59467-77-5

Basic information

• Product Name: Climazolam
• Synonyms: Climazolam;8-Chloro-6-(2-chlorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine;Ro-21-3982
• CAS NO: 59467-77-5
• Molecular Formula: C₁₈H₁₃Cl₂N₃
• Molecular Weight: 342.22
• Mol File: 59467-77-5.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 522.7°C at 760 mmHg
• Flash Point: 269.9°C
• Appearance: /
• Density: 1.38g/cm³
• Vapor Pressure: 5.07E-11mmHg at 25°C
• Refractive Index: 1.692
• PKA: 6.05±0.40(Predicted)
• CAS DataBase Reference: Climazolam(CAS DataBase Reference)
• NIST Chemistry Reference: Climazolam(59467-77-5)
• EPA Substance Registry System: Climazolam(59467-77-5)

Safety Data

• Hazardous Substances Data: 59467-77-5(Hazardous Substances Data)

Usage

Description

Climazolam, also known as Ro21-3982, is a potent imidazobenzodiazepine derivative used in veterinary medicine as an anesthetic. It was developed by Hoffman-LaRoche and introduced as a veterinary medicine by the Swiss Pharmaceutical company Grüb under the tradename Climasol. Climazolam is similar in structure to midazolam and diclazepam and is known for its rapid onset of effect following intravenous administration.

Uses

Used in Veterinary Medicine:
Climazolam is used as an anesthetic agent for various animals, including dogs, cattle, sheep, horses, and dogs. It is particularly effective when used in combination with other anesthetic agents such as ketamine. In horses, the combination of climazolam and ketamine has been used by constant rate infusion (CRI) to produce total intravenous anesthesia (TIVA), with climazolam being reversed with sarmazenil at the end of surgery to facilitate a rapid recovery.
Used in Anesthetic Combinations:
Climazolam is used as a component of anesthetic combinations to provide effective anesthesia for surgical procedures in animals. It is often combined with other anesthetic agents to enhance the overall anesthetic effect and improve the safety and efficacy of the procedure.
Used in Dogs:
Climazolam (1.0–1.5 mg/kg) has been used in combination with fentanyl (0.005–0.015 mg/kg) for anesthesia in dogs, providing a balanced anesthetic regimen that ensures proper sedation and pain management during surgical procedures.

Indications

Climazolam: an injectable benzodiazepine approved in Europe for anesthesia in dogs and cats, for example, as premedication with an opioid or for induction with ketamine.Climazolam is a possible alternative to midazolam, but its use will require a relaxing of the import regulations by Health Canada and of the minimum practice standards of the OMVQ (which encourages the use of approved drugs), since it is not approved in Canada.If climazolam were approved in Canada (it is approved in Europe for dogs and cats), it could replace diazepam or midazolam in combination with ketamine or other induction agents.

Overdosage

Dose (mg/kg): 0.5–2.0 IM, IVComments: In combination with an opioid or anaesthetic agent

InChI:InChI=1/C18H13Cl2N3/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13/h2-9H,10H2,1H3

Synthetic route

8-chloro-6-(2-chlorophenyl)-3a,4-dihydro-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (59467-76-4) → 8-chloro-6-(2-chloro-phenyl)-1-methyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine (59467-77-5)

Conditions	Yield
With enzyme-containing bacterial cell from Arthrobacter sp. at 25℃; for 35h; pH=6.5; Concentration; Enzymatic reaction;	89%
With manganese dioxide In toluene

2-aminomethyl-7-chloro-5-(2-chlorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine → 8-chloro-6-(2-chloro-phenyl)-1-methyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine (59467-77-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 3 h / Sonication 2: enzyme-containing bacterial cell from Arthrobacter sp. / 35 h / 25 °C / pH 6.5 / Enzymatic reaction View Scheme

Upstream product

• 59467-76-4 8-chloro-6-(2-chlorophenyl)-3a,4-dihydro-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine 

Relevant articles and documents

Benzodiazepines method for the preparation of compound

The invention relates to a method for preparing benzodiazepine compounds, and discloses a method for preparing 8-R2-6-(2-R1-phenyl)-1-methyl-3a,4-dihydro-3H-imidazo[1,5-a][1,4] benzodiazepine (midbody II) and 8-R2-6-(2-R1-phenyl)-1-methyl-4H-imidazo[1,5-a][1,4] benzodiazepine (product III), wherein R is hydrogen, fluorine, chlorine, bromine or iodine; R2 is fluorine, chlorine, bromine or iodine. The midbody II is prepared from 7-R2-5-(2-R1-phenyl)-2-aminomethyl-2,3-dihydro-1H-[1,4] benzodiazepine and triethyl orthoacetate as raw materials through ultrasonic reaction; the product III is prepared by performing enzyme dehydrogenation on the midbody II. By adopting the technical scheme of the invention, the dehydrogenation reaction selectivity is improved, and the reaction yield is improved.

Process for the synthesis of 4H-imidazo[1,5-a][1,4]benzodiazepines, in particular midazolam and salts thereof

The present invention refers to a process for the preparation of 4H-imidazo[1,5-a] [1,4]benzodiazepines, in particular Midazolam, through an efficient and selective decarboxylation reaction of the derivative compound of the 5-aminomethyl-1-phenyl-1H-imidazole-4-carboxylic acid of formula (II) avoiding the formation of the 6H-imidazo[1,5-a][1,4]benzodiazepines by-products and the ensuing process for the isomerisation of a 4H-imidazo[1,5-a][1,4]benzodiazepine product.