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

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

• 121-05-1 N',N'-diisopropyl-ethane-1,2-diamine 
• 616-45-5 2-pyrrolidinon 
• 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.

Pramiracetam hydrate crystal and preparation method thereof

The invention relates to the technical field of preparation of compounds, in particular to a pramiracetam hydrate crystal and a preparation method thereof. The preparation method of the pramiracetam dihydrate crystal comprises the following steps: (a) dropwise adding a mixed solution of N-[(2-(diisopropylamino) ethyl)-chloroacetamide and a second organic solvent into a mixed solution of pyrrolidone, alkali and a first organic solvent for reaction, separating to obtain an organic phase, and drying to obtain a pramiracetam crude product; and (b) dropwise adding a fourth organic solvent into the mixture of the crude pramiracetam product, a third organic solvent and water, cooling, stirring, collecting the solid, and drying until the water content of the crystal is 10-12%. And further drying the pramiracetam dihydrate crystal until the water content is 5%-7% to obtain a pramiracetam monohydrate crystal. The method disclosed by the invention is safe, controllable, environment-friendly, high in product yield, high in purity, low in production cost and suitable for industrial production.

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.

Ugi Four-Center Three-Component Reaction as a Direct Approach to Racetams

We report the synthesis of racetams, a diverse class of small molecule drugs, by means of the Ugi four-center three-component reaction (U4C-3CR). For the first time, γ-aminobutyric acid is employed as bifunctional input in the Ugi reaction. This protocol is simple, general, and allows one-pot access to a range of drugs and bioactive small molecules.

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).

N-(Substituted-aminoalkyl)-2-oxo-1-pyrrolidineacetamides

N-(substituted-aminoalkyl)-2-oxo-1-pyrrolidineacetamides which are useful as pharmacological agents, especially cognition activators, are disclosed. They can be produced by reacting a 2-oxo-1-pyrrolidineacetate ester with an appropriate amine.