- Isotope-Edited Infrared Spectroscopy for Efficient Discrimination between Pharmaceutical Salts and Cocrystals
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Isotope-edited infrared spectroscopy using carboxylic acids selectively labeled with 13C is proposed herein for the efficient discrimination of pharmaceutical salts and cocrystals, whereby proton-transfer probe vibrations are highlighted by isotope shifts. This new technique can accurately discriminate even a confusing salt from a cocrystal for the traditional method, highlighting the diagnostic peaks. In addition, the established technique also provided the OH in-plane bending vibrations corresponding to intermolecular hydrogen bonding at the carbonyl oxygens of the cocrystals. The technique will accelerate the discrimination, which is a critical process in cocrystal development.
- Iwata, Kentaro,Karashima, Masatoshi,Ikeda, Yukihiro
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p. 2350 - 2358
(2017/07/12)
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- Method for preparing the advantage grips Qu Tan a benzoic acid
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The invention discloses a novel preparation method for rizatriptan benzoate. The preparation method uses indoline as a starting material, and performs five-step reaction of triazole methylation, dehydrogenation, side chain formation, reduction and salt formation so as to obtain the rizatriptan benzoate. The innovative point of the method is that a brand-new method for forming an indole ring is adopted, and the defects caused by a fisher indole synthesis method adopted in a conventional course that the impurity content of the product is high, and the purification is difficult. The method has the advantages that the operation is simple and convenient, the reaction condition is mild, no expensive reagent is used, and the product purity is high.
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- the advantage grips Qu Tan a method of preparing benzoic acid
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The invention discloses a novel method for preparing rizatriptan benzoate. According to the method, high-purity rizatriptan benzoate is prepared by performing seven steps of reaction of N,N-methylation, reduction, protection, triazole methylation, deprotection, dehydrogenation and salifying on tryptamine as an initial raw material. The method is characterized in that indole rings are established by using a novel method, and the defects that the product impurity content is high and purification is difficult because of a fisher indole synthesis method used in the conventional process are avoided. The method has the advantages that the operation is simple and convenient, the reaction condition is gentle, no expensive reagents is used, column chromatography purification is not needed, and the product purity is high.
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- NOVEL PROCESS
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The present invention relates to a novel process for the preparation of rizatriptan and its pharmaceutically acceptable salts. It provides a novel process for the preparation of highly pure rizatriptan, which can be easily adopted for commercial production with a high degree of consistency in purity and yield. Subsequently the rizatriptan base prepared can be converted into any suitable pharmaceutically acceptable salt, such as the oxalate, succinate or benzoate salt, for dosage form preparation. The present invention also provides a composition comprising rizatriptan useful for the manufacture of a medicament for the treatment or prevention of migraine.
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Page/Page column 7
(2010/10/19)
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- NOVEL PROCESS
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The present invention relates to a novel process for the preparation of rizatriptan and its pharmaceutically acceptable salts. It provides a novel process for the preparation of highly pure rizatriptan, which can be easily adopted for commercial production with a high degree of consistency in purity and yield. Subsequently the rizatriptan base preparedcan be converted into any suitable pharmaceutically acceptable salt, such as the oxalate, succinate or benzoate salt,for dosage form preparation. The present invention also provides a composition comprising rizatriptan useful for the manufacture of a medicament for the treatment or prevention of migraine.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF RIZATRIPTAN
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The present invention relates to an improved process for preparing N,N-dimethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indole-3-ethanamine of Formula I and its pharmaceutically acceptable salts.
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Page/Page column 11-12
(2008/12/06)
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- PROCESS FOR THE LARGE SCALE PRODUCTION OF RIZATRIPTAN BENZOATE
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The present invention provides a method for preparing pure Rizatriptan benzoate having purity more than 99.5% and dimer impurity less than 0.1% comprises, i) Condensation of 1,2,4-Triazole with 4-Nitro benzyl bromide to yield l-(4-nitrophenyl) methyl-1,2,4- triazole ii) Reducing the l-(4-nitrophenyl) methyl-1,2,4-triazole to give l-(4- aminophenyl) methyl-1,2,4-triazole iii) Converting l-(4-aminophenyl) methyl-1,2,4-triazole to l-(4-hydrazinophenyl) methyl-1,2,4-triazole hydrochloride iv) Condensing the hydrazine derivative with 4-(Dimethylamino) butanal diethylacetal to get Rizatriptan and v) Salification of Rizatriptan to Rizatriptan benzoate.
