145202-66-0

Basic information

• Product Name: Rizatriptan benzoate
• Synonyms: RIZATRIPTAN BENZOATE;N,N-DIMETHYL-5-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1H-INDOLE-3-ETHANAMINE, BENZOATE;n,n-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1h-indol-3-yl]ethylamine benzoate;MK-0462;MK-462;Rizatrimptan Benzoate;Rizatrimptan;Rizatriptan monobenzoate
• CAS NO: 145202-66-0
• Molecular Formula: C22H25N5O2
• Molecular Weight: 391.47
• EINECS: 1312995-182-4
• Product Categories: Antimigraine;Heterocyclic Compounds;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals;Rizatriptan;API;Amines;Heterocycles;MK-462, Maxalt
• Mol File: 145202-66-0.mol

Chemical Properties

• Melting Point: 178-180°C
• Boiling Point: 504.8 ºC at 760 mmHg
• Flash Point: 259.1 ºC
• Appearance: white to beige/
• Density: 1.21 g/cm³
• Vapor Pressure: 2.58E-10mmHg at 25°C
• Refractive Index: 1.645
• Storage Temp.: -20°C Freezer
• Solubility: H2O: ≥5mg/mL
• Merck: 14,8241
• CAS DataBase Reference: Rizatriptan benzoate(CAS DataBase Reference)
• NIST Chemistry Reference: Rizatriptan benzoate(145202-66-0)
• EPA Substance Registry System: Rizatriptan benzoate(145202-66-0)

Safety Data

• Hazard Codes: T
• Statements: 61
• WGK Germany: 3
• Hazardous Substances Data: 145202-66-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Rizatriptan benzoate is used as a pharmaceutical secondary standard for application in quality control, providing a convenient and cost-effective alternative to the preparation of in-house working standards.
Used in Migraine Treatment:
Rizatriptan benzoate is used as an anti-migraine agent for the treatment of migraine headaches. It works by narrowing the blood vessels around the brain and reducing the substances in the body that can cause headache pain. The selective receptor binding is effective in constricting cranial vessels and inhibiting the transmission of nociception, thus providing relief from migraine headaches.
Used in Drug Development:
Rizatriptan benzoate is used in the development of novel drug delivery systems to enhance its applications and efficacy against migraine headaches. Various organic and metallic nanoparticles have been employed as carriers for rizatriptan benzoate delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.
Used in Maxalt:
Rizatriptan benzoate was launched as Maxalt in Mexico for the acute treatment of migraine headaches with or without aura in adults. It is the third in a new generation of triptan migraine drugs to challenge the first-generation product Sumatriptan from Glaxo Wellcome, after Zolmitriptan (Zeneca) and Naratriptan (Glaxo Wellcome).
Chemical Properties:
Rizatriptan benzoate is an off-white solid with good oral bioavailability and a rapid onset of action. The headache relief in humans occurs within 30 to 45 minutes of taking 20 mg. It also relieves nausea and hypersensitivity to noise (phonophobia) and light (photophobia) that are often symptoms accompanying a migraine attack. Maxalt is available as a novel oral formulation of rapidly dissolving tablets or wafers that do not require liquid for ingestion.

References

https://en.wikipedia.org/wiki/Rizatriptan https://pubchem.ncbi.nlm.nih.gov/compound/77997#section=Top http://bodyandhealth.canada.com/drug/getdrug/co-rizatriptan-odt

Originator

Merck & Co (US)

Biochem/physiol Actions

Rizatriptan is a serotonin 5HT-1B/1D-receptor agonist used to treat migraine.

InChI:InChI=1/C15H19N5/c1-19(2)6-5-13-8-17-15-4-3-12(7-14(13)15)9-20-11-16-10-18-20/h3-4,7-8,10-11,17H,5-6,9H2,1-2H3

Upstream product

• 65-85-0 benzoic acid 
• 144034-80-0 rizatriptan 
• 160194-26-3 4-((1H-1,2,4-triazol-1-yl)methyl)-2-iodobenzenamine 
• 160194-39-8 2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl alcohol 
• 199336-63-5 2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl mesylate 
• 61-50-7 N,N-dimethyltryptamine 
• 38662-17-8 2-(dihydroindol-3-yl)-N,N-dimethylethylamine 
• 1586771-53-0 1-(3-(2-(dimethylamino)ethyl)indolin-1-yl)ethanone 
• 1586771-54-1 C₁₇H₂₃N₅O 
• 496-15-1 1-indoline 
• 1092370-41-6 4-(1,2,4-triazol-1-yl-methyl)phenyl-diazonium chloride 
• 144235-64-3 4-(1,2,4-triazolylmethyl)phenylamine hydrochloride 

Relevant articles and documents

Isotope-Edited Infrared Spectroscopy for Efficient Discrimination between Pharmaceutical Salts and Cocrystals

Isotope-edited infrared spectroscopy using carboxylic acids selectively labeled with 13C is proposed herein for the efficient discrimination of pharmaceutical salts and cocrystals, whereby proton-transfer probe vibrations are highlighted by isotope shifts. This new technique can accurately discriminate even a confusing salt from a cocrystal for the traditional method, highlighting the diagnostic peaks. In addition, the established technique also provided the OH in-plane bending vibrations corresponding to intermolecular hydrogen bonding at the carbonyl oxygens of the cocrystals. The technique will accelerate the discrimination, which is a critical process in cocrystal development.

