125602-71-3

Usage

Uses

Used in Pharmaceutical Industry:
Bepotastine is used as a histamine H1 receptor antagonist for the treatment of itching associated with allergic conjunctivitis. It works by selectively blocking the histamine H1 receptors, reducing the allergic inflammatory processes and providing relief from itching.
Used in Allergy Treatment:
Bepotastine is used as an anti-allergic agent for suppressing allergic inflammatory processes such as allergic rhinitis, chronic urticaria, and pruritus associated with skin conditions like eczema/dermatitis, prurigo, or pruritus cutaneus. By blocking histamine H1 receptors, it helps alleviate the symptoms of these allergic reactions.

InChI:InChI=1/C21H25ClN2O3/c22-17-8-6-16(7-9-17)21(19-4-1-2-12-23-19)27-18-10-14-24(15-11-18)13-3-5-20(25)26/h1-2,4,6-9,12,18,21H,3,5,10-11,13-15H2,(H,25,26)/t21-/m0/s1

Upstream product

• 27652-89-7 (4-chlorophenyl)-2-pyridylmethanol 
• 207726-35-0 4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine-1-carboxylic acid ethyl ester 
• 6318-51-0 2-(4-chlorobenzoyl)pyridine 
• 210095-55-9 (S)-(-)-2-((4-chlorophenyl)(piperidin-4-yloxy)methyl)pyridine 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 4045-22-1 N-acetyl-4-hydroxypiperidine 
• 1560797-69-4 (S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino] butyric acid D-menthyl ester 
• 1560797-70-7 (S)-4-{4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino}butyric acid D-menthyl ester L-tartrate 
• 1560797-65-0 (RS)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid D-menthyl ester 
• 122368-54-1 4-[(4-chlorophenyl)(pyridin-2-yl)methoxy]piperidine 
• 1563017-46-8 (4-chlorophenyl)(1-oxido-2-pyridinyl)methanone 
• 176022-47-2 (S)-(+)-(4-chlorophenyl)-(2-pyridyl)methanol 

Downstream Products

• 125602-71-3 [14C]-Bepotastine besilate 
• 210095-55-9 (S)-(-)-2-((4-chlorophenyl)(piperidin-4-yloxy)methyl)pyridine 
• 176022-47-2 (S)-(+)-(4-chlorophenyl)-(2-pyridyl)methanol 
• 1160415-45-1 (S)-4-[4-[(4-chlorophenyl)-2-pyridylmethoxy]piperidin-1-yl]butyric acid p-toluenesulfonate 

Relevant academic research and scientific papers

Identification, Characterization and HPLC Quantification of Process-Related Impurities in Bepotastine Besilate Bulk Drug

Bepotastine besilate (here after referred to as BTST), chemically known as ({d(S)4[4[(4chlorophenyl) (2pyridyl) methoxy] piperidino} butyric acid monobenzene sulphonate), is a second-generation antihistamine drug. To the best of our knowledge, no studies concerning the isolation or identification of process-related impurities have been reported so far. The current study reports the development and validation of a stability-indicating RP-HPLC method for the separation and identification of 5 potential impurities in bepotastine besilate. In this experiment, the structures of 3 process-related impurities were found to be new compounds. They were characterized and confirmed by NMR and MS spectroscopy analyses. These 3 new compounds were proposed to be (S)-4-[(phenyl)-2-pyridinylmethoxy]-1-piperidinebutanoic acid,(Imp-A); 4-[(S)-(4-chlorophenyl)-2-pyridinylmethoxy]-1- piperidinebutyric acid, N-oxide (Imp-B) and (S)-4-[(4- chlorophenyl)-2-pyridinylmethoxy]-1-piperidylethane (Imp-C). In addition, an efficient optimized chromatographic method was performed on a Shimadzu Inertsil C8-3 column (150 mm×4.6 mm, 3 μm) to separate and quantify these 5 impurities. It was using 15 mmol ammonium formate buffer in water (pH adjusted to 3.8 with formic acid) and acetonitrile as the mobile phase in gradient mode. The method was developed to separate and quantify these 5 impurities obtained in the range of 0.05-0.75 μg/mL. It was validated and proven to be selective, accurate and precise and suitable. It is the first publication of identification and characterization data of the 3 new compounds. It is also the first effective HPLC method for separation and quantification of all of process-related impurities in bepotastine besilate.

Total synthesis method of bestatin

The method comprises the following steps: (4 - chlorophenyl) (2 - pyridyl) - methanol as a starting raw material, and sequential addition reaction. Examples of the etherification reaction include a deprotection reaction, a chiral resolution, a condensation reaction, a hydrolysis reaction, and the like. The synthesis method has the advantages of cheap and easily available raw materials, no need of expensive chiral catalysts, simpler synthesis method, mild conditions, less side reactions and low cost.

