91714-93-1

Basic information

• Product Name: Bromfenac sodium
• Synonyms: 2-AMINO-3-(4-BROMOBENZOYL)PHENYLACETIC ACID SODIUM;2-Amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt;Bromfenac sodium;Sodium [2-amino-3-(4-bromobenzoyl)phenyl]acetate;Ahr 10282b;Benzeneacetic acid, 2-amino-3-(4-bromobenzoyl)-, monosodium salt;Bronuck;2-{2-aMino-3-[(4-broMophenyl)carbonyl]phenyl}acetic acid
• CAS NO: 91714-93-1
• Molecular Formula: C₁₅H₁₁BrNO₃*Na
• Molecular Weight: 356.15
• EINECS: 1806241-263-5
• Product Categories: Aromatic Phenylacetic Acids and Derivatives;Inhibitors
• Mol File: 91714-93-1.mol

Chemical Properties

• Melting Point: 285 ºC
• Boiling Point: 562.2 °C at 760 mmHg
• Flash Point: 293.8 °C
• Appearance: faint yellow to dark yellow/
• Vapor Pressure: 1.77E-13mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: H2O: ≥5mg/mL
• CAS DataBase Reference: Bromfenac sodium(CAS DataBase Reference)
• NIST Chemistry Reference: Bromfenac sodium(91714-93-1)
• EPA Substance Registry System: Bromfenac sodium(91714-93-1)

Safety Data

• Hazard Codes: N
• Statements: 50
• Safety Statements: 61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 91714-93-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Bromfenac sodium is used as an analgesic and anti-inflammatory agent for reducing prostaglandin production through inhibition of cyclooxygenase.
Used in Ophthalmology:
Bromfenac sodium is used as a postoperative anti-inflammatory agent for the treatment of inflammation following cataract surgery when administered as a 0.9% topical solution on a tapering schedule for 24 weeks.
Used in Research:
Bromfenac sodium is used to study its ability to bind to melanin, in the synthesis of bromfenac indolinone standard, and to analyze its permeability in porcine conjunctiva.

Manufacturing Process

Reaction of (2-aminophenyl)-(4-bromophenyl)-methanone with methylsulfanylacetic acid ethyl ester and tert-butyl hypochlorite gives a corresponding sulfonium salt. This salt was transformed to initially to the betaine. Electrocyclic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid. Internal ester-amine interchange leads then to 4-bromophenyl-(3-(methylthio)indolin-7-yl)methanone. The thiomethyl group is then removed with Raney nickel to give 4-bromophenyl- (indolin-7-yl)methanone. Saponification of this intermediate affords the (2- amino-3-(4-bromobenzoyl)-phenyl)-acetic acid (Bromfenac). In practice it is usually used as sodium salt.

Therapeutic Function

Analgesicá Antiinflammatory

Biochem/physiol Actions

Bromfenac exhibits antipyretic and prostaglandin synthetase inhibiting properties. It has therapeutic properties against the reduction of ocular pain and inflammation in postoperative cataract patients. Bromfenac acts as an effective agent against allergic conjunctivitis. It has the potential to treat acute muscle pain, osteoarthritis, and rheumatoid arthritis.

InChI:InChI=1/C15H12BrNO3.Na.H2O/c16-11-6-4-9(5-7-11)15(20)12-3-1-2-10(14(12)17)8-13(18)19;;/h1-7H,8,17H2,(H,18,19);;1H2/q;+1;/p-1

Upstream product

• 91713-91-6 7-(4-bromobenzoyl)-1,3-dihydro-2H-indol-2-one 
• 91714-50-0 7-(4-bromobenzoyl)-1-hydro-indole 
• 91714-94-2 bromfenac 
• 1140-17-6 2-amino-4'-bromobenzophenone 
• 92433-07-3 N-(2-(4'-bromobenzoyl)phenyl)acetamide 
• 121-62-0 N-acetylsulfanilic acid 
• 578-54-1 ortho-ethylaniline 
• 586-75-4 4-chlorobenzoyl chloride 
• 619-42-1 4-methoxycarbonylphenyl bromide 
• 40649-38-5 2-methoxycarbonyl-6-methoxycarbonylmethylcyclohexanone 
• 103205-34-1 2-(2-acetamidophenyl)acetic acid 
• 3342-78-7 2-(2-aminophenyl)acetic acid 

