- 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.
- -
-
Paragraph 0084-0085
(2021/04/17)
-
- 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.
- -
-
Paragraph 0047; 0053; 0064; 0065
(2018/04/26)
-
- 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.
- -
-
Paragraph 0242
(2015/09/28)
-
- 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.
- Perlmutter, Jessamyn I.,Forbes, Lauren T.,Krysan, Damian J.,Ebsworth-Mojica, Katherine,Colquhoun, Jennifer M.,Wang, Jenna L.,Dunman, Paul M.,Flaherty, Daniel P.
-
p. 8540 - 8562
(2014/12/11)
-
- 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 %.
- Ronggeng, Wang,Yougui, Zhao,Guanchao, Zhang
-
p. 2149 - 2155
(2013/06/05)
-
- 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.
- -
-
Paragraph 0107; 0108
(2013/09/26)
-
- 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.
- -
-
-
- Novel and efficient method for the synthesis of racemic fexofenadine
-
Fexofenadine is a selective H1-histamine receptor antagonist, which is an attractive alternative treatment for allergy symptoms. An efficient and environmentally friendly synthetic approach for the preparation of fexofenadine was developed from commercially available cumene. The method involves the Friedel-Craft's reaction, substitution, reduction, bromination, and the Grignard reaction. Copyright
- Raghavendra,Harsha,Vinaya,Mantelingu,Rangappa
-
p. 2296 - 2303
(2011/07/30)
-
- Process for preparing fexofenadine
-
A process for preparing fexofenadine is described, which provides for the hydrolysis of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-oxobutyl]-α,α-dimethylbenzeneacetic acid-alkyl ester, in a mixture of water and optionally an organic solvent, in the presence of a base; the carboxylate salt of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-oxobutyl]-α,α-dimethylbenzeneacetic acid is thus obtained, which is then directly reduced as carboxylate in a basic environment with hydrogen in the presence of a suitable hydrogenation catalyst to give the carboxylate of fexofenadine, which is precipitated by neutralisation of the solution.
- -
-
Page/Page column 2
(2011/08/08)
-
- Process for Preparing Fexofenadine
-
A process for preparing fexofenadine is described that includes the purification of 4-[4-chloro-1-oxobutyl]-2,2-dimethylphenyl acetic acid alkyl ester by means of suspension in a hydrocarbon, preferably n-heptane. The compound thus obtained is dissolved in a suitable solvent and condensed with azacyclanol to give the compound shown below where R is an alkyl radical, which is then hydrolysed and reduced to give fexofenadine.
- -
-
Page/Page column 2
(2010/02/17)
-
- Biooxidation of methyl group: Part 2. Evidences for the involvement of cytochromes P450 in microbial multistep oxidation of terfenadine
-
The actinomycete Streptomyces platensis grown in culture medium containing soybean peptones can transform terfenadine, an antihistamine drug, into its active metabolite fexofenadine. The microbial oxidation of methyl group of terfenadine into carboxylic acid could be an alternative to chemical ways to produce fexofenadine. This bioconversion requires three oxidation steps: a hydroxylation of one methyl group followed by the oxidation of the corresponding alcohol into the aldehyde and finally its oxidation into the carboxylic acid. The oxidation reaction of each step has been studied. Terfenadine and intermediates incubated with whole cells were not oxidized under argon whereas their biotransformation under 18O2-enriched atmosphere gave labeled fexofenadine. P450 inhibitors, such as clotrimazole or fluconazole, inhibited oxidation activity of each step. While the two last steps could be catalyzed by dehydrogenases or oxidases, this study strongly demonstrates the role of at least one, or possibly several cytochromes P450, in the oxidation of terfenadine into fexofenadine by S. platensis cells. To our knowledge, this is one of the few examples of involvement of P450s in such three steps oxidation of a xenobiotic.
- El Ouarradi, Amane,Lombard, Murielle,Buisson, Didier
-
experimental part
p. 172 - 178
(2011/02/23)
-
- ANTIHISTAMINIC PIPERIDINE DERIVATIVES AND INTERMEDIATES FOR THE PREPARATION THEREOF
-
This invention relates to novel piperidine derivatives of formula (I) and a process for the preparation thereof, wherein R1 is H or C1-C6alkyl wherein the C1-C6alkyl moiety is straight or branched; R2 is -COOH or -COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; or stereoisomers or pharmaceutically acceptable acid addition salt thereof.
