208464-41-9

Basic information

• Product Name: (S)-5-broMo-3-((1-Methylpyrrolidin-2-yl)Methyl)-1H-indole
• Synonyms: (S)-5-broMo-3-((1-Methylpyrrolidin-2-yl)Methyl)-1H-indole;5-bromo-3-[[(2S)-1-methyl-2-pyrrolidinyl]methyl]-1H-Indole
• CAS NO: 208464-41-9
• Molecular Formula: C14H17BrN2
• Molecular Weight: 293.20218
• Mol File: 208464-41-9.mol

Chemical Properties

• Appearance: /
• Solubility: DCM, Methanol
• CAS DataBase Reference: (S)-5-broMo-3-((1-Methylpyrrolidin-2-yl)Methyl)-1H-indole(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-5-broMo-3-((1-Methylpyrrolidin-2-yl)Methyl)-1H-indole(208464-41-9)
• EPA Substance Registry System: (S)-5-broMo-3-((1-Methylpyrrolidin-2-yl)Methyl)-1H-indole(208464-41-9)

Safety Data

• Hazardous Substances Data: 208464-41-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-5-broMo-3-((1-Methylpyrrolidin-2-yl)Methyl)-1H-indole is used as an intermediate in the synthesis of ent-Eletriptan (E505005), which is an enantiomeric impurity of the serotonin 5-HT1B/1D receptor agonist Eletriptan (E505000). This application is crucial for the development of drugs that can effectively target and modulate the activity of serotonin receptors, which are involved in various physiological processes, including mood regulation, appetite, and pain perception.
In the synthesis of Eletriptan, (S)-5-broMo-3-((1-Methylpyrrolidin-2-yl)Methyl)-1H-indole serves as a key building block, allowing chemists to create the final drug product with the desired stereochemistry and biological activity. By controlling the enantiomeric purity of Eletriptan, the compound can be more effectively used in the treatment of migraines and other conditions related to serotonin receptor dysregulation.
Furthermore, the compound may also have potential applications in the development of other drugs targeting different receptors or biological pathways. Its unique structure and functional groups make it a versatile starting material for the synthesis of various pharmaceutical compounds, contributing to the advancement of novel therapeutic agents in the pharmaceutical industry.

Upstream product

• 143322-56-9 (R)-3-[(N-benzyloxycarbonylpyrrolidin-2-yl)carbonyl]-5-bromo-1H-indole 
• 1196663-29-2 5-bromo-3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-1H-indole ethanedioate 
• 199659-03-5 3-(N-benzyloxycarbonylpyrrolidin-2S-ylcarbonyl)-5-bromo-1H-indole 
• 1353991-68-0 (R)-2-(5-bromo-1H-indole-3-carbonyl)pyrrolidine-1-carboxylic acid phenyl ester 
• 1353991-67-9 (R)-2-chlorocarbonylpyrrolidine-1-carboxylic acid phenyl ester 
• 105370-80-7 (R)-pyrrolidine-1,2-dicarboxylic acid 1-phenyl ester 
• 61350-62-7 N-benzyloxycarbonyl-D-proline acid chloride 
• 6404-31-5 Z-D-proline 

Downstream Products

• 208464-80-6 C₂₆H₂₈N₂O₂ 
• 208465-04-7 (S)-5-(1-aza-1-tert-butoxycarbonylcyclohex-3-en-4-yl)-3-[(N-methylpyrrolidin-2-yl)methyl]-1-benzoylindole 
• 208464-81-7 C₂₆H₂₈N₂O₂ 
• 209682-64-4 5-ethyl-3-{[1-methylpyrrolidin-2-yl]methyl}-1H-indole 
• 180637-89-2 (R)-5-[(2-phenylsulfonyl)ethenyl]-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole 
• 209682-64-4 (R)-3-[(1-methyl-2-pyrrolidinyl)-methyl]-5-ethyl-1H-indole 
• 143322-55-8 (R)-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole 
• 143322-58-1 eletriptan 

Relevant articles and documents

PROCESS FOR PREPARING PURE 5-BROMO-3-[(R)-1-METHYL-PYRROLIDIN-2-YLMETHYL]-1H-INDOLE, INTERMEDIATE FOR ELETRIPTAN

Disclosed is a process for preparing pure 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole (BIP), an intermediate for eletriptan. The process comprises forming organic acid salt of BIP and then regenerating the said salt to give pure BIP.