Downstream Products

• 91713-91-6 7-(4-bromobenzoyl)-1,3-dihydro-2H-indol-2-one 

Relevant articles and documents

Novel synthesis method of bromfenac sodium

The novel synthesis method is characterized by comprising the following steps: taking o-aminophenylacetic acid as a starting raw material, and performing acylation reaction to obtain the intermediate I. The intermediate I is subjected to a sulfonation reaction to obtain an intermediate II. The intermediate II is reacted with p-bromobenzoyl chloride to give an intermediate III. The intermediate III is hydrolyzed to give bromfenac. The final finished product bromfenac sodium is obtained by reacting bromfenac and sodium hydroxide. The method has the beneficial effects that an indole ring-containing impurity generated due to a synthetic method in the prior art is avoided. The problem of exceeding standard of final finished product pH caused by using phosphoric acid or glacial acetic acid to produce acid salt in the prior art is avoided.

Refining method and preparation method of bromfenac sodium sesquihydrate

The invention relates to a refining method and preparation method of bromfenac sodium sesquihydrate. Specifically, the invention provides the refining method comprising the steps: (a) regulating pH ofan aqueous solution of a compound represented by the formula 2 to pH of 2-3 with an acidity regulator, and thus obtaining a regulated aqueous solution; (b) extracting the regulated aqueous solution obtained in the step (a) with a first solvent and separating the solution to obtain an organic phase; and (c) regulating the pH value of the organic phase obtained in the step (b) by using an alkalinity regulator so as to separate out a solid, namely the bromfenac sodium sesquihydrate, from the organic phase. The method has the advantages that the alkalinity of the bromfenac sodium sesquihydrate can be accurately controlled, the purity and content of the bromfenac sodium sesquihydrate are higher than those of a recrystallization method, the recrystallization heating and cooling process is avoided, operation is simplified, energy consumption is reduced, long-time stirring crystallization is not needed, the preparation period is shortened, and the yield is increased.

Simple preparation method of bromfenac sodium

The invention relates to a simple preparation method of bromfenac sodium, comprising the following steps: carrying out a condensation reaction between bromophenylacetonitrile and 2-nitrophenylacetic acid under the action of alkali to prepare 7-(4-bromophenyl)-3-carboxymethylbenzo [c] isoxazole (IV), carrying out a reduction reaction on the compound as shown in the formula IV, and alkalizing with sodium hydroxide for salifying to prepare bromfenac sodium. The method has the advantages of cheap and easily available raw materials, simple route, easy operation, low product cost, good product purity and high yield, and is suitable for industrial production.

Preparation method of bromfenac sodium

The invention provides a preparation method of bromfenac sodium (I). The method comprises the following steps: p-bromobenzoate (II) and 2-alkoxycarbonyl-6-alkoxycarbonylmethylcyclohexanone (III) whichare used as raw materials are condensed under the action of an alkali, and then are hydrolyzed and decarboxylated to obtain 2-[3-(4-bromobenzoyl)-2-oxocyclohexyl]acetic acid (IV), the 2-[3-(4-bromobenzoyl)-2-oxocyclohexyl]acetic acid (IV) and a halogenating reagent undergo a substitution reaction to obtain 2-[1,3-dihalo-3-(4-bromobenzoyl)-2-oxocyclohexyl]acetic acid (V), the 2-[1,3-dihalo-3-(4-bromobenzoyl)-2-oxocyclohexyl]acetic acid (V) and ammonia undergo an ammoniation reaction, then an elimination reaction is carried out under the action of the alkali to obtain bromfenac (VI), and the bromfenac is salified to obtain the bromfenac sodium (I). The method has the advantages of cheap and easily available raw materials, simple process flow, mild reaction conditions, easiness in realization, low cost;, little generated wastewater, safety, greenness, environmental protection, stable intermediate, high reaction activity and selectivity, few side reactions, high yield and purity of the obtained bromfenac sodium, and suitableness for industrial production.

Preparation method of bromfenac sodium intermediate

The invention belongs to the field of medicinal chemistry, and particularly relates to a preparation method of bromfenac sodium and an intermediate thereof. The method comprises the steps that a new solvent system is adopted for preparing the intermediate, generation of brick-red by-products is avoided, the impurity content in the intermediate is greatly reduced, and the purity and yield of the intermediate are improved.