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-
Page/Page column 30
(2010/11/03)
-
- PROCESS FOR PREPARING FEXOFENADINE
-
A process for preparing fexofenadine is described, which provides for the hydrolysis of 4-[4-[4-(hydroxydiphenylmethyl)-l-piperidyl]-l-oxobutyl]-α,α- dimethylbenzeneacetic acid-alkyl ester, in a mixture of water and optionally an organic solvent, in the presence of a base; the carboxylate salt of 4- [4- [4- (hydroxydiphenylmethyl)- 1 -piperidyl] - 1 -oxobutyl] -α,α -dimethylbenzeneacetic acid is thus obtained, which is directly reduced as carboxylate in a basic environment with hydrogen in the presence of a suitable hydrogenation catalyst to give the carboxylate of fexofenadine, which is precipitated by neutralisation of the solution.
- -
-
Page/Page column 5-6
(2008/06/13)
-
- PROCESS FOR PREPARING FEXOFENADINE
-
A process for preparing fexofenadine is described, comprising the purification of 4-[4-chloro-l-oxobutyl]-2,2-dimethylphenyl acetic acid alkyl ester by means of suspension in a hydrocarbon, preferably n-heptane. The compound thus obtained is dissolved in a suitable solvent and condensed with azacyclanol to give the compound shown below (I) where R is an alkyl radical, which is then hydrolysed and reduced to give fexofenadine.
- -
-
Page/Page column 5
(2008/06/13)
-
- Biooxidation of methyl group: application to the preparation of alcohol and acid metabolites of terfenadine, ebastine and analogues
-
The aim of this study was to found the best conditions to prepare metabolites of terfenadine, ebastine and analogues. For that purpose we investigated the structural substrate requirements needed for the oxidative whole cell activity and selected the most efficient conditions to obtain each compound. Our results showed that either alcohol or acid derivative arising from the oxidation of a methyl group is the main product, ratio depending on the microorganism used and on the culture conditions of cells. The oxidized metabolites were synthesized at preparative scale and isolated in 35-88% yield before characterization.
- El Ouarradi, Amane,Salard-Arnaud, Isabelle,Buisson, Didier
-
experimental part
p. 11738 - 11744
(2009/04/11)
-
- INDUSTRIAL PROCESS OF FEXOFENADINE HYDROCHLORIDE WITH CONTROLLED SIDE PRODUCTS
-
The present invention relates to a process for the preparation of Anhydrous Fexofenadine Hydrochloride with controlled level of side products. Another aspect of the present invention is purification of Fexofenadine base free of meta isomer of fexofenadine base and fexofenadinone.
- -
-
Page/Page column 8-9; 12-13
(2008/06/13)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF HIGHLY PURE FEXOFENADINE
-
The present invention provides an improved process for the preparation of highly pure 4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α,α-dimethylbenzene acetic acid (fexofenadine) of Formula (I), or its salts thereof.
- -
-
Page/Page column 7-8
(2008/06/13)
-
- INTERMEDIATES USEFUL FOR THE PREPARATION OF ANTIHISTAMINIC PIPERIDINE DERIVATIVE
-
The present invention relates to process for preparing antihistaminic piperidine derivative, specifically fexofenadine and its pharmaceutically acceptable salts by using novel synthetic intermediates of following formula (I), wherein R is lower alkyl; R2 is H, cyclopropyl, R1is alkyl, 4-(hydroxy-dipheτiyl-methyl)-piperidin-l-yl.
- -
-
Page/Page column 15
(2008/06/13)
-
- Fexofenadine base polymorphic forms
-
The invention relates to novel crystalline forms of fexofenadine base, a process for the preparation thereof and the use thereof in therapy.
- -
-
Page/Page column 3
(2008/06/13)
-
- Fexofenadine base polymorphic forms
-
The invention relates to novel crystalline forms of fexofenadine base, a process for the preparation thereof and the use thereof in therapy.
- -
-
Page/Page column 4
(2008/06/13)
-
- FEXOFENADINE CRYSTAL FORM AND PROCESSES FOR ITS PREPARATION THEREOF
-
Provided is a crystalline form of fexofenadine free base and processes for its preparation.