PROCESS FOR THE PREPARATION OF 5-SUBSTSITUTED INDOLE DERIVATIVE

The present invention relates to an improved and industrially advantageous process for preparation of eletri tan of formula I,or pharmaceutically acceptable salts thereof from bromo indole intermediate of formula II, through isolation of N-acetylated bromo indole intermediate of formula III, to elude carrying forward of impurities to next stage. The present invention relates to process for the preparation of 5-bromo-3-[(R)-l-methyl-pyrrolidin-2- lmeth l -lH-indol of formula II, a key intermediate for the synthesis of eletriptan or pharmaceutically acceptable salts thereof, through novel keto carbamate intermediate. The present invention also relates to novel process for the preparation of a-form of eletriptan hydrobromide.

PROCESS FOR PREPARATION OF ELETRIPTAN AND SALT THEREOF

The present invention relates to an improved process for the preparation of 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethyl]-1H-indole or pharmaceutically acceptable salts thereof, particularly 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethyl]-1H-indole hydrobromide (Eletriptan hydrobromide). The present invention further relates to novel polymorphs of 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethenyl]-1H-indole hydrobromide and process for preparation thereof.

SYNTHESIS OF 3--5-[2-(PHENYLSULFONYL)ETHYL]-1H-INDOLE

The present invention refers to the synthesis of 3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-5-[2-(phenylsulfonyl)ethyl]-1H-indole, a drug known by the name Eletriptan, or of its salts. In particular, the present invention regards a process for the synthesis of Eletriptan or of its salt, comprising the following steps: a) Salifying the intermediate of Formula (6), using a dicarboxylic acid to obtain a derived salt; b) Optionally, purifying said raw salt obtained according to step a) by solvent crystallization to obtain a purified salt of the intermediate of Formula (6); c) Converting said salt of the intermediate of formula (6) according to step a) or said purified salt according to step b) into an intermediate of formula (10); d) Converting the intermediate of Formula (10) into Eletriptan or its salt.

SYNTHESIS OF 3-{[(2R)-1-METHYLPYRROLIDIN-2-YL]METHYL}-5-[2-(PHENYLSULFONYL)ETHYL]-1H-INDOLE

The present invention refers to the synthesis of 3-{[(2R)-l-methylpyrrolidin-2-yl]methyl}-5-[2-(phenylsulfonyl)ethyl]-lH-indole, a drug known by the name Eletriptan, or of its salts. In particular, the present invention regards a process for the synthesis of Eletriptan or of its salt, comprising the following steps: a) Salifying the intermediate of Formula (6), using a dicarboxylic acid to obtain a derived salt; b) Optionally, purifying said raw salt obtained according to step a) by solvent crystallization to obtain a purified salt of the intermediate of Formula (6); c) Converting said salt of the intermediate of formula (6) according to step a) or said purified salt according to step b) into an intermediate of formula (10); d) Converting the intermediate of Formula (10) into Eletriptan or its salt.

Salts of (R)-5-(2phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole, 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole and of eletriptan

The present invention relates to salts of (R)-5-(2-phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole of the formula: wherein HX is an acid selected from para-toluene sulfonic acid, benzene sulphonic acid, trifluoroacetic acid, methane sulphonic acid, formic acid and succinic acid; and to processes of preparing and using such salts.

