181183-52-8

Basic information

• Product Name: ALMOTRIPTAN
• Synonyms: BUTANEDIOIC ACID, HYDROXY-, COMPD WITH 1-[[[3-[2-(DIMETHYLAMINO)ETHYL]-1H-INDOL-5-YL]METHYL]SULFONYL]PYRROLIDINE;ALMOTRIPTAN MALATE;AlmotriptanMaleate;1-[[[2-(Dimethyl-amino)ethyl]-1H-indol-5-yl]methyl]sulfonyl]pyrrolidine Malate;1-[[3-(2-dimethylaminoethyl)-5-indolyl]methanesulphonyl]pyrrolidine Malate;LAS-31416 Malate;N,N-Dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indol-3-yl]ethanamine;Almotriptan
• CAS NO: 181183-52-8
• Molecular Formula: C₄H₆O₅*C₁₇H₂₅N₃O₂S
• Molecular Weight: 469.56
• EINECS: 1806241-263-5
• Product Categories: Pharmaceutical material and intermeidates;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals;API;Inhibitors
• Mol File: 181183-52-8.mol

Chemical Properties

• Melting Point: 170-172°C
• Boiling Point: 538.7 °C at 760 mmHg
• Flash Point: 279.6 °C
• Appearance: Pale yellow solid
• Density: 1.27g/cm3
• Vapor Pressure: 1.13E-11mmHg at 25°C
• Storage Temp.: -20°C Freezer
• Solubility: Basic Alcohol (Very Slightly), DMSO (Slightly), Methanol (Slightly, Heated)
• CAS DataBase Reference: ALMOTRIPTAN(CAS DataBase Reference)
• NIST Chemistry Reference: ALMOTRIPTAN(181183-52-8)
• EPA Substance Registry System: ALMOTRIPTAN(181183-52-8)

Safety Data

• Hazardous Substances Data: 181183-52-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Almotriptan is used as an anti-migraine agent for the treatment of migraine headaches. It acts as a serotonin 5HT1B/1D-receptor agonist, leading to vasoconstriction of the brain blood vessels and affecting the redistribution of blood flow, which helps in stopping pain signals from being sent to the brain and suppressing the release of certain natural substances that cause pain, nausea, and other migraine symptoms.
Used in Migraine Treatment:
Almotriptan is used as a treatment for migraine headaches, specifically targeting the serotonin 5-HT1B and 5-HT1D receptors. It induces contractions in isolated canine saphenous veins and increases carotid vascular resistance in anesthetized cats without increasing blood pressure or heart rate. Formulations containing almotriptan have been effectively used in the treatment of migraine headaches. However,

References

https://en.wikipedia.org/wiki/Almotriptan https://www.drugbank.ca/drugs/DB00918

Originator

Almogran ,Lundbeck

Therapeutic Function

Migraine therapy

Biochem/physiol Actions

Almotriptan is a serotonin 5HT-1B/1D-receptor agonist used to treat migraine. Almotriptan has low nanomolar affinity for the 5-HT(1B) and 5-HT(1D) receptors while affinity for 5-HT receptors other than 5-HT(1B/1D) is substantially lower. Affinity for 5-HT(7) and 5-HT(1A) receptors was approximately 40 and 60 times lower than that for 5-HT(1B/1D) receptors, respectively.

InChI:InChI=1/C17H25N3O2S.C4H6O5/c1-19(2)10-7-15-12-18-17-6-5-14(11-16(15)17)13-23(21,22)20-8-3-4-9-20;5-2(4(8)9)1-3(6)7/h5-6,11-12,18H,3-4,7-10,13H2,1-2H3;2,5H,1H2,(H,6,7)(H,8,9)

Synthetic route

malic acid (617-48-1) + almotriptan (154323-57-6) → almotriptan malate (181183-52-8)

Conditions	Yield
In methanol for 1h; Product distribution / selectivity; Reflux;	99.51%
In methanol at 40℃;	93%
In methanol at 20 - 40℃; for 2h; Large scale;	93%

almotriptan 2-hydroxy benzoate (922735-96-4) + malic acid (617-48-1) → almotriptan malate (181183-52-8)

