- PROCESS FOR PREPARING (( R)-3-[(-1-METHYLPYRROLIDIN-2-YL)METHYL]-5-(2-PHENYLSULFONYLETHYL)-1H-INDOLE
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The present invention provides an efficient and environmentally friendly process for the preparation of (R)-3-[(-1-methylpyrrolidin-2-yl)methyl]-5-(2-phenylsulfonylethyl)-1H- indole (eletriptan) and pharmaceutically acceptable salts thereof, in good yield and high purity, which is also suitable for industrial scale applications. The present invention also provides new acid addition salts of (R)-3-[(-1-methylpyrrolidin-2-yl)methyl]-5-(2- phenylsulfonylethyl)-1H-indole, which are also suitable for preparing (R)-3-[(-1- methylpyrrolidin-2-yl)methyl]-5-(2-phenylsulfonylethyl)-1H-indole and pharmaceutically acceptable salts thereof, in good yield and high purity. The present invention additionally provides tert-butylcarbonyl protected precursors to the compound eletriptan.
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- PROCESS FOR THE PREPARATION OF 5-SUBSTSITUTED INDOLE DERIVATIVE
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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.
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- Synthesis of compounds related to the anti-migraine drug eletriptan hydrobromide
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Eletriptan hydrobromide (1) is a selective serotonin (5-HT1) agonist, used for the acute treatment of the headache phase of migraine attacks. During the manufacture of eletriptan hydrobromide the formation of various impurities were observed and identified by LC-MS. To control the formation of these impurities during the preparation of active pharmaceutical ingredients, the structure of the impurities must be known. Major impurities of the eletriptan hydrobromide synthesis were prepared and characterized by using various spectroscopic techniques, i.e., mass spectroscopy, FTIR , 1H NMR, 13C NMR/DEPT, and further confirmed by co-injection in HPLC. The present study will be of great help in the synthesis of highly pure eletriptan hydrobromide related compounds.
- Madasu, Suri Babu,Vekariya, Nagaji Ambabhai,Hari Kiran,Gupta, Badarinadh,Islam, Aminul,Douglas, Paul S.,Babu, Korupolu Raghu
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p. 1400 - 1405
(2012/11/07)
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- Investigational study into the formation of methoxy derivative and other impurities during the optimization of eletriptan hydrobromide
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During the process development of eletriptan hydrobromide, we have observed formation of an unknown impurity in the final product at enhanced levels which was identified as a methoxy substituted derivative on the side chain of the product. The present work involves detailed optimization studies directed toward the development of an efficient process for the commercial production of eletriptan hydrobromide substantially free from the methoxy impurity and other impurities.
- Kumar, U. Sampath,Sankar, V. Ravi,Rao, M. Malleswara,Jaganathan,Buchi Reddy
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p. 1917 - 1920
(2013/03/13)
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- PROCESS FOR PREPARATION OF ELETRIPTAN AND SALT THEREOF
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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.
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- HIGHLY PURE ELETRIPTAN OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF SUBSTANTIALLY FREE OF ELETRIPTAN N-OXIDE IMPURITY
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Provided herein is an impurity of eletriptan, eletriptan N-oxide, (R)-5-[2- (phenylsulfonypethyl]-3-[(1-methyl-2-pyrrolidinyl-N-oxide)methyl]-1H-indole, and a process for the preparation and isolation thereof. Provided further herein is a highly pure eletriptan or a pharmaceutically acceptable salt thereof substantially free of eletriptan N-oxide impurity, processes for the preparation thereof, and pharmaceutical compositions comprising highly pure eletriptan or a pharmaceutically acceptable salt thereof substantially free of eletriptan N-oxide impurity.
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Page/Page column 8
(2012/02/06)
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- PROCESS FOR PREPARING ELETRIPTAN HYDROBROMIDE HAVING α-FORM
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A process for preparation of eletriptan hydrobromide having α-form of formula (I) is described that includes reducing 3-((R)-1-methylpyrrolidin-2-yl)methyl)-5-((E)-2-(phenylsulfonyl)vinyl)-1H-indole of formula (II) in presence of a metal catalyst to the product of formula (III) and then converting to hydrobromide salt having α-form of formula (I).
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Page/Page column 5
(2011/08/08)
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- SYNTHESIS OF 3--5-[2-(PHENYLSULFONYL)ETHYL]-1H-INDOLE
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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.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ELETRIPTAN AND ITS SALT THEREOF
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The present invention relates to an improved process for the preparation of Eletriptan hydrobromide by hydrolyzing (R)-1-acetyl-5-(2-phenylsulphonylethenyl)-3-(N- methylpyrrolidin-2-ylmethyl)-1 H-indole, followed by reduction in the presence of a metal catalyst, methanesulphonicacid in a solvent, to get the Eletriptan methanesulphonate. Setting free of the methanesulphonate salt with a base and the compound is extracted into an organic solvent, optionally passed the organic layer through silica gel column, the solvent is evaporated to get residue. The residue is dissolved in another solvent followed by addition of aqueous hydrobromic acid to get Eletriptan hydrobromide.
