- Convenient and industrially viable process for preparation of zolmitriptan
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The present invention provides a convenient and industrially viable process for preparation of zolmitriptan. The invention specifically relates to a method for obtaining (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one hydrochloride of desired purity by separation and isolation in a particular pH range to give higher yield and purity.
- Neelakandan,Manikandan,Santosha,Prabhakaran
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Read Online
- Synthesis of zolmitriptan and related substances
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Efficient and cost-effective synthesis of Zolmitriptan 1 employing Japp-Klingemann reaction and a new robust purification strategy is described.
- Vujjini, Satish Kumar,Mothukuri, Vivekananda Reddy,Islam, Aminul,Bandichhor, Rakeshwar,Kagga, Mukkanti,Malakondaiah, Golla China
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Read Online
- PROCESS FOR PREPARATION OF ZOLMITRIPTAN
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The present invention provides a convenient and industrially viable process for preparation of Zolmitriptan (I) having desired purity. The invention specifically relates to a method for isolating (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one hydrochloride (IIIa) of desired purity by separating the undesired inorganic side products such as stannous hydroxide by manipulation of pH at different stages and finally treating with N,N-dimethylamino butyraldehyde diethyl acetal in an acidic medium to provide Zolmitriptan (I) conforming to regulatory specifications.
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- PROCESS FOR THE PREPARATION OF ZOLMITRIPTAN, SALTS AND SOLVATES THEREOF
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The present invention relates to an improved process for the preparation of the active pharmaceutical ingredient zolmitriptan. In particular, it relates to an efficient process for the preparation of zolmitriptan and its pharmaceutically acceptable salts and solvates.
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Page/Page column 11
(2011/05/16)
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- ORALLY DISINTEGRATING TABLETS OF ZOLMITRIPTAN AND PROCESS FOR PREPARING THE SAME
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Silicon dioxide free orally disintegrating tablet formulations of zolmitriptan or a pharmaceutically acceptable salt thereof having magnesium carbonate heavy and sodium stearyl fumarate with one or more pharmaceutically acceptable excipients and a process for preparing such a formulation and its use in the treatment of migraines.
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- POLYMORPHS OF ZOLMITRIPTAN
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The present invention provides a novel isopropyl acetate solvate form of zolmitriptan, and a process for its preparation thereof. The present invention also provides a process for preparation of zolmitriptan polymorph A. Thus, for example, zolmitriptan isopropanol solvate was dissolved in isopropyl acetate at 25 deg C, the contents were heated to reflux for 30 minutes and the separated solid was filtered, washed with isopropyl acetate to give zolmitriptan isopropyl acetate solvate.
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Page/Page column 4
(2010/07/09)
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- ENANTIOSELECTIVE PROCESS FOR THE PREPARATION OF ZOLMITRIPTAN
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An enantioselective process for preparing zolmitriptan, (S)-4-{[3-[2-(dimethylamine)ethyl]-1H-indol-5-yl]methyl}-2-oxazolidinone), by asymmetric hydrogenation of (Z)-2-(acetylamino)-3-{[3-N,N-(dimethylamine)ethyl)-1H-indol-5-yl]-2-propenoic acid methyl ester in the presence of hydrogen and an enantioselective chiral phosphine transition metal catalyst.
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Page/Page column 8
(2010/09/05)
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- PROCESS FOR THE PREPARATION OF ZOLMITRIPTAN, SALTS AND SOLVATES THEREOF
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The present invention relates to an improved process for the preparation of the activepharmaceutical ingredient zolmitriptan. In particular, it relates to an efficient process for the preparation of zolmitriptan and its pharmaceutically acceptable salts and solvates.
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Page/Page column 17; 22-23
(2009/05/29)
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- A METHOD FOR THE PREPARATION OF ZOLMITRIPTAN
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A method for the preparation of zolmitriptan or its pharmaceutically acceptable salts, comprising isolation of a crystalline salt of zolmitriptan, its optional re-purification and conversion to the substance of formula (III). Zolmitriptan hydrochloride in the crystalline state.
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Page/Page column 5
(2008/12/08)
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- A METHOD FOR THE PREPARATION OF ZOLMITRIPTAN
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In the preparation of zolmitriptan of formula III the reduction of the diazonium salt to (5)-4-(4- hydrazinobenzyl)-l,3-oxazolidin-2-one of formula IV is performed in a more concentrated mixture and by the effect on an alkali metal disulphite, preferably sodium disulphite. A zolmitriptan toluene solvate, characterized by a toluene content of 9 to 14 % by weight according to the gas chromatography determination and by a maximum of the corresponding mass loss at temperatures of about 111°C in the gravimetric analysis record. A zolmitriptan toluene solvate, showing strong Raman bands at the wave numbers of 1443 and 1354 cm-1, characteristic for the crystal lattice of zolmitriptan with built-in toluene, and further marked bands at 1004 and 786 cm-1, characteristic for toluene.
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Page/Page column title page; 5-7
(2008/12/08)
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- AN IMPROVED PROCESS FOR PURIFICATION OF ZOLMITRIPTAN
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The present invention relates to an improved and novel process for the purification of the Zolmitriptan (I) to get highly pure drug substance of greater than 99.8% purity. Zolmitriptan is a 5HT1-like receptor agonist useful in the treatment and prophylaxis of migraine and is chemically known as (S)-4-[(3-[2-(Dimethylamino) ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone (I). A novel method of purification of the drug substance Zolmitriptan (I) is developed and is described.
