864731-61-3

Basic information

• Product Name: 4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide
• Synonyms: 4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide;Fluralaner;4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide
• CAS NO: 864731-61-3
• Molecular Formula: C22H17Cl2F6N3O3
• Molecular Weight: 556.2850992
• EINECS: -0
• Mol File: 864731-61-3.mol

Chemical Properties

• Appearance: /
• Density: 1.51±0.1 g/cm3(Predicted)
• PKA: 12.50±0.46(Predicted)
• CAS DataBase Reference: 4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide(864731-61-3)
• EPA Substance Registry System: 4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide(864731-61-3)

Safety Data

• Hazardous Substances Data: 864731-61-3(Hazardous Substances Data)

Usage

Uses

Used in Veterinary Medicine:
4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide is used as an insecticide and acaricide for the treatment of Sarcoptes scabiei var. canis infestation in dogs. It is effective in controlling fleas and ticks, providing long-lasting protection for pets.
Used in Flea Treatment:
4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide is used as a flea treatment for dogs, offering a convenient and long-lasting solution to control flea infestations. A single oral dose of the compound provides at least twelve weeks of flea and tick control, reducing the need for monthly treatments and improving compliance.
Used in Anti-malarial Research:
4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide has potential as an anti-malarial agent. It has been found to kill disease-spreading mosquitoes when they bite treated individuals, offering a novel approach to malaria control and prevention.
Used in Pharmaceutical Industry:
As a member of the isoxazoline class of compounds, 4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide has potential applications in the development of new drugs for various therapeutic areas. Its unique structure and biological activities make it a promising candidate for further research and development.

Mode of action

Fluralaner inhibits γ-aminobutyric acid (GABA)-gated chloride channels (GABAA receptors) and L-glutamate-gated chloride channels (GluCls). Potency of fluralaner is comparable to fipronil (a related GABA-antagonist insecticide and acaricide).

Pharmacodynamic properties

Fluralaner is an acaricide and insecticide. It is efficacious against ticks (Ixodes spp., Dermacentor spp. and Rhipicephalus sanguineus) and fleas (Ctenocephalides spp.) on the dog. Fluralaner has a high potency against ticks and fleas by exposure via feeding, i.e. it is systemically active on target parasites. Fluralaner is a potent inhibitor of parts of the arthropod nervous system by acting antagonistically on ligand-gated chloride channels (GABA-receptor and glutamate-receptor). In molecular on-target studies on insect GABA receptors of flea and fly, fluralaner is not affected by dieldrin resistance. In in vitro bio-assays, fluralaner is not affected by proven field resistances against amidines (tick), organophosphates (tick, mite), cyclodienes (tick, flea, fly), macrocyclic lactones (sea lice), phenylpyrazoles (tick, flea), benzophenyl ureas (tick), pyrethroids (tick, mite) and carbamates (mite). The product contributes towards the control of the environmental flea populations in areas to which treated dogs have access. Newly emerged fleas on a dog are killed before viable eggs are produced. An in vitro study also demonstrated that very low concentrations of fluralaner stop the production of viable eggs by fleas. The flea life cycle is broken due to the rapid onset of action and long lasting efficacy against adult fleas on the animal and the absence of viable egg production.

Pharmacokinetics

Following oral administration, fluralaner is readily absorbed reaching maximum plasma concentrations within 1 day. Food enhances the absorption. Fluralaner is systemically distributed and reaches the highest concentrations in fat, followed by liver, kidney and muscle. The prolonged persistence and slow elimination from plasma (t1/2 = 12 days) and the lack of extensive metabolism provide effective concentrations of fluralaner for the duration of the inter-dosing interval. Individual variation in Cmax and t1/2 was observed. The major route of elimination is the excretion of unchanged fluralaner in faeces (~90% of the dose). Renal clearance is the minor route of elimination.

Drug interactions

Fluralaner is highly bound to plasma proteins and might compete with other highly bound drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) and the cumarin derivative warfarin. Incubation of fluralaner in the presence of carprofen or warfarin in dog plasma at maximum expected plasma concentrations did not reduce the protein binding of fluralaner, carprofen or warfarin. During clinical field testing, no interactions between Bravecto chewable tablets for dogs and routinely used veterinary medicinal products were observed.

Overdosage

No adverse reactions were observed following oral administration to puppies aged 8–9 weeks and weighing 2.0–3.6 kg treated with overdoses of up to 5 times the maximum recommended dose (56 mg, 168 mg and 280 mg fluralaner/kg bodyweight) on three occasions at shorter intervals than recommended (8-week intervals). There were no findings on reproductive performance and no findings of concern on offspring viability when fluralaner was administered orally to Beagle dogs at overdoses of up to 3 times the maximum recommended dose (up to 168 mg/kg bodyweight of fluralaner). The veterinary medicinal product was well tolerated in Collies with a deficient multidrug-resistanceprotein 1 (MDR1 -/-) following single oral administration at 3 times the recommended dose (168 mg/kg bodyweight). No treatment-related clinical signs were observed.