- -
-
Page/Page column 10
(2008/06/13)
-
- Process for production of piperidine derivatives
-
Processes are disclosed for preparing piperidine derivative compounds of the formulae I, II or III: The processes involve reacting a compound of formula Ia, IIa or IIIa with isobutyrate or an isobutyrate equivalent.
- -
-
Page/Page column 8-14
(2008/06/13)
-
- Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with an antihistamine for treatment of asthma or chronic obstructive pulmonary disease
-
A pharmaceutical or veterinary composition, comprises a first active agent selected from a dehydroepiandrosterone and/or dehydroepiandrosterone-sulfate, or a salt thereof, and a second active agent comprising an antihistamine for the treatment of asthma, chronic obstructive pulmonary disease, or any other respiratory disease. The composition is provided in various formulations and in the form of a kit. The products of this patent are applied to the prophylaxis and treatment of asthma, chronic obstructive pulmonary disease, or any other respiratory disease.
- -
-
-
- Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with an antihistamine for treatment of asthma or chronic obstructive pulmonary disease
-
A pharmaceutical or veterinary composition, comprises a first active agent selected from a dehydroepiandrosterone and/or dehydroepiandrosterone-sulfate, or a salt thereof, and a second active agent comprising an antihistamine for the treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases. The composition is provided in various formulations and in the form of a kit. The products of this patent are applied to the prophylaxis and treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases.
- -
-
-
- Microbial oxidation of terfenadine and ebastine into fexofenadine and carebastine
-
Fexofenadine 5 and carebastine 6 were obtained in good yield by optimization of culture conditions of microorganisms. Oxidation of 1 into 9 was observed as described in mammalian metabolism. The oxidation of tert-butyl-phenyl group of title compounds by s
- Mazier, Claire,Jaouen, Maryse,Sari, Marie-Agnès,Buisson, Didier
-
p. 5423 - 5426
(2007/10/03)
-
- Process and diastereomeric salts useful for the optical resolution of racemic a-[4- (1,1-dimethylethy) phenyl) -4- (hydroxydipenylmethyl) -1-piperidinebutanol and derivative compounds
-
A process and diastereomeric salts useful for the optical resolution of racemic alpha-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol, 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic acid and lower alkyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetates. The process comprises placing into solution a chiral resolving agent, either (+)/(-)-di-paratoluoyltartaric acid or (-)/(+)-mandelic acid, in an amount equimolar to a compound corresponding to the desired enantiomer of the above compound, precipitating the resulting diastereomeric salt between the chiral resolving agent and the target enantiomer and separating the enantiomer.
- -
-
-
- Processes for the production of fexofenadine
-
An improved process for the manufacture of fexofenadine is described in which a compound of formula (F): wherein R2 represents COOH, COO—C1-6 alkyl or CN; and R3 represents hydrogen, mesylate, triflate, tosylate or carboxy-C1-6-alkyl, or a salt thereof is prepared by: (I) reacting a compound of formula (B): wherein R1 represents hydrogen or carboxy-C1-6-alkyl; and R2 is a hereinbefore defined, with a copper and/or silver compound in the presence of palladium or a compound thereof to yield a compound of formula (C): wherein R1, and R2 are as hereinbefore defined; (II) converting said compound of formula (C) into a compound of formula (E): wherein R2 and R3 are as hereinbefore defined and R4 represents a halogen atom, and (III) reacting said compound of formula (E) with azacyclonol.
- -
-
-
- Process for the production of piperidine derivatives with microorganisms
-
The present invention relates to the production of a product compound having a structure according to Formulae IA and/or IB: wherein n is 0 or 1; R1is hydrogen or hydroxy; R2is hydrogen; or, when n is 0, R1and R2taken together form a second bond between the carbon atoms bearing R1and R2, provided that when n is 1, R1and R2are each hydrogen; R3is —COOH or —COOR4; R4is an alkyl or aryl moiety; A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, and alkoxy. This process involves incubating a starting compound having a structure according to Formulae IIA and/or IIB: wherein R3is —CH3and R1, R2, A, B, and D are defined above In the presence of a microorganism under conditions effective to produce the product compound. The microorganism can be from the genus Streptomyces, Stemphylium, Gliocladium, Bacillus, Botrytis, Cyathus, Rhizopus, Pycniodosphora, Psuedomonas, Helicostylum, Aspergillus, Mucor, Gelasinospora, Rhodotorula, Candida, Mycobacterium, or Pennicillium. Alternatively, the microorganism can beCunninghamella bainieri.
