Modafinil Chemical Properties

Melting point:

164-166°C

Boiling point:

559.1±50.0 °C(Predicted)

Density 

1.283±0.06 g/cm3(Predicted)

Flash point:

2℃

storage temp. 

Store at +4°C

solubility 

DMSO: 18 mg/mL, soluble

pka

14.88±0.40(Predicted)

form 

white solid

color 

white

BCS Class

4

CAS DataBase Reference

68693-11-8(CAS DataBase Reference)

Safety Information

Hazard Codes 

T+,Xn,F

Risk Statements 

26/27/28-36-20/21/22-11

Safety Statements 

24/25-45-36/37/39-22-36/37-16

RIDADR 

UN 1648 3 / PGII

WGK Germany 

3

HS Code 

29309090

Hazardous Substances Data

68693-11-8(Hazardous Substances Data)

MSDS

• Language:English Provider:2-[(Diphenylmethyl)sulfinyl]-acetamide
• Language:English Provider:SigmaAldrich

Modafinil Usage And Synthesis

Description

Marketed as a wakefulness promoting agent, modafinil belongs to the group of medicines known as central nervous system (CNS) stimulants, which is commonly used to promote wakefulness and reduce excessive daytime sleepiness in patients with narcolepsy, obstructive sleep apnea, hypopnea syndrome, shift-work sleep disorder or circadian rhythm sleep disorder. Besides, recently studies have showed that modafinil may be effective to help cocaine addicts fight against their addiction.
The sleepiness-preventing effects of modafinil functions by stimulating certain parts of the brain, in which the neurons are activated by modafinil. It binds to the dopamine reuptake pump so as to inhibit the reuptake of dopamine from the cell, while the extracellular dopamine increases, thus preventing drowsiness and keeping people from falling asleep.

References

https://en.wikipedia.org/wiki/Modafinil
http://bodyandhealth.canada.com/drug/getdrug/apo-modafinil
https://www.drugbank.ca/drugs/DB00745

Description

Modafinil, a centrally active α₁-adrenergic agonist, was marketed in France as a psychostimulant for the treatment of narcolepsy and idiopathic hypersomnia including Gelineau's syndrome. In monkeys, modafinil was found to induce potent behavioral stimulation and awakening without stereotyped behavior. In narcoleptic patients, modafinil reduces the daily number of sleep attacks significantly and markedly improves performance. The mechanism of action for its locomotor effects was reported to be due to the stimulation of the central α₁-adrenergic system, opposite to amphetamine and methylphenidate, which act mainly by dopaminergic mechanisms. Modafinil has been reported to exhibit minimal peripheral side effects at therapeutic doses and appears to have low abuse potential. The use of modafinil in the treatment of cerebral infarction and ischemia has been claimed.

Chemical Properties

Crystalline Solid

Originator

Lafon (France)

Uses

ACE inhibitor, antihypertensive

Uses

Modafinil is an α-1-adrenergic agonist. Modafinil is a CNS stimulant; psychostimulant that displays neuroprotective and antiparkinsonian activity in a primate model of Parkinson's disease.

Uses

A central nervous system vigilance promoting agent. Possesses neuroprotective properties. This is a controlled substance (stimulant)

Definition

ChEBI: 2-[(diphenylmethyl)sulfinyl]acetamide is a sulfoxide that is dimethylsulfoxide in which two hydrogens attached to one of the methyl groups are replaced by phenyl groups, while one hydrogen attached to the other methyl group is replaced by a carbamoyl (aminocarbonyl) group. It is a sulfoxide and a monocarboxylic acid amide.

