83799-24-0

Basic information

• Product Name: Fexofenadine
• Synonyms: TERFENADINECARBOXYLATE;alpha-dimethyl-tyl)-alph;benzeneaceticacid,4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)bu;mdl16455;terfenadineacidmetabolite;2-(4-(1-HYDROXY-4-[4-(HYDROXY-DIPHENYL-METHYL)-PIPERIDIN-1-YL]-BUTYL)-PHENYL)-2-METHYL-PROPIONIC ACID;CARBOXYTERFENADINE;FEXOFENADINE
• CAS NO: 83799-24-0
• Molecular Formula: C₃₂H₃₉NO₄
• Molecular Weight: 501.66
• EINECS: 1533716-785-6
• Product Categories: Active Pharmaceutical Ingredients;Intermediates & Fine Chemicals;Metabolites;Pharmaceuticals;Histamine receptor;Aromatics;Heterocycles;Metabolites & Impurities;API
• Mol File: 83799-24-0.mol

Chemical Properties

• Melting Point: 218-220°C
• Boiling Point: 697.3 °C at 760 mmHg
• Flash Point: 375.5 °C
• Appearance: white powder
• Density: 1.171 g/cm³
• Vapor Pressure: 2.08E-20mmHg at 25°C
• Refractive Index: 1.596
• Storage Temp.: -20°C Freezer
• Solubility: Methanol (Slightly, Heated, Sonicated)
• PKA: 4.43±0.10(Predicted)
• CAS DataBase Reference: Fexofenadine(CAS DataBase Reference)
• NIST Chemistry Reference: Fexofenadine(83799-24-0)
• EPA Substance Registry System: Fexofenadine(83799-24-0)

Safety Data

• Hazardous Substances Data: 83799-24-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Fexofenadine is used as an antihistamine for the treatment of allergy symptoms such as itching, runny nose, sneezing, and watery eyes caused by histamine release. It works by blocking the action of histamine, a compound released by the body during an allergic reaction.
Used in Medical Treatments:
Fexofenadine is used as a medication for the relief of seasonal allergic rhinitis (hay fever) and chronic idiopathic urticaria (hives). It is effective in reducing the frequency and severity of these conditions, providing relief to patients suffering from allergies.
Used in Drug Formulations:
Fexofenadine is used in various drug formulations, such as tablets and oral solutions, to ensure ease of administration and optimal bioavailability. These formulations facilitate the delivery of the medication to the target site, ensuring effective treatment of allergic symptoms.

Therapeutic Function

Antihistaminic

InChI:InChI=1/C32H39NO4/c1-31(2,30(35)36)25-17-15-24(16-18-25)29(34)14-9-21-33-22-19-28(20-23-33)32(37,26-10-5-3-6-11-26)27-12-7-4-8-13-27/h3-8,10-13,15-18,28-29,34,37H,9,14,19-23H2,1-2H3,(H,35,36)

Upstream product

• 154825-96-4 fexofenadine methyl ester 
• 32454-35-6 2-(4-bromophenyl)-2-methylpropionic acid 
• 105955-84-8 4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyraldehyde 
• 50679-08-8 terfenadine 
• 76811-98-8 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetic acid 
• 826-55-1 2-methyl-2-phenylpropionic acid 
• 18755-52-7 (2-acetoxy-1,1-dimethylethyl)benzene 
• 57625-74-8 methyl 2-methyl-2-phenylpropionate 
• 252022-32-5 Methyl 2-[4-(1-hydroxy-4-chlorobutyl)phenyl]isobutyrate 
• 154477-54-0 2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid, methyl ester 
• 169032-11-5 2-(4-(4-Chloro-1-oxo-butyl))-phenyl-2-methyl propanyl acetate 
• 169032-13-7 2-[4-(1-Ethylendioxo-4-chlorobutyl)phenyl]isobutanol 
• 1126-09-6 4-carbethoxypiperidine 
• 96067-93-5 benzyl 4-(hydroxydiphenylmethyl)-piperidine-1-carboxylate 

Downstream Products

• 1133879-72-7 4-(4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)-1-hydroxybutyl)-α,α-dimethylphenylacetic acid, salt with formic acid 
• 138452-21-8 fexofenadine hydrochloride 

Relevant articles and documents

Preparation method of fexofenadine

The invention provides a preparation method of fexofenadine, which comprises the following steps: by using bromobenzene as a raw material, carrying out Friedel-Crafts acylation reaction to obtain 4'-bromo-4-chlorophenone ; enabling 4'-bromo-4-chlorobutanone and 1-methoxy-1-(trimethylsiloxy)-2-methyl-1-propene to subjected to coupling reaction to obtain 2-[4-(4 -chloro-1-butyryl)phenyl]-2-methyl methyl propionate; and sequentially carrying out N-alkylation, carbonyl reduction and alkaline hydrolysis on 2-[4-(4 -chloro-1-butyryl)phenyl]-2-methylpropanoate to obtain fexofenadine. The method has the advantages of cheap and easily available raw materials, easiness in operation, high yield, low cost, no meta-isomer, suitability for industrial production and the like.

