86347-14-0

Basic information

• Product Name: Medetomidine
• Synonyms: Medetomidine;4-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazole;( -)-4-(alpha,2,3-Trimethylbenzyl)imidazole;(Rs)-4-(alpha,2,3-trimethylbenzyl)imidazol;1H-Imidazole, 4-(1-(2,3-dimethylphenyl)ethyl)-;86347-15-1 (Hydrochloride);Medetomidina;Medetomidina [spanish]
• CAS NO: 86347-14-0
• Molecular Formula: C₁₃H₁₆N₂
• Molecular Weight: 200.2795
• EINECS: 1592732-453-0
• Mol File: 86347-14-0.mol

Chemical Properties

• Boiling Point: 381.9 °C at 760 mmHg
• Flash Point: 191.3 °C
• Appearance: /
• Density: 1.053
• Vapor Pressure: 1.08E-05mmHg at 25°C
• Refractive Index: 1.569
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Soluble in DMSO
• PKA: 14.29±0.10(Predicted)
• CAS DataBase Reference: Medetomidine(CAS DataBase Reference)
• NIST Chemistry Reference: Medetomidine(86347-14-0)
• EPA Substance Registry System: Medetomidine(86347-14-0)

Safety Data

• Hazardous Substances Data: 86347-14-0(Hazardous Substances Data)

Usage

Adverse Reactions

As with all α2-agonists, the potential for isolated cases of hypersensitivity, including paradoxical response (excitation), exists. Incidents of prolonged sedation, bradycardia, cyanosis, vomiting, apnea, death from circulatory failure with severe congestion of lungs, liver, kidney and recurrence of sedation after initial recovery have been reported.

Uses

Different sources of media describe the Uses of 86347-14-0 differently. You can refer to the following data:
1. Analgesic (veterinary); sedative (veterinary).
2. Medetomidine is used in method for synthesizing Medetomidine using 2,3-Dimethylphenylmagnesium Bromide.

Indications

Medetomidine Hydrochloride is indicated for use as a sedative and analgesic in dogs over 12 weeks of age to facilitate clinical examinations, clinical procedures, minor surgical procedures not requiring muscle relaxation, and minor dental procedures where intubation is not required. The IV route of administration is more efficacious for dental care.

Clinical Use

Medetomidine is a potent non-narcotic α2-adrenoreceptor agonist which produces sedation and analgesia. These effects are dose dependent in depth and duration. Profound sedation and recumbency, with reduced sensitivity to environmental stimuli (sounds, etc.), are seen with medetomidine.

Side effects

Bradycardia with occasional atrioventricular blocks will occur together with decreased respiratory rates. Body temperature is slightly or moderately decreased. Urination typically occurs during recovery at about 90 to 120 minutes posttreatment. In approximately 10% of treated dogs, occasional episodes of vomiting occur between 5 to 15 minutes posttreatment. An increase in blood glucose concentration is seen due to α2-adrenoreceptor-mediated inhibition of insulin secretion.

Veterinary Drugs and Treatments

Medetomidine is labeled for use as a sedative and analgesic in dogs over 12 weeks of age to facilitate clinical examinations and procedures, minor surgical procedures not requiring muscle relaxation, and minor dental procedures not requiring intubation. The manufacturer recommends the IV route of administration for dental procedures. Medetomidine has also been used in cats, primarily in Europe. But there is apparently much less data available to evaluate its use; caution is advised.

Precautions

In extremely nervous or excited dogs, levels of endogenous catecholamines are high due to the animal’s state of agitation. The pharmacological response elicited by α2-agonists (e.g., medetomidine) in such animals is often reduced, with depth and duration of sedative/analgesic effects ranging from slightly diminished to nonexistent. Highly agitated dogs should therefore be put at ease and allowed to rest quietly prior to receiving Medetomidine Hydrochloride. Allowing dogs to rest quietly for 10 to 15 minutes after injection may improve the response to Medetomidine Hydrochloride. In dogs not responding satisfactorily to treatment with Medetomidine Hydrochloride, repeat dosing is not recommended.