Manufacturing Process

To 19.5 g (0.076 mol) of benzhydrylthioacetic acid in 110 ml of benzene was added drop by drop 19 ml of thionyl chloride. The mixture was refluxed 1 hour, benzene and the excess thionyl chloride was evaporated. A clear orange oil of benzhydrylthioacetyl chloride is obtained.
The benzhydrylthioacetyl chloride in 100 ml of methylene chloride was added drop by drop to 35 ml of ammonia in 40 ml of water. Once the addition is complete, the organic phase is washed with a dilute solution of soda and dried over Na2SO4, the solvent is evaporated and the residue is taken up in diisopropyl ether, the benzhydrylthioacetamide is crystallised. 16.8 g of product (yield 86%) are obtained. Melting point 110°C.
14.39 g (0.056) of benzhydrylthioacetamide are placed in a balloon flask and 60 ml of acetic acid and 5.6 ml of H2O2 are added. The mixture is left for one night at 40°C and about 200 ml of water are then added; the CRL 40476 crystallises. By recrystallisation from methanol 11.2 g of benzhydrylsulphinylacetamide are obtained. Yield: 73%, melting point 164- 166°C.
The synthesis of benzhydrylsulphinylacetamide (CRL 40476) on an industrial scale.
1.003 kg of thiourea is dissolved in 5.72 L of 48% hydrobromic acid and 0.880 L of water in a 20 L reaction vessel. The mixture is heated to 60°C and 2.024 kg of benzhydrol are introduced. The temperature is increased to 95°C and the contents of the vessel are allowed to cool to room temperature. The crystals are filtered off and washed with water. They are made into a paste again in 5.5 L of water and this is introduced into a 20 L reaction vessel with 3.5 L of soda lye (d = 1.33). The mixture is heated to 70°C and 1144 g of chloroacetic acid dissolved in 2.2 L of water are passed in slowly. After cooling the benzhydrylthioacetic acid is obtained, but is not isolated.
1.430 L of hydrogen peroxide are passed in over 3 hours at 30°C into the above reaction mixture. 22 L of water are then passed in, the insoluble material is filtered off and acidification is carried out with hydrochloric acid (d = 1.18). Filtration, washing with water to reform a paste and drying without heat are carried out. In this way, the benzhydrylsulphinylacetic acid is obtained.
The above acid is placed in a 20 L reaction vessel with 6 L of water. 1.1 liters of soda lye (d = 1.33) and 1.848 kg of sodium bicarbonate are added. 2.1 L of dimethyl sulfate are added. After one hour, crystallisation is induced. Filtration, drying without heat and washing are carried out. Methyl benzhydrylsulphinylacetate is obtained.
1 kg of methyl benzhydrylsulphinylacetate is dissolved in 3.5 liters of anhydrous methanol in a 10-liter balloon flask. NH3 is bubbled in at a high rate of flow for 1 hour, and then left in contact for 4 hours. Filtration, drying without heat and washing with water are then carried out. By recrystallisation from a mixture of water and methanol (4:1) and then from a mixture of water and methanol (9:1) and drying under reduced pressure, CRL 40476 is obtained in the form of a white crystalline powder; melting point 164-166°C. Total yield (calculated from the benzhydrol): 41%.

brand name

Provigil (Cephalon);Modiodal.

Therapeutic Function

Psychostimulant

General Description

Modafinil (Provigil) has overall wakefulness-promotingproperties similar to those of central sympathomimetics. It isconsidered an atypical α1-norepinephrine (NE) receptorstimulant and is used to treat daytime sleepiness in narcolepsypatients. Adverse reactions at therapeutic doses arereportedly not severe and may include nervousness, anxiety,and insomnia. Modafinil is used by oral administration.

Biological Activity

Psychostimulant that displays neuroprotective and antiparkinsonian activity in a primate model of Parkinson's disease. Promotes vigilence and wakefulness without the central and peripheral side effects associated with conventional dopaminergic psychostimulants. Mechanism of action is not fully understood, possibly via modulation of catecholamine/GABAergic neurotransmission.

Clinical Use

Excessive daytime drowsiness associated with narcolepsy and obstructive sleep apnoea

Drug interactions

Potentially hazardous interactions with other drugs
Ciclosporin: reduced ciclosporin concentration.
Cytotoxics: concentration of bosutinib possibly reduced - avoid.
Guanfacine: concentration of guanfacine possibly reduced - avoid.
Oestrogens: metabolism accelerated (reduced contraceptive effect).
Ulipristal: possibly reduces contraceptive effect of ulipristal - avoid

Metabolism

Metabolised in the liver, partly by the cytochrome P450 isoenzymes CYP3A4 and CYP3A5; two major metabolites have been identified: acid modafinil and modafinil sulfone, both of which are inactive. Excretion is mainly through the kidneys.

storage

+4°C

Modafinil(68693-11-8)Related Product Information

• Acetamide
• N-Methylacetamide
• Acetaminophen
• N-Acetylsulfanilyl chloride
• N,N-Dimethylacetamide
• 2-Phenylacetamide
• Modafinil
• (R)-Modafinil Carboxylate Methyl Ester
• Armodafinil
• SULFOXIDE
• Modafinil-D5,(R)-(-)-Modafinil-d5,(R)-Modafinil-d5,(S)-(+)-Modafinil-d5,(S)-Modafinil-d5
• Modafinil Acid
• (R)-Modafinil Carboxylate (S)-a-Methylbenzenemethanamine Salt
• MODAFINIL FOR SYSTEM SUITABILITY
• Modafinil-d5(Mixture of diastereomers)
• Modafinil Carboxylate-d5,Modafinil-d5 Acid
• (R)-(-)-Modafinil Acid,(R)-Modafinil Carboxylate
• (S)-(+)-Modafinil,(S)-Modafinil