176721-04-3

Basic information

• Product Name: (S)-dexmedetomidine-L-(+)-tartrate
• Synonyms: (S)-dexmedetomidine-L-(+)-tartrate
• CAS NO: 176721-04-3
• Molecular Weight: 350.371
• Mol File: 176721-04-3.mol

Chemical Properties

• CAS DataBase Reference: (S)-dexmedetomidine-L-(+)-tartrate(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-dexmedetomidine-L-(+)-tartrate(176721-04-3)
• EPA Substance Registry System: (S)-dexmedetomidine-L-(+)-tartrate(176721-04-3)

Safety Data

• Hazardous Substances Data: 176721-04-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-dexmedetomidine-L-(+)-tartrate is used as a sedative and analgesic agent for its ability to induce sedation and provide pain relief. It is particularly useful in medical and veterinary applications where a controlled level of sedation and analgesia is required.
Used in Anesthesia:
In the field of anesthesia, (S)-dexmedetomidine-L-(+)-tartrate is used as an adjunct to general anesthesia to provide a calm and cooperative patient, reduce the need for additional anesthetic agents, and maintain hemodynamic stability during surgery.
Used in Intensive Care Units (ICUs):
(S)-dexmedetomidine-L-(+)-tartrate is used in ICU settings to provide light to moderate sedation for patients who require mechanical ventilation or are undergoing critical care procedures.
Used in Pain Management:
(S)-dexmedetomidine-L-(+)-tartrate is also used in pain management, particularly for postoperative pain relief and in patients with chronic pain conditions, due to its analgesic properties and ability to reduce the need for opioids.
Used as an Impurity in Dexmedetomidine Production:
(S)-dexmedetomidine-L-(+)-tartrate is recognized as an impurity in the production of Dexmedetomidine, which is important for quality control and ensuring the safety and efficacy of the final product.

Upstream product

• 87-69-4 L-Tartaric acid 
• 86347-14-0 medetomidine 
• 60907-90-6 1-(2,3-dimethylphenyl)ethanol 
• 5779-93-1 2,3-dimethylbenzaldehyde 
• 176721-03-2 4-<1-(2,3-dimethylphenyl)-1-hydroxyethyl>-1-(triphenylmethyl)imidazole 
• 850716-46-0 tert-butyl 4-acetyl-1H-imidazole-1-carboxylate 
• 576-23-8 2,3-dimethylbromobenzene 
• 61985-25-9 1-(1H-imidazol-4-yl)ethan-1-one 
• 116795-55-2 1-(1-triphenylmethyl-1H-imidazol-4-yl)-1-ethanone 
• 40243-75-2 2,3-dimethylstyrene 
• 60907-88-2 1-(1-chloroethyl)-2,3-dimethylbenzene 
• 113775-47-6 dexmedetomidine 
• 1021949-47-2 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene 
• 176721-01-0 4-<(2,3-dimethylphenyl)hydroxymethyl>-1-(triphenylmethyl)imidazole 

Downstream Products

• 113775-47-6 dexmedetomidine 
• 145108-58-3 (-)-(R)-4-(1-[2,3-dimethylphenyl]ethyl)-1H-imidazole hydrochloride 

Relevant articles and documents

METHOD FOR PREPARING DEXMEDETOMIDINE

The present invention relates to a method for preparing dexmedetomidine having the following formula (I): or a pharmaceutically acceptable salt and/or solvate thereof, comprising the following successive steps: a) asymmetric hydrogenation of a methylene derivative of the following formula (II): in order to obtain dexmedetomidine, and b) optionally salifying and/or solvating dexmedetomidine in order to obtain a pharmaceutically acceptable salt and/or solvate of dexmedetomidine, wherein the methylene derivative of formula (II) is prepared from a halide of the following formula (V), in which Hal2 represents a halogen atom such as Br, and a cyanoimidazole of the following formula (VI):. The present invention relates also to methods for preparing synthesis intermediates of dexmedetomidine from the halide of formula (V) and the cyanoimidazole of formula (VI), these synthesis intermediates being the methylene derivative of formula (II), an alcohol of the following formula (III), and a ketone of the following formula (IV):.

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 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.

Preparation process of dexmedetomidine hydrochloride for ICU (intensive care unit) sedation and analgesia

The invention discloses a preparation process of dexmedetomidine hydrochloride for ICU (intensive care unit) sedation and analgesia. The preparation process includes the steps: first, stirring and reacting 1-(1-halogenated ethyl)-2, 3-dimethyl benzene and imidazole in ionic liquid under catalysis of ferric trichloride to obtain 4-[1-(2, 3-dimethyl phenyl) ethyl]-1H-imidazole; second, refluxing the 4-[1-(2, 3-dimethyl phenyl) ethyl]-1H-imidazole obtained in the first step and L-(+)-tartaric acid in absolute ethyl alcohol, and performing standing, cooling and suction filtration to obtain dexmedetomidine tartrate; third, stirring the dexmedetomidine tartrate in sodium hydroxide aqueous solution, extracting methylene dichloride, concentrating the solution, stirring the solution in saturated hydrochloric acid methanol solution to obtain the dexmedetomidine hydrochloride. The method is short in reaction time, high in yield, milder in condition and suitable for industrial popularization.

Method for preparing dexmedetomidine hydrochloride for anesthesia and sedation during operation

The invention discloses a method for preparing dexmedetomidine hydrochloride for anesthesia and sedation during an operation. The method comprises the following steps: (a) stirring and reacting 2,3-dimethyl styrene and imidazole in ionic liquid to obtain 4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole in the presence of an iron salt; (b) reacting the 4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole with L-(+)-tartaric acid, and performing suction filtering to obtain dexmedetomidine tartrate; (c) stirring the dexmedetomidine tartrate in an aqueous solution of sodium hydroxide, performing dichloromethane extraction and concentration, and stirring in a saturated hydrochloric acid methanol solution to obtain the dexmedetomidine hydrochloride. According to the method, the ionic liquid is used for alkylation reaction of the imidazole under catalysis of the iron salt, so that the reaction time is effectively shortened, and high yield is achieved; fewer steps are required, and the cost is lower; conditions in each step are mild, use of a large amount of lewis acid is avoided, and easiness for industrial production is achieved.

Method for preparing dexmedetomidine and intermediate thereof

The invention provides a method for preparing dexmedetomidine and an intermediate thereof. Specifically speaking, the method comprises the steps that a compound shown as a formula II (please see the formula in the description) reacts with metal magnesium to prepare a metal magnesium Grignard reagent, and then the metal magnesium Grignard reagent reacts with a compound shown as a formula III (please see the formula in the description). The process has the advantages of being few in step, high in yield, easy to operate, high in product purity and the like and is quite suitable for large-scale industrialized production.

Synthesis and enantiomeric resolution of medetomidine

Medetomidine {4-[l-(2,3-dimethylphenyl)ethyl]-3H-imidazole], 5} is a selective α2-adrenoceptor agonist used in veterinary medicine for its analgesic and sedative properties. It is also an alternative and environmentally acceptable anti-fouling biocide which impedes the settlement of barnacles at nanomolar concentrations and replaces toxic antifouling coatings based on heavy metals. Several syntheses of medetomidine have been reported. The first method for the preparation of 5 and of other related 4-benzylimidazoles was described in a patent starting from 2,3-dimethylbromobenzene as shown in Scheme 1; unfortunately the yields were not reported.

PROCESS FOR THE PREPARATION OF DEXMEDETOMIDINE

The invention discloses a novel process for preparation of dexmedetomidine in higher yield and with enantiomeric purity more than 99%.