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Nefiracetam

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Name

Nefiracetam

EINECS 636-080-4
CAS No. 77191-36-7 Density 1.187 g/cm3
PSA 49.41000 LogP 1.87520
Solubility N/A Melting Point 151-155 °C
Formula C14H18N2O2 Boiling Point 458.5 °C at 760 mmHg
Molecular Weight 246.309 Flash Point 231.1 °C
Transport Information N/A Appearance white to off-white crystalline powder
Safety Risk Codes 22
Molecular Structure Molecular Structure of 77191-36-7 (Nefiracetam) Hazard Symbols HarmfulXn
Synonyms

2-(2-Oxo-1-pyrrolidinyl)-N-(2,6-dimethylphenyl)acetamide;DM 9384;DMMPA;DMPPA;DZL 221;N-(2,6-Dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide;Translon;

Article Data 3

Nefiracetam Synthetic route

50-00-0

formaldehyd

119072-54-7, 2769-71-3

2,6-dimethylphenyl isonitrile

56-12-2

4-amino-n-butyric acid

77191-36-7

nefiracetam

Conditions
ConditionsYield
In 2,2,2-trifluoroethanol at 40℃; for 24h; Ugi Condensation; Inert atmosphere;39%
616-45-5

2-pyrrolidinon

1131-01-7

2-chloro-N-(2,6-dimethylphenyl)acetamide

77191-36-7

nefiracetam

Conditions
ConditionsYield
In nitrogen; water; toluene22.2 g (90%)
With sodium methylate In water; toluene332 g (90%)
In nitrogen; water; toluene22.4 g (91%)
In tert-butyl methyl ether; nitrogen; water2.19 g (89%)

C9H11N3O2

87-62-7

2,6-dimethylaniline

77191-36-7

nefiracetam

Conditions
ConditionsYield
In tetrahydrofuran for 0.5h;24 g
67969-82-8

tetrafluoroboric acid diethyl ether

13755-29-8

sodium tetrafluoroborate

2362-50-7

thianthrene-5-oxide

77191-36-7

nefiracetam

C26H25N2O2S2(1+)*BF4(1-)

Conditions
ConditionsYield
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

77191-36-7

nefiracetam

C26H21F4N2O2S2(1+)

Conditions
ConditionsYield
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

77191-36-7

nefiracetam

C26H21F4N2O2S2(1+)*F6P(1-)

Conditions
ConditionsYield
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%
77191-36-7

nefiracetam

A

5-Hydroxynefiracetam

B

N-(2-hydroxymethyl-6-methyl-phenyl)-2-(2-oxo-pyrrolidin-1-yl)-acetamide

C

4'-hydroxy-nefiracetam

D

3'-hydroxy-nefiracetam

Conditions
ConditionsYield
With NADPH-generating system; rat liver microsome In water at 37℃; for 0.25h; pH=7.4; Enzyme kinetics; Oxidation;
77191-36-7

nefiracetam

A

3-mesyloxy-nefiracetam

B

4-mesyloxy-nefiracetam

Conditions
ConditionsYield
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.
77191-36-7

nefiracetam

C19H22N4O2

Conditions
ConditionsYield
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
77191-36-7

nefiracetam

C22H21N3O4

Conditions
ConditionsYield
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

Nefiracetam Specification

The Nefiracetam is an organic compound with the formula C14H18N2O2. The IUPAC name of this chemical is N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide. With the CAS registry number 77191-36-7, it is also named as 2-(2-Oxo-1-pyrrolidinyl)-N-(2,6-dimethylphenyl)acetamide. The product's classification codes are Central nervous system agents; Drug / Therapeutic Agent; Neuroprotective Agents; Nootropic agents; Protective Agents; Psychotropic drugs; Reproductive Effect. Besides, its cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, and monoaminergic neuronal systems that give antiamnesia effects to the Alzheimer's type and cerebrovascular type of dementia.

Physical properties about Nefiracetam are: (1)ACD/LogP: 1.53; (2)ACD/LogD (pH 5.5): 1.53; (3)ACD/LogD (pH 7.4): 1.53; (4)ACD/BCF (pH 5.5): 8.53; (5)ACD/BCF (pH 7.4): 8.53; (6)ACD/KOC (pH 5.5): 161.45; (7)ACD/KOC (pH 7.4): 161.47; (8)#H bond acceptors: 4; (9)#H bond donors: 1; (10)#Freely Rotating Bonds: 3; (11)Polar Surface Area: 40.62 Å2; (12)Index of Refraction: 1.593; (13)Molar Refractivity: 70.33 cm3; (14)Molar Volume: 207.3 cm3; (15)Polarizability: 27.88×10-24cm3; (16)Surface Tension: 51.6 dyne/cm; (17)Density: 1.187 g/cm3; (18)Flash Point: 231.1 °C; (19)Enthalpy of Vaporization: 71.88 kJ/mol; (20)Boiling Point: 458.5 °C at 760 mmHg; (21)Vapour Pressure: 1.36E-08 mmHg at 25°C.

Preparation: this chemical can be prepared by 1 - (hydroxy methyl) -2-- pyrrolidine ketone and 2,6 - dimethylaniline. The yield is about 76%.

You can still convert the following datas into molecular structure:
(1)SMILES: O=C2N(CC(=O)Nc1c(cccc1C)C)CCC2
(2)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)
(3)InChIKey: NGHTXZCKLWZPGK-UHFFFAOYAF
(4)Std. InChI: InChI=1S/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)
(5)Std. InChIKey: NGHTXZCKLWZPGK-UHFFFAOYSA-N

The toxicity data is as follows:

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
dog LD50 oral > 500mg/kg (500mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX)

LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION
Arzneimittel-Forschung. Drug Research. Vol. 44, Pg. 211, 1994.
mouse LD50 intravenous 421mg/kg (421mg/kg)   United States Patent Document. Vol. #4341790,
mouse LD50 oral 1766mg/kg (1766mg/kg)   United States Patent Document. Vol. #4341790,
rat LD50 oral 1182mg/kg (1182mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX)

LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION
Arzneimittel-Forschung. Drug Research. Vol. 44, Pg. 211, 1994.

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