A fexofenadine and method for synthesizing intermediate

The invention relates to a simple and efficient synthetic method of fexofenadine (chemical name: 4-{1-hydroxyl-4-[4-(hydroxyl benzhydryl)-1-piperidyl]-butyl}-alpha, alpha-dimethyl-phenylacetic acid (I)) and its intermediate. According to the method, isopropyl benzene is used as a raw material. Through a Friedel-Crafts acylation reaction, a halogenation reaction and a carbonyl insertion reaction, a key intermediate 4-(4-chloro-1-butyryl)-alpha, alpha-dimethyl phenylacetic acid (IV) is obtained; the key intermediate reacts with another raw material dibenzyl-(4-pyridyl)-methanol (E) to obtain a key pyridinium intermediate 4-{4-chloro-[4-hydroxydiphenylmethyl]-1-pyridinium]-1-butyryl}-alpha, alpha-dimethyl phenylacetic acid (V); and through catalytic hydrogenation and metallic hydrogen reduction, high-purity fexofenadine is obtained. The synthetic method provided by the invention has advantages of smooth process, simple reaction, short route, convenient post-treatment, high yield and low cost, and is a very ideal preparation method of fexofenadine and industrialization feasible route.

A fexofenadine hydrochloride process for synthesizing

The invention discloses a synthetic process of fexofenadine hydrochloride. The synthetic process of fexofenadine hydrochloride comprises the following steps of: with alpha, alpha-dimethyl phenylacetic acid as a raw material, carrying out an esterification reaction on alpha, alpha-dimethyl phenylacetic acid and absolute ethyl alcohol under the catalysis of a silica gel loaded phosphotungstic acid (PW12/SiO2) solid acid catalyst to obtain alpha, alpha-dimethyl ethyl phenylacetate; carrying out Friedel-Grafts reaction on alpha, alpha-dimethyl ethyl phenylacetate and 4-chlorobutyryl chloride to obtain alpha, alpha-dimethyl-4-(4-chloro-1-oxo butyl) ethyl phenylacetate; reducing by virtue of sodium borohydride in 95% ethyl alcohol to obtain alpha, alpha-dimethyl-4-(4-chloro-1-hydroxyl butyl) ethyl phenylacetate; and carrying out N-alkylation reaction on alpha, alpha-dimethyl-4-(4-chloro-1-hydroxyl butyl) ethyl phenylacetate and alpha, alpha-dimethyl-4-piperidine methyl alcohol in DMF (dimethyl formamide) for 24 hours at the temperature of 80 DEG C to obtain alpha, alpha-dimethyl-4-[1-hydroxyl-4-[4-(hydroxyl diphenylmethyl)-1-piperidyl]-butyl] ethyl phenylacetate, and then carrying out alkali hydrolysis and salification by virtue of hydrochloric acid, so that fexofenadine hydrochloride is obtained. The synthetic process of fexofenadine hydrochloride is high in yield and low in cost, produces less pollution and is applicable to industrial mass production.

METHODS AND COMPOSITIONS FOR TREATING INFECTION

Provided herein are compositions and methods for treating or preventing infection.

Repurposing the antihistamine terfenadine for antimicrobial activity against staphylococcus aureus

Staphylococcus aureus is a rapidly growing health threat in the U.S., with resistance to several commonly prescribed treatments. A high-throughput screen identified the antihistamine terfenadine to possess, previously unreported, antimicrobial activity against S. aureus and other Gram-positive bacteria. In an effort to repurpose this drug, structure-activity relationship studies yielded 84 terfenadine-based analogues with several modifications providing increased activity versus S. aureus and other bacterial pathogens, including Mycobacterium tuberculosis. Mechanism of action studies revealed these compounds to exert their antibacterial effects, at least in part, through inhibition of the bacterial type II topoisomerases. This scaffold suffers from hERG liabilities which were not remedied through this round of optimization; however, given the overall improvement in activity of the set, terfenadine-based analogues provide a novel structural class of antimicrobial compounds with potential for further characterization as part of the continuing process to meet the current need for new antibiotics.

INTERMEDIATES USEFUL FOR THE SYNTHESIS OF FEXOFENADINE, PROCESSES FOR THEIR PREPARATION AND FOR THE PREPARATION OF FEXOFENADINE

Intermediates useful for the synthesis of fexofenadine, processes for their preparation and processes for the synthesis of fexofenadine are described.

The synthesis of fexofenadine

This work proposes a new simple route for fexofenadine synthesis with low cost and easily obtainable raw materials. We use benzene and methallyl as starting reactants, applying steps of Friedel-Crafts alkylation reaction, hydrolysis, oxidation, esterification reaction, and reduction reaction to obtain the intermediate product, followed by N-alkylation reaction to obtain 4-{1-hydroxy-4-[4-(hydroxydiphenyl)-piperidine]butyl}-α, α-dimethylbenzene acetate. Then, the final product fexofenadine is obtained upon hydrolysis. In the synthesis process, we constantly optimize the reaction conditions such as reaction time, reaction temperature, solvent selection, and other factors, thus improving the final yield of the target product fexofenadine to 33.51 %.

PREPARATION OF 2-(4-BROMOPHENYL)-2-METHYLPROPANOIC ACID

Selective bromination of 2-methyl-2-phenylpropanoic acid in aqueous medium is described to obtain pure 2-(4-bromophenyl)-2-methylpropanoic acid, which is a useful key intermediate in the process of manufacturing pure fexofenadine.

Preparation of 2-(4-bromophenyl)-2-methylpropanoic acid

Selective bromination of 2-methyl-2-phenytpropanoic acid on aqueous medium is described to obtain pure 2-(4-bromophenyl)-2-methylpropanoic acid, which is a useful key intermediate in the process of manufacturing pure fexofenadine.

POLYMORPHIC FORM OF FEXOFENADINE HYDROCHLORIDE, INTERMEDIATES AND PROCESS FOR ITS PREPARATION

The present invention relates to a novel polymorphic form of Fexofenadine hydrochloride, to a process for preparing it, to pharmaceutical compositions containing it, as well as its use. The invention also relates to intermediates useful for the preparation of Fexofenadine hydrochloride, antihistamine drug used in the treatment of allergy symptoms.