Process for preparing 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole

The invention encompasses a process for preparing 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole comprising reacting (R)-2-(5-bromo-1H-indole-3-carbonyl)-pyrrolidine-1-carboxylic acid benzyl ester with a reducing agent selected from the group consisting of sodium dihydro-bis(2-methoxyethoxy)aluminate, lithium tris[(3-ethyl-3-pentyl)oxy]aluminohydride, lithium tri-tert-butoxyaluminum hydride and diisobutylaluminium hydride. 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole is a key intermediate for preparing eletriptan and its salts thereof.

5-CYCLO INDOLE COMPOUNDS AS 5-HT1D RECEPTOR LIGANDS

Described herein are compounds selective for a 5-HT1D-like receptor, which have general formula (I), wherein A is selected from a six-membered, non-aromatic, optionally substituted carbocycle and a six-membered, non-aromatic, optionally substituted heterocycle having one or two heteroatoms selected from O, S, SO, SO2 and NR; R is selected from H and OH; n is 0 or 1 as permitted by chemical structure; R is selected from CRRCH2NRR or a group of formula (II), (III) or (IV); R is selected from H and benzoyl; R is selected from H, loweralkyl, benzyl, loweralkylcarbonyl, loweralkylaminocarbonyl; loweralkylaminothiocarbonyl, loweralkanoyl, loweralkylaminoimide and loweralkoxy-substituted loweralkylene; R and R are independently selected from H, loweralkoxy and hydroxy; R and R are independently selected from H and loweralkyl or R and R form an alkylene bridge which, together with the nitrogen atom to which they are attached, creates an optionally substituted 3- to 6-membered ring; ----- denotes a single or double bond; and R, R and R are independently selected from H and loweralkyl. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of a 5-HT1D-like receptor is implicated, such as migraine.

(R)-3-(N-Methylpyrrolidin-2-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl) -1H-indole derivatives as high affinity h5-HT1B/1D ligands

A series of (R)-3-(N-methylpyrrolidin-2-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl) -1H-indole derivatives (2) have been prepared using parallel synthesis, and their structure-activity relationship studied. High affinity human 5-HT 1B/1D (h5-HT1B/1D) ligands have been identified.

Pyrrolidine-indole compounds having 5-HT6 affinity

Described herein are compounds with affinity for the 5-HT 6 receptor, which have the general formula: STR1 wherein: R 1 is selected from the group consisting of H and C 1-4 alkyl;R 2 is selected from the group consisting of H, C 1-4 alkyl and benzyl;R 3 is selected from the group consisting of COR 5, SO 2 R 5, CONHC 1-4 alkyl and C(S)SR 6 ;R 4a is selected from the group consisting of H, OH, halo, C 1-4 alkyl and C 1-4 alkoxy;R 4b is selected from the group consisting of H, hydroxy, halo, C 3-7 cycloalkyloxy, C 1-4 alkoxy, C 1-4 alkyl, benzyloxy, phenoxy, trifluoromethyl, trifluoromethoxy and vinyl;R 4c is selected from the group consisting of H, OH, halo, C 1-4 alkyl and C 1-4 alkoxy;R 4d is selected from the group consisting of H, OH, halo, C 1-4 alkyl and C 1-4 alkoxy;R 5 is selected from the group consisting of phenyl, pyridyl, thienyl, quinolinyl and naphthyl which are optionally substituted with 1-4 substituents selected from C 1-4 alkoxy, C 1-4 alkyl, halo, nitro, trifluoromethyl, trifluoromethoxy, 1,2-methylenedioxy, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl and C 1-4 alkylS--; andR 6 is selected from C 1-4 alkyl, allyl, propargyl and optionally substituted benzyl wherein the benzyl group is optionally substituted with 1-4 substituents selected from cyano, C 1-4 alkyl and halo.Also described is the use of these compounds as pharmaceuticals to treat indications where inhibition of the 5-HT 6 receptor is implicated, such as schizophrenia.