144034-80-0

Basic information

• Product Name: Rizatriptan
• Synonyms: n,n-dimethyl-5-(1h-1,2,4-triazol-1-ylmethyl)-1h-indole-3-ethanamine;n,n-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1h-indol-3-yl]ethanamine;RIZATRIPTAN;diMethyl({2-[5-(1H-1,2,4-triazol-1-ylMethyl)-1H-indol-3-yl]ethyl})aMine;2-(5-((1H-1,2,4-Triazol-1-yl)Methyl)-1H-indol-3-yl)-N,N-diMethylethanaMine;1H-Indole-3-ethanaMine,N,N-diMethyl-5-(1H-1,2,4-triazol-1-ylMethyl)-;144034-80-0;Rizatriptan###144034-80-0
• CAS NO: 144034-80-0
• Molecular Formula: C₁₅H₁₉N₅
• Molecular Weight: 269.34486
• Product Categories: NORVASC;Other APIs
• Mol File: 144034-80-0.mol

Chemical Properties

• Melting Point: 178-180°C
• Boiling Point: 504.8 °C at 760 mmHg
• Flash Point: 259.1 °C
• Appearance: /
• Density: 1.21 g/cm³
• Vapor Pressure: 2.58E-10mmHg at 25°C
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 16.98±0.30(Predicted)
• Water Solubility: 42 mg/mL
• CAS DataBase Reference: Rizatriptan(CAS DataBase Reference)
• NIST Chemistry Reference: Rizatriptan(144034-80-0)
• EPA Substance Registry System: Rizatriptan(144034-80-0)

Safety Data

• Hazardous Substances Data: 144034-80-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Rizatriptan is used as an acute migraine drug for the rapid relief of migraine symptoms. It targets the serotonin 5-HT1B and 5-HT1D receptor subtypes, providing effective treatment for migraine sufferers.
Used in Neurology:
As a Ca channel blocker, Rizatriptan is used to alleviate the pain and discomfort associated with migraines by blocking the release of calcium ions, which play a role in the constriction of blood vessels and the transmission of pain signals.

Drug interactions

Potentially hazardous interactions with other drugs Antidepressants: increased risk of CNS excitation with citalopram - avoid; risk of CNS toxicity with MAOIs, moclobemide and linezolid - avoid for 2 weeks after discontinuation of MAOI and moclobemide; possibly increased serotonergic effects with duloxetine and venlafaxine; increased serotonergic effects with St John’s wort - avoid. Dapoxetine: possible increased risk of serotonergic effects - avoid for 2 weeks after stopping 5HT1 agonists. Ergot alkaloids: increased risk of vasospasm - avoid. Propranolol: rizatriptan levels increased, reduce dose of rizatriptan to 5 mg (max 10 mg in 24 hours).

Metabolism

The main route of rizatriptan metabolism is via oxidative deamination by monoamine oxidase-A (MAO-A) to the indole acetic acid metabolite, which is not pharmacologically active. N-monodesmethyl-rizatriptan, a metabolite with activity similar to that of parent compound, is formed to a minor degree, but does not contribute significantly to the pharmacodynamic activity of rizatriptan. Less than 1% is excreted in the urine as active N-monodesmethyl metabolite.

InChI:InChI=1/C15H19N5.C7H6O2/c1-19(2)6-5-13-8-17-15-4-3-12(7-14(13)15)9-20-11-16-10-18-20;8-7(9)6-4-2-1-3-5-6/h3-4,7-8,10-11,17H,5-6,9H2,1-2H3;1-5H,(H,8,9)

