl)amino)ethyl)-2-oxo-1-pyrrolidineacetamide;Amacetam;N-[2-(Diisopropylamino)ethyl]-2-oxo-1-pyrrolidineacetamide;NeupraMir;PraMistar;ReMen;Vinpotropil
• CAS NO: 68497-62-1
• Molecular Formula: C₁₄H₂₇N₃O₂
• Molecular Weight: 269.38
• EINECS: 1308068-626-2
• Product Categories: Health supplements;APIs;Brain health drug;Nootropic;Health Supplement
• Mol File: 68497-62-1.mol
• Article Data: 6

Chemical Properties

• Melting Point: 47-48°
• Boiling Point: bp0.15 162-164°
• Flash Point: 232.6 °C
• Appearance: white to beige/
• Density: 1.036 g/cm³
• Vapor Pressure: 1.11E-08mmHg at 25°C
• Refractive Index: 1.495
• Storage Temp.: 2-8°C
• Solubility: H2O: soluble10mg/mL, clear
• PKA: 14.76±0.46(Predicted)
• Merck: 14,7706
• CAS DataBase Reference: Pramiracetam(CAS DataBase Reference)
• NIST Chemistry Reference: Pramiracetam(68497-62-1)
• EPA Substance Registry System: Pramiracetam(68497-62-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: UV6264081
• Hazardous Substances Data: 68497-62-1(Hazardous Substances Data)

Usage

Description

Pramiracetam as a pyrrolidones cerebral metabolism improving drug,is a kind of CNS drugs that can help improve memory, anti-forgetful , it is developed by the United States Parke-Davis pharmaceutical companies, with a strong improvement in brain function, enhancing memory, the ability to promote brain alertness, and clinical trials have proved that its activity is 6-13 times of piracetam, 3-4 times of oxiracetam, 1.25 times of aniracetam, and it is toxicity low and well tolerated, it can be used for long-term medication to improve symptoms, and delay Alzheimer-type dementia.Clinically relevant for elderly people attention and memory disorders, benign forgetfulness of aging, senile dementia (Alzheimer's disease) prevention, enhancing memory. Pramiracetam also applies to dilate blood vessels bodybuilding health products additives.

Chemical Properties

white crystals

Uses

Pramiracetam is an inhibitor of PREP and anti-migraine agent. It is a more potent nootropic drug derived from piracetam. Pramiracetam reportedly improved cognitive deficits associated with traumatic brain injuries. It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins.

Definition

ChEBI: Pramiracetam is an organonitrogen compound and an organooxygen compound. It is functionally related to an alpha-amino acid.

Brand name

Remen (ParkeDavis).

InChI:InChI=1/C14H27N3O2/c1-11(2)17(12(3)4)9-7-15-13(18)10-16-8-5-6-14(16)19/h11-12H,5-10H2,1-4H3,(H,15,18)

Synthetic route

2-pyrrolidinon (616-45-5) + N-[2-(di(isopropyl)amino)ethyl]-2-chloroacetamide → pramiracetam (68497-62-1)

Conditions	Yield
Stage #1: 2-pyrrolidinon With sodium methylate In toluene at 105 - 108℃; for 3h; Stage #2: N-[2-(di(isopropyl)amino)ethyl]-2-chloroacetamide In toluene at 60 - 70℃;	89.49%

2-(oxo-pyrrolidin-1-yl)-acetic acid ethyl ester (61516-73-2) + N',N'-diisopropyl-ethane-1,2-diamine (121-05-1) → pramiracetam (68497-62-1)

Conditions	Yield
at 100℃; for 16h;	69%

N',N'-diisopropyl-ethane-1,2-diamine (121-05-1) + N-(6-bromopyridin-2-yl)-2-(2-oxopyrrolidin-1-yl)acetamide → pramiracetam (68497-62-1)

Conditions	Yield
at 110℃; for 11h; Inert atmosphere;