- -
-
-
- Intermediates useful for the preparation of antihistaminic piperidine derivatives
-
The present invention is related to a novel intermediates and processes which are useful in the preparation of certain antihistaminic piperidine derivatives of the formula whereinW represents —C(=O)— or —CH(OH)—;R1 represents hydrogen or hydroxy;R2 represents hydrogen;R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2;n is an integer of from 1 to 5;m is an integer 0 or 1;R3 is —COOH or —COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched each of A is hydrogen or hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof,with the proviso that where R1 and R2 are taken together to form a second bond between the carbon atoms bearing R1 and R2 or where R1 represented hydroxy, m is an integer 0.
- -
-
Page column 108
(2010/01/30)
-
- Process for the preparation of 4-[1-hydroxy-4-[4-(hydroxydiphenylmethly)-1-piperidinyl]-butyl]-alpha,alpha-dimethylbenzeneacetic acid
-
A process for the preparation of 4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α,α-dimethylbenzeneacetic acid (Fexofenadine) of formula 1
- -
-
-
- Process for the production of piperidine derivatives with microorganisms
-
The present invention relates to the production of a product compound having a structure according to Formulae IA and/or IB: wherein n is 0 or 1; R1 is hydrogen or hydroxy; R2 is hydrogen; or, when n is 0, R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2, provided that when n is 1, R1 and R2 are each hydrogen; R3 is —COOH or —COOR4; R4 is an alkyl or aryl moiety; A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, and alkoxy. This process involves incubating a starting compound having a structure according to Formulae IIA and/or IIB: wherein R3 is —CH3 and R1, R2, A, B, and D are defined above. in the presence of a microorganism under conditions effective to produce the product compound. The microorganism can be from the genus Streptomyces, Stemphylium, Gliocladium, Bacillus, Botrytis, Cyathus, Rhizopus, Pycniodosphora, Psuedomonas, Helicostylum, Aspergillus, Mucor, Gelasinospora, Rhodotorula, Candida, Mycobacterium, or Pennicillium. Alternatively, the microorganism can be Cunninghamella bainieri.
- -
-
-
- Antihistaminic piperidine derivatives and intermediates for the preparation thereof
-
This invention relates to novel piperidine derivatives of formula (I) and a process for the preparation thereof.whereinR1 is H or C1-C6alkyl wherein the C1-C6alkyl moiety is straight or branched;R2 is -COOH or -COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; orstereoisomers or pharmaceutically acceptable acid addition salt thereof.
- -
-
Page column 25
(2010/02/05)
-
- Process for production of piperidine derivatives
-
The present invention relates to a method for preparing piperidine derivative compounds by converting, with a piperidine compound, regioisomers having the formula: and where m is an integer from 1 to 6; Q and Y are the same or different and are selected from the group consisting of O, S, and NR5; G1, G2, and G3 are the same or different and are selected from the group consisting of OR8, SR8, and NR8R9; R6 and R7 are the same or different and are selected from the group consisting of hydrogen, an alkyl moiety, an aryl moiety, OR8, SR8, and NR8R9; X3 is halogen, OR15, SR15, NR15R16, OSO2R15, or NHSO2R15; R5, R8, R9, R15, and R16 are the same or different and are selected from the group consisting of hydrogen, an alkyl moiety, and an aryl moiety; and A is a substituent of its ring and is selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, alkoxy, and other substituents.
- -
-
-
- Intermediates useful for the preparation of antihistaminic piperidine derivatives
-
The present invention is related to a novel intermediates and processes which are useful in the preparation of certain antihistaminic piperidine derivatives of the formula wherein W represents —C(═O)— or —CH(OH)—; R1represents hydrogen or hydroxy; R2represents hydrogen; R1and R2taken together form a second bond between the carbon atoms bearing R1and R2; n is an integer of from 1 to 5; m is an integer 0 or 1; R3is —COOH or —COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; each of A is hydrogen or hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R1and R2are taken together to form a second bond between the carbon atoms bearing R1and R2or where R1represented hydroxy, m is an integer 0.