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Page/Page column 19
(2011/02/24)
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- SYNTHESIS OF 3-{[(2R)-1-METHYLPYRROLIDIN-2-YL]METHYL}-5-[2-(PHENYLSULFONYL)ETHYL]-1H-INDOLE
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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.
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Page/Page column 28-30
(2010/11/05)
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- HIGHLY PURE ELETRIPTAN OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF SUBSTANTIALLY FREE OF ELETRIPTAN N-OXIDE IMPURITY
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Provided herein is an impurity of eletriptan, eletriptan N-oxide, (R)-5-[2- (phenylsulfonyl)ethyl]-3 -[(1 -methyl-2-pyrrolidinyl-N-oxide)methyl]- 1H-indole, and a process for the preparation and isolation thereof. Provided further herein is a highly pure eletriptan or a pharmaceutically acceptable salt thereof substantially free of eletriptan N- oxide impurity, processes for the preparation thereof, and pharmaceutical compositions comprising highly pure eletriptan or a pharmaceutically acceptable salt thereof substantially free of eletriptan N-oxide impurity.
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Page/Page column 20
(2010/09/17)
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- NOVEL POLYMORPH OF ELETRIPTAN HYDROBROMIDE AND PROCESS FOR THE PREPARATION THEREOF
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The present invention relates to a novel crystalline polymorphic form D of Eletriptan Hydrobromide characterized by an XRD pattern with two theta values at 18.8., 20.5, 23.7, 24.2. The present invention also relates to a process for making Form D comprising treating Eletriptan in water or in a suitable organic solvent with hydrogen bromide and cooling to temperatures to the range of 10° C or sub-zero temperatures.
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Page/Page column 4
(2010/11/03)
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- NOVEL HEMIOXALATE SALT OF ELETRIPTAN
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The present invention relates to novel hemioxalate salt of eletriptan, process for preparation, pharmaceutical compositions, and method of treating thereof. The present invention relates to solid forms of eletriptan hemioxalate, processes for preparation, pharmaceutical compositions, and method of treating thereof. The solid form of eletriptan hemioxalate is useful for preparing eletriptan free base or a pharmaceutically acceptable salt thereof, particularly eletriptan hydrobromide, in high purity. The present invention also provides a process for preparing substantially pure eletriptan hydrobromide using eletriptan hemioxalate.
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Page/Page column 29-30
(2009/07/18)
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- 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
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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.
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Page/Page column 8
(2009/12/23)
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- Amorphous eletriptan hydrobromide and process for preparing it and other forms of eletriptan hydrobromide
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The invention encompasses amorphous eletriptan hydrobromide, processes for preparing it and pharmaceutical compositions of it. The invention also relates to processes for preparing other forms of eletriptan hydrobromide such as Form α and Form β.
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Page/Page column 10
(2008/12/09)
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- Process
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The present invention provides an improved process for the preparation of α-polymorphic eletriptan hydrobromide.
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- INDOLE DERIVATIVES
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The present invention provides eletriptan hydrobromide monohydrate of the formula (I): together with processes for preparing, uses of, and compositions containing, said monohydrate.
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- Salts of an anti-migraine indole derivative
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PCT No. PCT/EP95/01914 Sec. 371 Date Feb. 2, 1997 Sec. 102(e) Date Feb. 2, 1997 PCT Filed May 17, 1995 PCT Pub. No. WO96/06842 PCT Pub. Date Mar. 7, 1996The present invention relates to hydrobromide salts of 3-(N-methyl-2(R)-pyrrolidinylmethyl)-5-(2-phenylsulphonylethyl)-1H-indole having the formula (I):
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein the substituents are as defined in the description and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of a dihalogenated intermediate.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein n is 0, 1, or 2; X is hydrogen, chlorine, bromine or iodine; R 1 is hydrogen; R 3 is selected from hydrogen and C 1 to C 6 linear or branched alkyl; and R 2 is as defined in the specification and the pharmaceutically acceptable salts thereof are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of a dihalogenated intermediate is also disclosed.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein R 1, R 2, R. sub.3, X and n are as defined in the claims and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting hypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of dihalogenated intermediate is also disclosed.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein R 1, R 2, R. sub.3, X and n are as defined in the claims and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting hypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of dihalogenated intermediate is also disclosed.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein R 1, R 2, R. sub.3, X and n are as defined in the claims and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting hypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of dihalogenated intermediate is also disclosed.
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