InChI:InChI=1/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15)

Upstream product

• 176721-03-2 4-<1-(2,3-dimethylphenyl)-1-hydroxyethyl>-1-(triphenylmethyl)imidazole 
• 576-23-8 2,3-dimethylbromobenzene 
• 176721-02-1 4-<(2,3-dimethylphenyl)carbonyl>-1-(triphenylmethyl)imidazole 
• 176721-01-0 4-<(2,3-dimethylphenyl)hydroxymethyl>-1-(triphenylmethyl)imidazole 
• 60907-90-6 1-(2,3-dimethylphenyl)ethanol 
• 18156-74-6 1-(Trimethylsilyl)imidazole 
• 603-79-2 2,3-dimethylbenzoic acid 
• 21900-46-9 2,3-dimethylbenzoyl chloride 
• 1311376-16-5 (2,3-dimethylphenyl)-imidazol-1-yl-methanone 
• 1311376-17-6 3-(benzylamino)-1-(2,3-dimethylphenyl)-2-nitroprop-2-en-1-one 
• 1311376-18-7 2-amino-3-(benzylamino)-1-(2,3-dimethylphenyl)prop-2-en-1-one 
• 1311376-20-1 1-benzyl-4-(1-(2,3-dimethylphenyl)vinyl)-1H-imidazole 
• 1311376-14-3 2-nitrophenyl 2,3-dimethylbenzoate 
• 1311376-15-4 1-(2,3-dimethylphenyl)-2-nitroethanone 

Downstream Products

• 86347-15-1 (±)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole hydrochloride 
• 176721-04-3 (S)-dexmedetomidine-L-(+)-tartrate 
• 113775-47-6 dexmedetomidine 
• 145108-58-3 (-)-(R)-4-(1-[2,3-dimethylphenyl]ethyl)-1H-imidazole hydrochloride 
• 119717-21-4 (+)-(S)-4-(1-[2,3-dimethylphenyl]ethyl)-1H-imidazole 
• 145108-58-3 medetomidine hydrochloride 
• 1372802-81-7 (rac)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole oxalate 

Relevant articles and documents

Novel method for the preparation of Medetomidine

The present invention relates to a method for manufacturing medetomidine from 1H-imidazole-4-carbaldehyde and 1-bromo-2,3-dimethylbenzene. The present invention provides a novel method for manufacturing medetomidine represented by chemical formula I. The method for manufacturing medetomidine according to the present invention has an effect of having stability of a manufacturing process and being able to manufacture a final material with high purity.

Preparation method of high-purity dexmedetomidine hydrochloride

The invention discloses a preparation method of high-purity dexmedetomidine hydrochloride, which comprises the following steps: by taking 1-(1-chloroethyl)-2, 3-dimethyl benzene and N-trimethylsilylimidazole as reaction raw materials, carrying out Friedel-Crafts alkylation reaction under the catalysis of an aprotic organic solvent and lewis acid, recrystallizing the obtained post-treated oil by using a specific solvent to obtain medetomidine solid, splitting by chiral acid, free of alkali and salt forming, and preparing the high-purity dexmedetomidine hydrochloride. According to the dexmedetomidine hydrochloride prepared by the preparation method disclosed by the invention, the splitting and refining times can be effectively reduced, the chemical purity and optical purity of the obtained dexmedetomidine hydrochloride can reach 100%, and the total yield is relatively high; and moreover, main starting materials are conventional industrial commodities, so that the preparation method is suitable for industrial production and has relatively high industrial application value.

Synthetic process of dexmedetomidine hydrochloride

The present invention provides a dexmedetomidine hydrochloride synthesis process, and relates to the technical field of drug synthesis, the dexmedetomidine hydrochloride synthesis process uses 1-(1-chloroethyl)-2,3-xylene and trimethylsilylimidazole as starting materials, and alkylation, resolution, dissociation and salification reactions are performed to synthesize the dexmedetomidine hydrochloride. According to the method, L-tartaric acid is used as a resolving agent, and the resolving efficiency is improved by controlling the proportion of the resolving agent and the number of resolving times; a one-step method is adopted for free salification, intermediate quality control and purification steps are not needed, the purity of the prepared finished product is larger than 99.8%, the isomeris not larger than 0.2%, through process optimization, the efficiency of the synthesis process is remarkably improved, and the obtained finished product directly meets the commercial production requirements of raw material medicines.

Preparation method of dexmedetomidine hydrochloride

The invention discloses a preparation method of dexmedetomidine hydrochloride. The preparation method comprises the following steps: in a reaction solvent dichloromethane, carrying out a Friedel-Crafts reaction on 1-(1-chloroethyl)-2,3-dimethylbenzene and N-TMS imidazole under the action of lewis acid titanium tetrachloride to generate medetomidine; in a reaction solvent ethanol, resolving medetomidine by using L-(+)-tartaric acid to obtain medetomidine with a dextrorotation configuration; in a reaction solvent ethyl acetate, salifying dexmedetomidine in a hydrochloric acid solution to obtaina crude dexmedetomidine hydrochloride product; and finally, carrying out refining in a recrystallization mode to obtain a finished dexmedetomidine hydrochloride product. The preparation method has fewsteps, is simple and convenient to operate and is suitable for industrial production.