METHOD FOR MAKING PIPERIDINE DERIVATIVE INTO RACEMATE

PROBLEM TO BE SOLVED: To provide a method for making efficiently a (R)-piperidine derivative into a racemate, and a method for producing a (S)-piperidine derivative from the racemate. SOLUTION: A method for producing a piperidine derivative of a racemate

IMPROVED PROCESS FOR THE MANUFACTURE OF BEPOTASTINE AND ITS BESILATE SALT

The present invention discloses a process for preparation of Bepotastine and its Besilate salt of formula I with good yield and purity. The invention also describes a process for recycle and reuse of the Ethyl-4-hydroxy piperidine-1-carboxylate from the aqueous medium after isolating the 2-[(S)-(4-Chlorophenyl)(piperidin-4- yloxy)methyl]pyridine, for subsequent batches in the production of Ethyl 4-[(4- Chlorophenyl)(pyridin-2-yl)methoxy]piperidine-1-carboxylate. The invention further discloses novel intermediates, viz., 2-[Chloro(4- chlorophenyl)methyl]pyridine hydrochloride and bis{2-[(S)-(4- Chlorophenyl)(piperidin-4-yloxy)methyl]pyridine} Dibenzoyl tartrate, useful in the preparation of Bepotastine and its Besilate salt.

Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl N-Heteroaryl Ketones with N-Oxide as a Removable ortho-Substituent

A highly enantioselective transfer hydrogenation of non-ortho-substituted aryl N-heteroaryl ketones, using readily available chiral diamine-derived iridium complex (S,S)-1f as a catalyst and sodium formate as a hydrogen source in a mixture of H2O/i-PrOH (v/v = 1:1) under ambient conditions, is described. The chiral aryl N-heteroaryl methanols were obtained with up to 98.2% ee by introducing an N-oxide as a removable ortho-substituent. In contrast, no more than 15.1% ee was observed in the absence of an N-oxide moiety. Furthermore, the practical utility of this protocol was also demonstrated by gram-scale asymmetric synthesis of bepotastine besilate in 51% total yield and 99.9% ee.

A stable besylate bepotastine crystal and its preparation method

The invention discloses a stable bepotastine besilate crystal in novel crystal form through a recrystallization method. The obtained bepotastine besilate crystal is confirmed through X-ray powder diffraction and infrared spectrum. Stability contrast experiments prove that the provided bepotastine besilate crystal has extremely high stability, and both bulk drug and preparation of the bepotastine besilate crystal have stability obviously better than that of existing bepotastine besilate crystals.

Asymmetric syntheses method of ophthalmologic drug bepotastine besilate

The invention relates to an asymmetric synthesis method of an ophthalmologic drug pylistramine besylate. The method concretely comprises the following steps: oxidizing (4-chlorophenyl)(2-pyridyl)methanone to obtain (4-chlorophenyl)(2-pyridyl)ketone-N-oxide; carrying out asymmetric transfer hydrogenation reduction on the (4-chlorophenyl)(2-pyridyl)ketone-N-oxide through using a complex of monosulfonyl chiral diamine and metallic ruthenium, rhodium and iridium as a catalyst and a sodium formate or formic acid and triethylamine mixture or isopropanol as a hydrogen source in order to prepare (S)-(4-chlorophenyl)(2-pyridyl)methanol-N-oxide; reducing the (S)-(4-chlorophenyl)(2-pyridyl)methanol-N-oxide to prepare (S)-(4-chlorophenyl)(2-pyridyl)methanol; and condensing the (S)-(4-chlorophenyl)(2-pyridyl)methanol and ethyl 4-(4-bromopiperidine-1-yl)butyrate to obtain the ophthalmologic drug pylistramine besylate. The total yield is 61.6%.

Novel chiral resolving agent and Method for optically resolving preparation of (RS)-Bepotastine using thereof

The present invention relates to a method for optically resolving (RS)-bepotastine by directly optically resolving (RS)-bepotastine by using an optical resolution agent. Different to a conventional method of optically resolving (RS)-bepotastine by attaching a subsidiary group having optical activity to the end of the (RS)-bepotastine, the method for optically resolving (RS)-bepotastine according to the present invention is a novel preparation method for directly optically resolving (RS)-bepotastine by using an optical resolution agent only. The method of the present invention optically resolves (RS)-bepotastine into (S)-bepotastine with high yield and high optical purity.

Preparation method of anti-allergic drug bepotastine

The invention discloses a preparation method of an anti-allergic drug bepotastine, and relates to the technical field of anti-allergic drugs. The technical point of the invention is that a compound (S)-(4-chlorophenyl)(2-pyridyl)-methanol (formula II) is adopted as an initial raw material and is subjected to a reaction with N-tert-butoxycarbonyl-4-halopiperidine, such that a compound (S)-N-tert-butoxycarbonyl-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine (formula III) is obtained; under an acidic condition, the protecting group of the compound represented by the formula (III) is removed, such that a compound (S)-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine (formula IV) is obtained; the compound represented by the formula (IV) is subjected to a nucleophilic substitution reaction with 4-chlorobutanamide, such that a compound (S)-4-[(4-chlorophenyl)(2-pyridyl)methoxy]-piperidinyl]-butyramide (formula V) is obtained; the amide group of the compound represented by the formula (V) is hydrolyzed, such that the target product which is the anti-allergic drug bepotastine is obtained. The method provided by the invention has the advantages of simple synthesis route and low cost, and is suitable for large-scale production of the optically pure anti-allergic drug bepotastine.