Preparation method of bromfenac sodium

The invention discloses a preparation method of bromfenac sodium. O-ethylaniline and p-bromobenzoyl chloride are used as initiators and a series of reactions of Fourier reaction, substitution and oxidation salification are carried out, so that bromfenac sodium is obtained. The method has the advantages that the process is simple, post-treatment is simple and convenient, dangerous catalytic hydrogenation is avoided, the use of a strong corrosive reagent of phosphoric acid is avoided, the reaction condition is mild, the reaction yield is high, the product quality is high, the process cost is low, and the method is green and energy-saving.

A bromide fragrant preparation method of sodium and important intermediates

The invention provides a preparation and refining method of bromfenac sodium. The method has the advantages that the reaction conditions are mild, the operation is simple, and the obtained product is high in purity, high in yield and low in cost and can be industrially produced easily.

A preparation method of a bromfenac sodium sesquihydrate compound

A preparation method of a bromfenac sodium sesquihydrate compound is disclosed. The method includes steps of subjecting a compound of a formula 3 and an aqueous solution of sodium hydroxide to a hydrolysis reaction; directly subjecting the reaction solution to suction filtration after the reaction is completed; collecting a filtrate; adding sodium chloride or sodium bicarbonate into the filtrate;washing solid precipitated after the sodium chloride or sodium bicarbonate is added with saturated brine and acetone; performing recrystallization using a mixed solvent that is water/acetone, water/glycol dimethyl ether or water/ethylene glycol; and washing the solid obtained by recrystallization with acetone to obtain the bromfenac sodium sesquihydrate compound that is the compound of the formula4. The method is simple to operate and stable in process, and the obtained bromfenac sodium sesquihydrate compound is yellow solid with extremely high purity.

Method for synthesizing bromfenac sodium

The invention discloses a method for synthesizing bromfenac sodium. The method comprises the steps of (1) carrying out acetylation reaction on 2-amino-4'-bromo benzophenone as a raw material to obtain a formula III: N-(2-(4'-bromo benzoyl)phenyl)acetamide; (2) reacting the N-(2-(4'-bromo benzoyl)phenyl)acetamide in a formula IV with a halogen acetylation reagent to obtain a formula V: N-acetyl-N-(2-(4'-bromo benzoyl)phenyl)-2-haloacetamide; (3) carrying out friedel-crafts reaction on the N-acetyl-N-(2-(4'-bromo benzoyl)phenyl)-2-haloacetamide to obtain a formula IV: 1-acetyl-7-(4-bromo-benzoyl chloride) indoline-2-ketone; and (4) finally hydrolyzing the 1-acetyl-7-(4-bromo-benzoyl chloride) indoline-2-ketone to obtain a target product. The method is low in cost, reaction is easy to control, post-treatment is simple, the overall yield is high, the method is economical and environmentally friendly, and a novel method for synthesizing the bromfenac sodium is provided.

A method for preparation of sodium bromine fragrance

The invention relates to a preparation method of bromfenac sodium. The preparation method comprises the following steps of (a) reacting a compound represented by a formula (V) with an electrophilic substitutional reagent in the presence of N,N-dimethylformamide or dimethyl sulfoxide to obtain a compound represented by a formula (IV), (b) adding the compound represented by the formula (IV) into 2-methoxyethanol, adding phosphoric acid and carrying out acid hydrolysis to obtain a compound represented by a formula (III), (c) hydrolyzing the compound represented by the formula (III) with sodium hydroxide, extracting with dichloromethane and adding acetic acid to neutralize to obtain a compound represented by a formula (II) and (d) in the presence of an organic alcohol solvent, adding a sodium hydroxide solution, hydrolyzing the compound represented by the formula (II) to form a salt, adding the organic alcohol solvent, cooling and crystallizing to obtain bromfenac sodium. According to the preparation method disclosed by the invention, the reaction yield of the intermediate (IV) and the quality of the product are improved, high-purity bromfenac sodium can be obtained just by virtue of crystallizing with the organic alcohol solvent, the good environmental benefit is achieved and the generation of bromfenac sodium polymer impurity is reduced.