Upstream product

• 124-40-3 dimethyl amine 
• 199336-63-5 2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl mesylate 
• 50-00-0 formaldehyd 
• 144035-23-4 2-<5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl>ethylamine 
• 19718-92-4 4-(N,N-dimethylamino)butyraldehyde dimethyl acetal 
• 154748-67-1 (4-[1,2,4]triazol-1-ylmethylphenyl)hydrazine hydrochloride 
• 290-87-9 1,3,5-Triazine 
• 119192-10-8 4-(1H-1,2,4-triazol-1-ylmethyl)aniline 
• 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 
• 658697-16-6 3-(2-dimethylaminoethyl)-5-[1,2,4]triazol-1-ylmethyl-1H-indol-2-carboxylic acid 
• 154748-67-1 1-(4-hydrazinophenyl)-methyl-1,2,4-triazole dihydrochloride 
• 144235-64-3 1-(4-aminophenyl)methyl-1,2,4-triazole dihydrochloride 
• 145202-66-0 rizatriptan benzoate 

Downstream Products

• 145202-66-0 rizatriptan benzoate 
• 260435-42-5 N,N-dimethyl-5-(1H-1,2,4-triazol-1-yl-methyl)-1H-indol-3-ethanamine N-oxide 

Relevant articles and documents

A novel and convenient route for the construction of 5-((1H-1,2,4-triazol- 1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan

In this study, a novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles (8) is presented starting from (1H-1,2,4-triazol-1-yl)methanol (5) and indolines (6) under 98% H 2SO4 at room temperature for 4-24 h, followed by deacetylation and dehydrogenation. Based on this finding, a novel route to synthesize Rizatriptan starting from tryptamine was designed and accomplished with 48.5% overall yield in 6 steps. Compared with operational art, the new route afforded higher yield and more pure products requiring no chromatographic purification, which may further be applied in industrialization.

Synthesis of the 5-HT1D receptor agonist MK-0462 via a Pd-catalyzed coupling reaction

Application of a palladium-catalyzed coupling between 3 and 5a to the synthesis of the novel 5-HT1D receptor agonist MK-0462 (1), a potential anti-migraine drug, is described.

Rizatriptan preparation method

The invention discloses a rizatriptan preparation method, wherein 5-methyltryptamine is used as a raw material, and five steps of amino methylation, bromination, Boc amino protection, triazole substitution and Boc deprotection are performed to obtain rizatriptan. According to the present invention, the existing indole synthesis method is avoided by using 5-methyltryptamine as the starting raw material, the used reagent is environmentally friendly, and the preparation method has characteristics of simpleness, mild condition and simple post-treatment, is suitable for industrial promotion, and isthe completely-new rizatriptan preparation method.

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.

Aqueous Titanium Trichloride Promoted Reductive Cyclization of o-Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine

Treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature afforded indoles through a formal reductive C(sp2)-H amination process. A range of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano, hydroxy, and amino groups were tolerated. From β,β-disubstituted o-nitrostyrenes, 2,3-disubstituted indoles were formed by a domino reduction/cyclization/migration process. Mild conditions, simple experimental procedure, ready accessibility of the starting materials and good to excellent yields characterize the present transformation. The methodology was used as a key step in a concise synthesis of rizatriptan and a formal total synthesis of aspidospermidine. Mild and efficient treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature afforded indoles through a formal reductive C(sp2)-Hamination process. A concise synthesis of a marketed drug (rizatriptan) and a formal total synthesis of aspidospermidine featuring this novel N-heterocyclization process are reported.

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.

A new synthesis of rizatriptan based on radical cyclization

A new methodology useful for preparation of indole derivatives bearing a 2-(dialkylamino)-ethyl substituent at the 3-position has been developed. Application of this methodology to the synthesis of N,N-dimethyl-2-{5-[(1H-1,2, 4-triazol-1-yl)methyl]-1H-indol-3-yl}ethan-1-amine (rizatriptan; 3) is described. The key reaction step is based on the radical cyclization of N-[4-(dimethylamino)but-2-yn-1-yl]-N-(2-iodo-4-[(1H-1,2,4-triazol-1-yl)methyl] phenyl}-acetamide (21), easily available by the Mannich reaction, and subsequent isomerization of the primarily formed methylidene derivative 22.

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.