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Page/Page column 9-10
(2008/06/13)
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- Amorphous rizatriptan benzoate
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Rizatriptan benzoate in an amorphous form is disclosed. Also disclosed is a process for preparing rizatriptan benzoate substantially in amorphous form comprising the steps of (a) preparing a solvent solution comprising non-amorphous rizatriptan benzoate a
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Page/Page column 4-5
(2008/06/13)
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- IMPROVED PROCESS FOR THE PREPARATION OF RIZATRIPTAN BENZOATE
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Present invention discloses an improved and commercially viable process for the preparation of rizatriptan benzoate of formula (I). According to the present process the hydrazone intermediate derived from the phenylhydrazine of formula- (III) and 4- dimethylaminobutyraldehyde diethyl acetal is gradually heated to 60-70 °C in aqueous sulfuric acid medium and maintained for 3-4hr to get rizatriptan with less dimeric impurity of formula (X). The resultant rizatriptan is isolated and converted into the pharmaceutically acceptable benzoate salt. Present process produces less percentage of dimeric (less than 3 %) or polymeric impurities compared to the prior art process and more yield of rizatriptan. Rizatriptan benzoate produced according to the present process has more than 99.5 % purity with less than 0.1% dimeric impurity of formula (X) by HPLC. Rizatriptan benzoate is useful for the treatment of migraine.
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- NOVEL CRYSTALLINE FORMS OF RIZATRIPTAN BENZOATE
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Present invention relates to three novel crystalline forms, named as Form I, II, and III of rizatriptan benzoate, process for their preparation and pharmaceutical compositions containing them.
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Page/Page column 4
(2008/06/13)
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- RIZATRIPTAN PROCESS
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Rizatriptan is prepared by reacting 4-hydrazinophenylmethyl-1,2,4-triazole dihydrochloride with 4-N,N-dimethylaminobutanal dimethylacetal in the presence of hydrochloric acid.
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Page/Page column 11
(2008/06/13)
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- SYNTHESIS METHODS AND INTERMEDIATES FOR THE MANUFACTURE OF RIZATRIPTAN
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The invention relates to a process for the manufacture of an 1,2,4-triazol-1-yl compound of the formula [A], or a salt thereof, wherein each of R3 and R4 is hydrogen or lower alkyl, said process comprising reacting a hydrazine compound of the formula [B] wherein R is hydrogen or acyl, R2 is hydrogen or a protecting group, are hydrogen or lower alkyl, and R6 is hydrogen or COOR7, or a salt thereof, with a 1,2,4-triazolyl forming reagent. In addition, novel intermediates for the synthesis of the anti-migraine agent Rizatriptan and methods for their synthesis are presented.
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Page/Page column 51
(2010/02/13)
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- PROCESS FOR PREPARING RIZATRIPTAN
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In particular, rizatriptan 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 the hydrazine (III); b) reaction in situ of the hydrazine hydrochloride (III) with α-keto-δ-valerolactone, to give the hydrazone (IV); c) Fischer indole reaction of the hydrazone (IV), to give the pyranoindolone (V), optionally followed by a hydrolysis reaction to give (VI); d) Transesterification of (V) or esterification of its hydrolysis product (VI), to give (VII), where R means straight or branched C1-C4 alkyl chain; e) Conversion of the hydroxyl group of (VII) into dimethylamino, to give the indolecarboxylate (VIII), where R has the meaning defined above; f) Saponification of the 2-carboalkoxy group of (VIII) to give indolecarboxylic acid (IX); and g) Decarboxylation of the indolecarboxylic acid (IX) to give rizatriptan and, eventually, to obtain a pharmaceutically acceptable salt thereof. The invention also relates to synthesis intermediates to obtain rizatriptan.
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- Synthesis of the 5-HT1D receptor agonist MK-0462 via a Pd-catalyzed coupling reaction
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Application of a palladium-catalyzed coupling between 3 and 5a to the synthesis of the novel 5-HT1D receptor agonist MK-0462 (1), a potential anti-migraine drug, is described.
- Chen, Cheng-Yi,Lieberman, David R.,Larsen, Robert D.,Reamer, Robert A.,Verhoeven, Thomas R.,Reider, Paul J.,Cottrell, Ian F.,Houghton, Peter G.
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p. 6981 - 6984
(2007/10/02)
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