77191-36-7

Basic information

• Product Name: Nefiracetam
• Synonyms: n-(2,6-dimethylphenyl)-2-oxo-1-pyrrolidineacetamide;NEFIRACETAM;2-oxo-1-pyrrolidinylaceticacid,2,6-dimethylanilide;dm9384;dmppa;n-(2,6-dimethylphenyl)-2-oxo-1-pyrrolidineacetamid;DM-9384, (2-(2-Oxopyrrolidin-1-yl)-N-(2,6-dimethylphenyl)-acetamide);DMMPA
• CAS NO: 77191-36-7
• Molecular Formula: C₁₄H₁₈N₂O₂
• Molecular Weight: 246.3
• EINECS: 1308068-626-2
• Product Categories: Nootropic;Smart drug;Pharmaceutical intermediate;TRANSLON
• Mol File: 77191-36-7.mol
• Article Data: 3

Chemical Properties

• Melting Point: 151-155°C
• Boiling Point: 458.5 °C at 760 mmHg
• Flash Point: 231.1 °C
• Appearance: white to off-white/
• Density: 1.187 g/cm³
• Vapor Pressure: 1.36E-08mmHg at 25°C
• Refractive Index: 1.593
• Storage Temp.: Store at RT
• Solubility: DMSO: >5mg/mL
• PKA: 13.77±0.70(Predicted)
• Merck: 14,6439
• CAS DataBase Reference: Nefiracetam(CAS DataBase Reference)
• NIST Chemistry Reference: Nefiracetam(77191-36-7)
• EPA Substance Registry System: Nefiracetam(77191-36-7)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: UX9655650
• Hazardous Substances Data: 77191-36-7(Hazardous Substances Data)

Usage

Uses

Nefiracetam improves post-ischemia evoke-nonconvulsive seizure by altering pro-inflammatory cytokines.

Biological Activity

Cognitive enhancer that displays various pharmacological effects. Activates L/N-type calcium channels, cholinergic, monoaminergic and GABAergic systems. Displays potent neuroprotective action in the retinal ischemia-reperfusion model in vivo .

InChI:InChI=1/C14H18N2O2/c1-10-5-3-6-11(2)14(10)15-12(17)9-16-8-4-7-13(16)18/h3,5-6H,4,7-9H2,1-2H3,(H,15,17)

Synthetic route

formaldehyd (50-00-0) + 2,6-dimethylphenyl isonitrile (119072-54-7, 2769-71-3) + 4-amino-n-butyric acid (56-12-2) → nefiracetam (77191-36-7)

Conditions	Yield
In 2,2,2-trifluoroethanol at 40℃; for 24h; Ugi Condensation; Inert atmosphere;	39%

2-pyrrolidinon (616-45-5) + 2-chloro-N-(2,6-dimethylphenyl)acetamide (1131-01-7) → nefiracetam (77191-36-7)

Conditions	Yield
In nitrogen; water; toluene	22.2 g (90%)
With sodium methylate In water; toluene	332 g (90%)
In nitrogen; water; toluene	22.4 g (91%)
In tert-butyl methyl ether; nitrogen; water	2.19 g (89%)

C9H11N3O2 + 2,6-dimethylaniline (87-62-7) → nefiracetam (77191-36-7)

Conditions	Yield
In tetrahydrofuran for 0.5h;	24 g

tetrafluoroboric acid diethyl ether (67969-82-8) + sodium tetrafluoroborate (13755-29-8) + thianthrene-5-oxide (2362-50-7) + nefiracetam (77191-36-7) → C26H25N2O2S2(1+)*BF4(1-)

Conditions	Yield
Stage #1: tetrafluoroboric acid diethyl ether; thianthrene-5-oxide; nefiracetam With trifluoroacetic anhydride In acetonitrile at -40 - 25℃; for 6h; Schlenk technique; Stage #2: sodium tetrafluoroborate In dichloromethane; water	74%

2,3,7,8-tetrafluorothianthrene-S-oxide + nefiracetam (77191-36-7) → C26H21F4N2O2S2(1+)

Conditions	Yield
With 2,3,7,8-tetrafluorothianthrene; boron trifluoride diethyl etherate; trifluoroacetic anhydride In acetonitrile at 0 - 25℃; regioselective reaction;	63%

2,3,7,8-tetrafluorothianthrene-S-oxide + nefiracetam (77191-36-7) → C26H21F4N2O2S2(1+)*F6P(1-)