Conditions	Yield
Stage #1: almotriptan 2-hydroxy benzoate With ammonia In methanol; water; ethyl acetate for 1h; Stage #2: malic acid In methanol at 25℃; for 4.5h; Product distribution / selectivity; Heating / reflux;
Stage #1: almotriptan 2-hydroxy benzoate With ammonia In water; ethyl acetate at 25 - 30℃; for 1h; Stage #2: malic acid In methanol at 25 - 30℃; for 4.5h; Product distribution / selectivity; Heating / reflux;

N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonyl-methyl)-1H-indol-3-yl]-ethanaminium semioxalate (922735-94-2) + malic acid (617-48-1) → almotriptan malate (181183-52-8)

Conditions	Yield
Stage #1: N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonyl-methyl)-1H-indol-3-yl]-ethanaminium semioxalate With ammonia In water; ethyl acetate for 1h; Stage #2: malic acid In methanol at 20℃; for 4.5h; Product distribution / selectivity; Heating / reflux;
Stage #1: N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonyl-methyl)-1H-indol-3-yl]-ethanaminium semioxalate With ammonia In water; ethyl acetate for 1h; Stage #2: malic acid In methanol at 25 - 35℃; for 4.5h; Product distribution / selectivity; Heating / reflux;

Upstream product

• 922735-94-2 N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonyl-methyl)-1H-indol-3-yl]-ethanaminium semioxalate 
• 617-48-1 malic acid 
• 922735-96-4 almotriptan 2-hydroxy benzoate 
• 154323-57-6 almotriptan 

Relevant articles and documents

Pharmaceutical composition comprising almotriptan malate having uniform drug distribution and potency

The present invention relates to tablets comprising almotriptan malate and mannitol, wherein the mannitol is in crystalline form and the bulk density of the mannitol is below 0.75 g/ml. The present invention also relates to a specific crystalline form of

PROCESS FOR THE PREPARATION OF 1-[[[3-[2-(DIMETHYLAMINO)ETHYL]-1H-INDOL-5-YL]METHYL]SULFONYL] PYRROLIDINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS

The present invention relates to an improved process for the preparation of 1-[[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] methyl] sulfonyl]pyrrolidine compound of formula- 1 and its pharmaceutically acceptable salts.

NOVEL PROCESS

The present invention relates to a novel process for the preparation of almotriptan and pharmaceutically acceptable salts thereof, which affords product conveniently and efficiently with commercially acceptable yields and purity. The present invention also relates to a novel synthetic intermediate used in the process.

Process for the Preparation of Almotriptan

The present invention encompasses a method for the preparation of Almotriptan and its pharmaceutically acceptable salts comprises, i) Methylation of 3-[5-(1-Pyrrolidinyl sulfonyl methyl) 1H-indol-yl]ethane amine ii) Treating crude Almotriptan with a hydro

METHOD FOR THE PREPARATION OF HIGH PURITY ALMOTRIPTAN

A method for the preparation and purification of the substance of formula (I), i.e. 3-[2- (dimethylamino)ethyl]-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole, which comprises (a) conversion of 4-(1-pyrrolidinylsulfonylmethyl)phenylhydrazine of formula (III) by reaction with an organic or inorganic acid to a salt that is insoluble or poorly soluble in water, which is converted to 3-(2-aminoethyl)-5-(1-pyrrolidinylsulfonylmethyl)indole of formula (VII), which is further converted without isolation to a solution of the almotriptan base, which provides a crystalline salt of almotriptan with an organic or inorganic acid; (b) conversion of the salt of almotriptan to the almotriptan base, which separates from the solution in the crystalline form; (c) purification of the almotriptan base by crystallization from an organic solvent.

A PROCESS FOR THE PREPARATION OF ALMOTRIPTAN

The present invention encompasses a method for the preparation of Almotriptan and its pharmaceutically acceptable salts comprises, i) Methylation of 3-[5-(l- Pyrrolidinyl sulfonyl methyl) lH-indol-yl] ethane amine ii) Treating crude Almotriptan with a hyd

Crystalline forms of almotriptan and processes for their preparation

Crystalline forms of almotriptan and almotriptan malate are disclosed. Processes for their preparation and pharmaceutical compositions containing the same are also disclosed. The amorphous form of almotriptan malate, processes for its preparation and a pharmaceutical composition containing the same are also disclosed