- -
-
-
- Intermediates useful for the preparation of antihistaminic piperidine derivatives
-
The present invention is related to a novel intermediates and processes which are useful in the preparation of certain antihistaminic piperidine derivatives of the formula wherein W represents -C(=O)- or -CH(OH)-; R1 represents hydrogen or hydroxy; R2 represents hydrogen; R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2; n is an integer of from 1 to 5; m is an integer 0 or 1; R3 is -COOH or -COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched each of A is hydrogen or hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R1 and R2 are ta to form a second bond between the carbon R1 and R2 or where R1 represented hydroxy integer 0.
- -
-
-
- Process for production of piperidine derivatives
-
The present invention relates to a method for preparing piperidine derivative compounds by converting, with a piperidine compound, regioisomers having the formula: where Z is -CG1G2G3, and where m is an integer from 1 to 6; Q and Y are the same or different and are selected from the group consisting of O, S, and NR5; G1, G2, and G3 are the same or different and are selected from the group consisting of OR8, SR8, and NR8R9; and R5, R8, and R9 are the same or different and are selected from the group consisting of hydrogen, an alkyl moiety, and an aryl moiety.
- -
-
-
- A new synthesis of carboxyterfenadine (fexofenadine) and its bioisosteric tetrazole analogs
-
A new synthesis of carboxyterfenadine (4), based on the conversion of a α-halo-alkylarylketone into the corresponding substituted 2-arylalkanoic ester, is described. The enantioselective synthesis of its two bioisosteric tetrazole analogs together with preliminary biological results are reported. Copyright (C) 1999 Elsevier Science S.A.
- Di Giacomo, Barbara,Coletta, Donato,Natalini, Benedetto,Ni, Ming-Hong,Pellicciari, Roberto
-
p. 600 - 610
(2007/10/03)
-
- Synthesis of terfenadine and derivatives
-
Processes for preparing compounds having the general formula: STR1 wherein R1a is protected carboxy, carboxy, hydroxymethyl, protected hydroxymethyl, or methyl are disclosed. Processes of the invention begin with a starting material of the general formula II STR2 and elaborate the product by reductive amination of an aldehyde of formula IVa STR3 with α,α-diphenyl-4-piperidinemethanol.
- -
-
-
- An efficient and facile synthesis of racemic and optically active fexofenadine
-
In efficient and practical method for the synthesis of racemic and optically active (96% ee) fexofenadine is described. The key racemic or optically active lactol intermediate 2 is prepared from readily available tolyl derivative 3.
- Fang, Qun K.,Senanayake, Chris H.,Wilkinson, H. Scott,Waid, Stephen A.,Li, Hui
-
p. 2701 - 2704
(2007/10/03)
-
- Synthesis of terfenadine carboxylate
-
A synthesis of terfenadine carboxylate, 1, a metabolite of terfenadine 2, is described. In the key step, the sodium salt of 2-(4-bromo-phenyl)-2-methylpropionic acid, 7, was lithiated via a metal-halogen exchange using t-BuLi and subsequently condensed with 4-[4-(hydroxydiphenylmethylpiperidin-1-yl]butyraldehyde, 5, to afford terfenadine carboxylate, 1.
- Patel, Sunil,Waykole, Liladhar,Repic, Oljan,Chen, Kau-Ming
-
p. 4699 - 4710
(2007/10/03)
-
- PIPERIDINE DERIVATIVES
-
The present invention relates to substantially pure piperidine derivative compounds of the formulae: STR1 wherein R 1 is hydrogen or hydroxy;R 2 is hydrogen;or R 1 and R 2 taken together form a second bond between the carbon atoms bearing R 1 and R 2 ;R 3 is--COOH or--COOR 4 ;R 4 has 1 to 6 carbon atoms; A, B, and D are the substituents of their respective rings each of which may be different or the same and are hydrogen, halogens, alkyl, hydroxy, alkoxy, or other substituents. A process of preparing such piperidine derivative compounds in substantially pure form is also disclosed.
- -
-
-
- PIPERIDINE DERIVATIVES
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Novel compounds of the following formula: wherein R1 is hydrogen or hydroxy; R2 is hydrogen; or R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2; n is an integer of from 1 to 5; R3 is -CH3, -CH2OH, -COOH or-COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; and each of A and B is hydrogen or hydroxy; with the provisos that at least one of A or B is hydrogen and one of A or B is other than hydrogen when R3 is -CH3; and pharmaceutically acceptable salts thereof
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