N',N'-diisopropyl-ethane-1,2-diamine (121-05-1) → pramiracetam (68497-62-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 1.67 h / 0 - 15 °C 2.1: sodium methylate / toluene / 3 h / 105 - 108 °C 2.2: 60 - 70 °C View Scheme

pramiracetam (68497-62-1) → pramiracetam monohydrate

Conditions	Yield
With water In cyclohexane at 20 - 50℃; for 1.5h; Solvent;	90.92%

pramiracetam (68497-62-1) → Pramiracetam sulfate

Conditions	Yield
With sulfuric acid In acetonitrile at 0 - 5℃;	84.83%

Upstream product

• 616-45-5 2-pyrrolidinon 
• 121-05-1 N',N'-diisopropyl-ethane-1,2-diamine 
• 61516-73-2 2-(oxo-pyrrolidin-1-yl)-acetic acid ethyl ester 

Downstream Products

• 72869-16-0 Pramiracetam sulfate 

Relevant articles and documents

The preparation method of N, N - diisopropylethylenediamine. Preparation method of

N, N -isopropyl N chloroethylamine hydrochloride and the urotropine are reacted in an organic solvent to obtain N - and N diisopropyltripropylestamine quaternary ammonium salt; and the method comprises the following steps: N - reacting with the urotropine in an organic solvent to obtain the quaternary ammonium salt.2 - N - N. N, N - Diisopropyltriprolol quaternary ammonium salt and concentrated hydrochloric acid were reacted in an organic solvent to give N, N - diisopropylethylamine. To the preparation method, safety risks caused by high-pressure production routes are avoided, the quality risks caused by dimer impurities are avoided, environmental pollution is avoided, raw materials are economical and easy to obtain, production cost is low, and good economic benefits are achieved.

Industrial preparation method of pramiracetam sulfate

The invention relates to the field of preparation of compounds, in particular to an industrial preparation method of pramiracetam sulfate. The method includes: (1) converting N-(2-(diisopropyl)ethyl)-2-chloroacetamide hydrochloride to obtain free amide, and removing moisture in the free amide; (2) reacting solid alkali with alpha-pyrrolidone in a solvent I under the protection of nitrogen, simultaneously distilling alcohol generated by the reaction, then adding a solution prepared from the free amide and the solvent I dropwise, and carrying out reaction to obtain pramiracetam; and (3) preparing pramiracetam and sulfuric acid into pramiracetam sulfate. According to the method, pramiracetam sulfate with excellent quality can be efficiently obtained, and the method has the characteristics oflow cost, high environmental friendliness, no use of dangerous materials, and high process safety, and is beneficial to popularization and application in industrial preparation.

Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl]-2-oxo-1-pyrrolidineacetamides, including pramiracetam

A series of N-[(dialkylamino)alkyl]-2-oxo-1-pyrrolidineacetamides was synthesized. The title compounds reversed electroconvulsive shock (ECS) induced amnesia in mice when administered subsequent to the ECS treatment and were inactive in a general observational test for central nervous system (CNS) activity. Active compounds exhibited an inverted U-shaped dose-response curve. Among the compounds with the broadest dose-response curve, as well as the most potent, were those with the N-[2-[bis(1-methylethyl)amino]ethyl] or 2,6-dimethylpiperidinoethyl residues as amide substituent. The N-(dialkylamino) substituent markedly enhances amnesia-reversal activity, with ethylene providing the optimal chain length. N-[2-[Bis(1-methylethyl)amino]ethyl]-2-oxo-1-pyrrolidineacetamide N(-dialkylamino) substituent was selected for preclinical toxicological evaluation, assigned the investigational number CI-879 and the U.S. adopted name (USAN) pramiracetam. Pramiracetam demonstrated a wide margin of safety in animals and was tolerated in normal human volunteers. It has shown encouraging activity in an open label trial in patients with primary degenerative dementia (PDD or senile dementia of the Alzheimer's type).