Conditions	Yield
Stage #1: 2,3,7,8-tetrafluorothianthrene-S-oxide; nefiracetam With boron trifluoride diethyl etherate; trifluoroacetic anhydride In acetonitrile at 0 - 25℃; for 4h; Sealed tube; Stage #2: With ammonium hexafluorophosphate In dichloromethane; water	63%

nefiracetam (77191-36-7) → 5-Hydroxynefiracetam + N-(2-hydroxymethyl-6-methyl-phenyl)-2-(2-oxo-pyrrolidin-1-yl)-acetamide + 4'-hydroxy-nefiracetam + 3'-hydroxy-nefiracetam

Conditions	Yield
With NADPH-generating system; rat liver microsome In water at 37℃; for 0.25h; pH=7.4; Enzyme kinetics; Oxidation;

nefiracetam (77191-36-7) → 3-mesyloxy-nefiracetam + 4-mesyloxy-nefiracetam

Conditions	Yield
With bis(methanesulfonyl)peroxide at 23℃; for 24h; Inert atmosphere; Schlenk technique; Overall yield = 65%; Overall yield = 112 mg;	A 39 %Spectr. B 26 %Spectr.

nefiracetam (77191-36-7) → C19H22N4O2

Conditions	Yield
Multi-step reaction with 2 steps 1: trifluoroacetic anhydride / acetonitrile / 6 h / -40 - 25 °C / Schlenk technique 2: [(2-di-tert-butylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1’-biphenyl)-2-(2’-amino-1,1‘-biphenyl)]palladium(II) methanesulfonate; 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran / 16 h / 70 °C / Inert atmosphere; Glovebox; Sealed tube View Scheme

nefiracetam (77191-36-7) → C22H21N3O4

Conditions	Yield
Multi-step reaction with 2 steps 1: trifluoroacetic anhydride / acetonitrile / 6 h / -40 - 25 °C / Schlenk technique 2: tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; tetrakis(acetonitrile)copper(I)tetrafluoroborate; tetramethyl ammoniumhydroxide / acetonitrile; dimethyl sulfoxide / 8 h / 15 °C / Inert atmosphere; Irradiation View Scheme

MANDELIC ACID (611-71-2, 611-72-3, 17199-29-0, 90-64-2) + nefiracetam (77191-36-7) → C14H18N2O2*C8H8O3 + C14H18N2O2*C8H8O3

Conditions	Yield
Stage #1: MANDELIC ACID; nefiracetam In acetonitrile at 23℃; for 24h; Stage #2: In acetonitrile at 17℃; Resolution of racemate;

MANDELIC ACID (611-71-2, 611-72-3, 17199-29-0, 90-64-2) + nefiracetam (77191-36-7) → C14H18N2O2*C8H8O3

Conditions	Yield
In methanol Milling;

(R)-Mandelic Acid (611-71-2) + nefiracetam (77191-36-7) → C14H18N2O2*C8H8O3

Conditions	Yield
In ethyl acetate at 23℃; for 48h; Solvent;

(S)-Mandelic acid (17199-29-0) + nefiracetam (77191-36-7) → C14H18N2O2*C8H8O3

Conditions	Yield
In ethyl acetate at 23℃; for 48h; Solvent;

Upstream product

• 87-62-7 2,6-dimethylaniline 
• 50-00-0 formaldehyd 
• 119072-54-7 2,6-dimethylphenyl isonitrile 
• 56-12-2 4-amino-n-butyric acid 
• 616-45-5 2-pyrrolidinon 
• 1131-01-7 2-chloro-N-(2,6-dimethylphenyl)acetamide 

Relevant articles and documents

Preparation method of drug niracetam for treating's disease (by machine translation)

The invention belongs to the field, and particularly discloses a preparation method. of medicine for treating's disease. By N' N N-dicarbonyl imidazole (CDI) to activate carboxyl in 2 - oxopyrrolidine acetic acid, the reaction activity, the reaction rate, the side reaction are reduced, the obtained product yield is high, the purity is high, the production cost, and the industrial production. (by machine translation)

Process for preparing pyrrolidinylacetamide derivatives

A process for preparing a 2-(1-pyrrolidinyl)acetamide derivative useful as a cerebral function improving agent is disclosed, comprising reacting a halogenoacetamide derivative with substituted or unsubstituted 2-pyrrolidinone, the halogenoacetamide derivative being prepared by reacting an amine and a halogenoacetyl chloride. High yields of the intermediate compound as well as the final product are attained at low cost.