Method for synthesizing dexmedetomidine hydrochloride

The invention belongs to the technical field of drug preparation, and particularly relates to a method for synthesizing dexmedetomidine hydrochloride. The method for synthesizing dexmedetomidine hydrochloride comprises the steps that reaction of 2,3-dimethylbenzoyl chloride and 1-N,N-dimethyl sulfonyl-2-(tert-butyldimethylsily)-5-(2,3-dimethyl benzoyl) imidazole is adopted, reflux is carried out to remove a protecting group under the action of hydrochloric acid, intermediate 4(5)-(2,3-dimethyl benzoyl) imidazole is obtained, lastly, reduction is carried out to obtain medetomidine under the action of monomethylamine, dexmedetomidine is obtained through the resolution of medetomidine under the action of tartaric acid, and lastly, dexmedetomidine is salified with hydrochloric acid to obtain dexmedetomidine hydrochloride. Compared with the prior art, the method for synthesizing dexmedetomidine hydrochloride has the advantages that a synthetic route is shorter, the operation is easy, and astarting material is easy to obtain.

Preparation method of dexmedetomidine hydrochloride and its intermediate

The invention discloses a preparation method of dexmedetomidine hydrochloride and its intermediate. A preparation method of dexmedetomidine L-tartrate comprises the steps of subjecting dexmedetomidineintermediate III and hydrogen to reduction reaction in an organic solvent in the presence of a chiral catalyst, and subjecting the reduced product and tartaric acid to neutralization reaction to obtain dexmedetomidine L-tartrate II, wherein the chiral catalyst is (+)-1,2-bis(2S-5S)-diethylphospholano-benzene(1,5-cyclooctadiene)rhodium trifluoromethanesulfonate. The preparation method herein has ashort step path, has no need for chiral splitting, and has high total molar yield; the product prepared herein has high purity, reaches the standard for bulk pharmaceutical chemicals and is suitablefor industrial production.

Process method for preparation of dexmedetomidine hydrochloride

The invention provides a synthetic method for dexmedetomidine hydrochloride. The synthetic method is characterized in that the dexmedetomidine hydrochloride is synthesized by using 2,3-dimethyl benzaldehyde and (1-(trimethylsilyl)-1H-imidazole-4-yl)magnesium bromide as starting materials through a reaction. The method adopts Dess-Martin to synthesize a compound III, and uses a Wittig reagent to synthesize a compound IV, so reaction conditions are greatly reduced, and synthetic reaction steps are shortened. The synthetic method provided by the invention has the advantages of simple operation, mild control points, high product purity, and applicability to industrial production.

Industrial preparation method of dexmedetomidine hydrochloride

The invention discloses an industrial preparation method of dexmedetomidine hydrochloride, and belongs to the field of medicines. The method comprises the following steps: directly carrying out a Friedel-Crafts alkylation reaction on initial raw materials comprising 1-(2,3-dimethylphenyl)ethanol not subjected to a chlorination (thionyl chloride) reaction and protected imidazole under the catalysis of a Lewis acid to obtain racemic dexmedetomidine, carrying out pre-resolution purification on the racemic dexmedetomidine through a chiral acid, carrying out chiral acid resolution and alkali dissociation, and adding a hydrochloric acid organic solvent to form a salt in order to obtain the dexmedetomidine hydrochloride. The method avoids use of the toxic and corrosive regent thionyl chloride, allows the above product with high chiral and chemical purity to be obtained and the yield to be high, and is suitable for industrial production.

A novel and facile route for the synthesis of medetomidine as the α2-adrenoceptor agonist

Abstract: We report here a novel and facile method for the synthesis of (±)-4(5)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole (medetomidine) in a good yield in five steps. The method involves Wittig olefination of the phenylimidazolylketones, followed by a hydrogenation. We demonstrate that the Wittig alkenylation reaction provides a convenient step for the synthesis of medetomidine without requiring methylation and dehydration steps, which are problematic processes in the previous methods. Graphical Abstract: Novel route for the synthesis of medetomidine.[Figure not available: see fulltext.].

Selective Oxidation of Secondary Amines to N,N-Disubstituted Hydroxylamines by Choline Peroxydisulfate

N,N-Disubstituted hydroxylamines were prepared directly from secondary amines by a reliable method using an oxidizing task-specific ionic liquid, choline peroxydisulfate. The operational simplicity, high selectivity, and green reaction conditions, make this method efficient and practical.