Upstream product

• 753-90-2 trifluoroethylamine 
• 864725-22-4 1,3-dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene 
• 864736-32-3 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester 
• 55860-35-0 4-acetyl-2-methyl benzoic acid 
• 359821-38-8 2-ammonia-N-(2,2,2-trifluoroethyl)acetamide 
• 130336-16-2 3,5-dichloro-2,2,2-trifluoroacetophenone 
• 930110-37-5 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzonitrile 
• 1138444-80-0 3-methyl-4-cyanoacetophenone 
• 180082-96-6 4-bromo-3-methylbenzaldehyde oxime 
• 108-38-3 m-xylene 
• 78775-11-8 3-methyl-4-bromobenzaldehyde 
• 583-70-0 1-bromo-2,4-dimethylbenzene 
• 27613-35-0 4-formyl-2-methylbenzonitrile 
• 1036715-60-2 4-acetyl-2-methylbenzoic acid methyl ester 

Relevant articles and documents

PROCESS FOR PREPARATION OF ISOXAZOLINE SUBSTITUTED BENZAMIDE COMPOUND

The invention relates to process for the preparation of isoxazoline-substituted benzamide compound and intermediates thereof. The invention also relates to process for the preparation of Fluralaner and intermediates thereof.

Synthetic method of fluralana

According to the method, 2-methyl-5-bromobenzoic acid is adopted as a raw material, and Suzuki coupling reaction, condensation reaction, dehydration cyclization reaction and amide condensation reaction are performed to finally obtain the fluralan. According to the synthesis method, the reaction cost is reduced, the yield is improved, and the reaction period is shortened.

PROCESS FOR PREPARING FLURALANER

The invention relates to an improved process for the synthesis of Fluralaner in an efficient and economical way.

Synthesis of fluralaner

The invention relates to synthesis of fluralaner, and the key step of synthesis relates to preparation of the fluralaner through reaction of 4-(5-(3, 5-dichlorophenyl)-5-(trifluoromethyl)-4, 5-dihydroisoxazole-3-yl)-2-methyl-benzonitrile and 2-amino-N-(2, 2, 2-trifluoroethyl) acetamide under the action of Zn(OTf)2/hydroxylamine hydrochloride.

Method for preparing fluralana intermediate, prepared intermediate and application of fluralana intermediate

A method for preparing a fluralana intermediate, provided by the invention, comprises the following steps: carrying out nucleophilic addition reaction on 1-(3, 5-dichlorophenyl)-2, 2, 2-trifluoroethanone, carrying out acidolysis, reacting with a Grignard reagent, carrying out oxidation, carrying out oxidation cyclization reaction, reacting with hydroxyl(toluenesulfonyloxy)benzene iodide, and reacting with a trimethoxyphosphorus solution to finally generate the fluralan. In the preparation process, a catalyst and dimethoxy zinc are not needed, ultralow-temperature reaction conditions of -78 DEG C are not needed, operation is easy and convenient, meanwhile, reagents such as ozone and dimethyl sulfide which are harmful to the environment are replaced, and the method is more environmentally friendly. The invention also provides the intermediate for preparing the fluralan.

Fluorine thramine intermediate and method for preparing flumbine by using same

The invention discloses a fluororesonide intermediate and a method for preparing the same, and a fluororesonide intermediate -5. Routes include the use of m-xylene as starting materials, halogenation. Oxidation reaction The intermediate -5 is further obtained by hydroximation, cyanolation, hydrolysis reaction or cyanation, oximation, and hydrolysis reaction. As some examples of the present invention, synthetic routes were increased 2 steps from 5 steps in the prior art, but surprisingly high overall yields were obtained and the purity of intermediate -5 was significantly increased. , The starting material of the intermediate -5 is prepared from high 4 - bromo -2 - methylbenzoic acid to low-priced m-xylene, so that the cost of the intermediate -5 is greatly reduced. , The reaction condition is mild, the synthesis difficulty is low, and the environment is more environmentally friendly.

PROCESS FOR PURIFICATION OF FLURALANER

The present invention relates to a process for purification of Fluralaner of formula (I). The present invention further relates to a process for purification of Fluralaner of formula (I) with purity more than 99%, in simple, economic and commercially viable manner.

Preparation method of isoxazoline insecticide

The invention relates to a preparation method of an isoxazoline insecticide, which relates to the technical field of chemical industry, and comprises the following steps: 1) coupling reaction: mixingan intermediate 1 with nitromethane in a solvent, adding a palladium catalyst and a ligand to carry out catalytic coupling, reacting, and separating and purifying to obtain an intermediate 2; 2) cyclization reaction: mixing the intermediate 2 and an intermediate 3, adding the mixture into a mixed solution of a dehydrating agent and alkali, carrying out full cyclization reaction, and purifying to obtain an intermediate 4; and 3) condensation reaction: mixing the intermediate 4 and an intermediate 5, adding a condensing agent, carrying out full condensation reaction, and carrying out separationand purification to obtain an isoxazoline compound 6. The method has the advantages of short reaction route, accessible raw materials, fewer three wastes and high purity of the purified product, and is suitable for industrial production.

PROCESS FOR PREPARATION OF OPTICALLY ENRICHED ALDOL COMPOUNDS

The present invention relates to a process for preparing benzylic amidesof formula (I) wherein the variables are as defined in the specification, and the shown enantiomer has at least 50 % ee; by condensation of a ketone o formula (II) with an acetyl compound of formula (III) in the presence of a catalystof formula (IV) wherein the variables are as defined in the specification.

Synthetic method of isoxazoline anthelmintic

The invention belongs to the technical field of chemical drug synthesis, and particularly relates to a synthesis method of an isoxazoline anthelmintic. The method is characterized in that the isoxazoline anthelmintic is fluralaner, and the method includes