Method for preparing the advantage grips Qu Tan a benzoic acid

The invention discloses a novel preparation method for rizatriptan benzoate. The preparation method uses indoline as a starting material, and performs five-step reaction of triazole methylation, dehydrogenation, side chain formation, reduction and salt formation so as to obtain the rizatriptan benzoate. The innovative point of the method is that a brand-new method for forming an indole ring is adopted, and the defects caused by a fisher indole synthesis method adopted in a conventional course that the impurity content of the product is high, and the purification is difficult. The method has the advantages that the operation is simple and convenient, the reaction condition is mild, no expensive reagent is used, and the product purity is high.

the advantage grips Qu Tan a method of preparing benzoic acid

The invention discloses a novel method for preparing rizatriptan benzoate. According to the method, high-purity rizatriptan benzoate is prepared by performing seven steps of reaction of N,N-methylation, reduction, protection, triazole methylation, deprotection, dehydrogenation and salifying on tryptamine as an initial raw material. The method is characterized in that indole rings are established by using a novel method, and the defects that the product impurity content is high and purification is difficult because of a fisher indole synthesis method used in the conventional process are avoided. The method has the advantages that the operation is simple and convenient, the reaction condition is gentle, no expensive reagents is used, column chromatography purification is not needed, and the product purity is high.

NOVEL PROCESS

The present invention relates to a novel process for the preparation of rizatriptan and its pharmaceutically acceptable salts. It provides a novel process for the preparation of highly pure rizatriptan, which can be easily adopted for commercial production with a high degree of consistency in purity and yield. Subsequently the rizatriptan base prepared can be converted into any suitable pharmaceutically acceptable salt, such as the oxalate, succinate or benzoate salt, for dosage form preparation. The present invention also provides a composition comprising rizatriptan useful for the manufacture of a medicament for the treatment or prevention of migraine.

NOVEL PROCESS

The present invention relates to a novel process for the preparation of rizatriptan and its pharmaceutically acceptable salts. It provides a novel process for the preparation of highly pure rizatriptan, which can be easily adopted for commercial production with a high degree of consistency in purity and yield. Subsequently the rizatriptan base preparedcan be converted into any suitable pharmaceutically acceptable salt, such as the oxalate, succinate or benzoate salt,for dosage form preparation. The present invention also provides a composition comprising rizatriptan useful for the manufacture of a medicament for the treatment or prevention of migraine.

AN IMPROVED PROCESS FOR THE PREPARATION OF RIZATRIPTAN

The present invention relates to an improved process for preparing N,N-dimethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indole-3-ethanamine of Formula I and its pharmaceutically acceptable salts.

PROCESS FOR THE LARGE SCALE PRODUCTION OF RIZATRIPTAN BENZOATE

The present invention provides a method for preparing pure Rizatriptan benzoate having purity more than 99.5% and dimer impurity less than 0.1% comprises, i) Condensation of 1,2,4-Triazole with 4-Nitro benzyl bromide to yield l-(4-nitrophenyl) methyl-1,2,4- triazole ii) Reducing the l-(4-nitrophenyl) methyl-1,2,4-triazole to give l-(4- aminophenyl) methyl-1,2,4-triazole iii) Converting l-(4-aminophenyl) methyl-1,2,4-triazole to l-(4-hydrazinophenyl) methyl-1,2,4-triazole hydrochloride iv) Condensing the hydrazine derivative with 4-(Dimethylamino) butanal diethylacetal to get Rizatriptan and v) Salification of Rizatriptan to Rizatriptan benzoate.

Amorphous rizatriptan benzoate

Rizatriptan benzoate in an amorphous form is disclosed. Also disclosed is a process for preparing rizatriptan benzoate substantially in amorphous form comprising the steps of (a) preparing a solvent solution comprising non-amorphous rizatriptan benzoate a

IMPROVED PROCESS FOR THE PREPARATION OF RIZATRIPTAN BENZOATE

Present invention discloses an improved and commercially viable process for the preparation of rizatriptan benzoate of formula (I). According to the present process the hydrazone intermediate derived from the phenylhydrazine of formula- (III) and 4- dimethylaminobutyraldehyde diethyl acetal is gradually heated to 60-70 °C in aqueous sulfuric acid medium and maintained for 3-4hr to get rizatriptan with less dimeric impurity of formula (X). The resultant rizatriptan is isolated and converted into the pharmaceutically acceptable benzoate salt. Present process produces less percentage of dimeric (less than 3 %) or polymeric impurities compared to the prior art process and more yield of rizatriptan. Rizatriptan benzoate produced according to the present process has more than 99.5 % purity with less than 0.1% dimeric impurity of formula (X) by HPLC. Rizatriptan benzoate is useful for the treatment of migraine.

NOVEL CRYSTALLINE FORMS OF RIZATRIPTAN BENZOATE

Present invention relates to three novel crystalline forms, named as Form I, II, and III of rizatriptan benzoate, process for their preparation and pharmaceutical compositions containing them.