- 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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Read Online
- A Low Rhodium Content Smart Catalyst for Hydrogenation and Hydroformylation Reactions
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Abstract: This paper describes the preparation, broad characterization and study of activity in hydrogenation and hydroformylation reactions of an easily produced 0.18% Rh/Al2O3. Analytical studies on fresh and recycled samples shed light on the smart properties of such catalyst. Results showed high activity as well as fine/excellent chemoselectivity or regioselectivity, characteristics that may suggest a wide range of applicability. Graphic Abstract: The low metal content catalyst 0.18% Rh/Al2O3 was very active in both hydrogenation and hydroformylation reactions so providing intermediates for valuable APIs, as Nabumetone and Eletriptan, and a fragrance with a fresh, green-floral smell, that recalls scent of lily of the valley.[Figure not available: see fulltext.]
- Paganelli, Stefano,Tassini, Riccardo,Rathod, Vikas D.,Onida, Barbara,Fiorilli, Sonia,Piccolo, Oreste
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p. 1508 - 1521
(2020/10/15)
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- A synthesis method according to sets up qu tan hydrobromide
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The invention discloses a synthesis method of eletriptan hydrobromate, which comprises the following steps: reacting (R)-1-acetyl-3-(N-methylpyrrolidinyl-2-methy)-5-bromo-1H-indole and metal in an organic solvent to form a metal complex, reacting the metal complex with a boron reagent in an organic solvent to form aryl borane or aryl borate, carrying out acid-catalyzed hydrolysis to obtain aryl boric acid, and carrying out coupling and hydrolysis on the aryl boric acid and 2-chloroethylphenyl sulfone under the actions of a catalyst and an alkali to obtain eletriptan, or directly carrying out coupling and hydrolysis on the metal complex and 2-chloroethylphenyl sulfone to obtain eletriptan; and carrying out salification on the eletriptan and hydrobromic acid in an organic solvent to finally obtain the eletriptan hydrobromate. The method is simple to operate, has the advantages of high safety, high stability, low cost and higher yield, and is suitable for industrial production.
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Paragraph 0061-0063
(2017/10/22)
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- 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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- A NOVEL PROCESS FOR THE PREPARATION OF ELETRIPTAN
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The present invention relates to a novel process for the preparation of (R)-3-((1-methylpyrrolidin-2-yl)methyl)-5-(2-(phenylsulfonyl)ethyl)-1H-indole and its intermediates thereof.
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Paragraph 0033
(2013/07/25)
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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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Page/Page column 37-38
(2012/02/01)
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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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- Second-generation process research towards eletriptan: A fischer indole approach
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The development of a second-generation process for the synthesis of eletriptan via a Fischer indole cyclisation is described. The finalised process offers several potential advantages over the current route of manufacture including cost, throughput, and safety.
- Ashcroft, Christopher P.,Pettman, Alan,Watkinson, Simon,Hellier, Paul
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experimental part
p. 98 - 103
(2011/09/16)
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- NOVEL PROCESS FOR THE PREPARATION OF ELETRIPTAN
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The present invention relates to a novel process for the preparation of (R)-3-((1-methylpyrrolidin-2-yl)methyl)-5-(2-(phenylsulfonyl)ethyl)-1H-indole and its intermediates thereof.
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Page/Page column 4
(2011/09/16)
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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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Page/Page column 7
(2011/07/29)
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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 19-20
(2010/09/17)
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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 30-31
(2010/11/05)
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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 9
(2009/12/23)
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- MODIFIED FISCHER INDOLE SYNTHESIS OF ELETRIPTAN
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The present invention relates to a new process for the preparation of eletriptan (I), or its enantiomer comprising a modified Fischer indole synthesis, namely the reaction of a compound of formula (II), wherein R1 is a suitable hydrazine protecting group, with a compound of formula (III) wherein R2is an aldehyde group (-CHO) or the functional equivalent thereof.
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Page/Page column 23
(2010/02/14)
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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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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 in the treatment of emesis
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Compounds of formula I, STR1 wherein R1 represents hydrogen; R2 represents hydrogen, halogen, cyano, OR4, --(CH2)m CONR5 R6, --(CH2)m SO2 NR5 R6, --(CH2)m NR7 COR8, --(CH2)m S(O)x R8, --(CH2)m NR7 CONR5 R6, --(CH2)m NR7 COOR9 or --CH=CH(CH2)y R10 ; R3 represents hydrogen or C1-6 alkyl; R4 represents hydrogen, C1-6 alkyl or aryl; R5 and R6 are independently represent hydrogen, C1-6 alkyl, aryl or (C1-3 alkyl)aryl; or R5 and R6 taken together may form a 4-, 5- or 6-membered ring; R7 and R8 independently represent hydrogen, C1-6 alkyl, aryl or (C1-3 alkyl)aryl; R9 represents hydrogen, C1-6 alkyl, aryl or (C1-3 alkyl)aryl; R10 represents --CONR5 R6, --SO2 NR5 R6, --NR7 COR8, --NR7 SO2 R8, --NR7 CONR5 R6, --S(O)x R8 or --NR7 COOR9 ; m is 0, 1, 2 or 3; n is 0, 1 or 2; y is 0, 1 or 2; x is 1 or 2; and pharmaceutically acceptable salts thereof; are useful in the treatment or prevention of emesis not associated with migraine.
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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 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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