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Page/Page column 6
(2010/11/29)
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- Process for preparing optically pure zolmitriptan
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A process for preparing zolmitriptan, proceeding through the intermediate Ethyl-3-[2-(1,3-dioxo-2,3-dihydro-1H-2-isoindoleyl)ethyl]-5-[(4S)-2-oxo-1,3-oxazolan-4-ylmethyl]-1H-2-indole carboxylate.
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Page/Page column title page; 9-10; Figure 1
(2010/02/14)
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- PROCESS FOR PREPARING ZOLMITRIPTAN COMPOUNDS
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In particular, zolmitriptan or a pharmaceutically acceptable salt thereof, which includes a) Preparation of the diazonium salt of the aniline hydrochloride (II); followed by reduction and acidification to give hydrazine (III); b) In situ Reaction of the hydrazine hydrochloride (III) with ?-keto-?-valerolactone, to give the hydrazone (IV); c) Fischer indole synthesis of the hydrazone (IV), to give the pyranoindolone of formula (V); d) Transesterification of the pyranoindolone (V) to provide the compound (VI), in which R means a straight or branched C1-C4 alkyl; e) Conversion of the hydroxyl group of the compound (VI) into dimethylamino to give the indolecarboxylate (VII), in which R means a straight or branched C1-C4 alkyl; f) Saponification of the 2-carboalkoxy group of the compound (VII), to provide indolecarboxylic acid (VIII); g) Decarboxylation of the indolecarboxylic acid (VIII), to provide zolmitriptan and, eventually, to provide a pharmaceutically acceptable salt thereof.
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- A process for the purification of (S)-4-((3-(dimethylamino)ethyl)-1H-indol-5yl)-methyl)-2-oxazolidinone
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A process for the purification of (S)-4-{[3-(dimethylamino)ethyl]-1H-indol-5yl]-methyl}-2-oxazolidinone and non-solvated, pure (S)-4-{[3-(dimethylamino) ethyl]-1H-indol-5y1]-methyl}-2-oxazolidinone.
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- One pot synthesis of 2-oxazolidinone derivatives
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PCT No. PCT/GB96/01885 Sec. 371 Date May 13, 1998 Sec. 102(e) Date May 13, 1998 PCT Filed Aug. 2, 1996 PCT Pub. No. WO97/06162 PCT Pub. Date Feb. 20, 1997The present invention provides an improved process for preparing (S)-4-{[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl}-2-oxazolidinone which comprises: a) forming a carbamate of formula (III), from methyl 4-nitro-(L)-phenylalaninate hydrochloride; b) reducing the compound of formula (III) to give the compound of formula (IV); c) reducing the methyl ester grouping in the compound of formula (IV) to give the compound of formula (V); d) ring closure of the compound of formula (V) to give the compound of formula (VI); e) diazonium salt formation from the compound of formula (VI) followed by reduction to give the compound of formula (VII); f) Fischer reaction of the compound of formula (VII) to give (S)-4-{[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl}-2-oxazolidinone.
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- Computer-Aided Design and Synthesis of 5-Substituted Tryptamines and Their Pharmacology at the 5-HT1D Receptor: Discovery of Compounds with Potential Anti-Migraine Properties
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The design and synthesis of a series of novel 5-substituted tryptamines with pharmacological activity at 5-HT1D and other monoamine receptors is described.Structural modifications of N- and C-linked (prinicipally hydantoin) analogues at the 5-position were synthesized and their pharmacological activities were utilized to deduce significant steric and electrostatic requirements of the 5-HT1D and 5-HT2A receptor subtypes.Conformations of the active molecules were computed which, when overlaid, suggested a pharmacophore hypothesis which was consistent with the affinity and selectivity measured at 5-HT1D and 5-HT2A receptors.This pharmacophore is composed of a protonated amine site, an aromatic site, a hydrophobic pocket, and two hydrogen-bonding sites.A 'selectively site' was also identified which, if occupied, induced selectivity for 5-HT1D over 5-HT2A in this series of molecules.The development and use of the pharmacophore models in compound design is described.In addition, the physicochemical constraints of molecular size and hydrophobicity required for efficient oral absorption are discussed.Utilizing the pharmacophore model in conjuction with the physicochemical constraints of molecular size and log DpH7.4 led to the discovery of 311C90 (6), a new selective 5-HT1D agonist with good oral absorption and potential use in the treatment of migraine.
- Glen, Robert C.,Martin, Graeme R.,Hill, Alan P.,Hyde, Richard M.,Woollard, Patrick M.,et al.
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p. 3566 - 3580
(2007/10/03)
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- Indolyl tetrahydropyridines for treating migraine
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STR1 The present invention is concerned with compounds of formula (I), wherein n is an integer of from 0 to 3: W is a group of formula (i), (ii), or (iii), wherein R is hydrogen or C1-4 alkyl, X is --O--, --S--, --NH--, or --CH2 --, Y is oxygen or sulphur and the chiral center (*) in formula (i) or (ii) is in its (S) or (R) form or is a mixture thereof in any proportions: and Z is a group of formula (iv), (v), or (vi), wherein R1 and R2 are independently selected from hydrogen and C1-4 alkyl and R3 is hydrogen or C1-4 alkyl; and their salts, solvates and physiologically functional derivatives, with processes for their preparation, with medicaments containing them and with their use as therapeutic agents, particularly in the prophylaxis and treatment of migraine.
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