- [11C]Olanzapine, radiosynthesis and lipophilicity of a new potential PET 5-HT2 and D2 receptor radioligand
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Olanzapine and its precursor desmethyl-Olanzapine were synthesized from malononitrile, propionaldehyde, 1-fluoro-2-nitrobenzene, and substituted piperazine in 4, 4, 5, and 5 steps with 35%, 32%, 26%, and 32% overall chemical yield, respectively. [11C]Olanzapine was prepared from desmethyl-Olanzapine with [11C]CH3OTf through N-[ 11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [11C]CO 2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB. The calculated Log P (C Log P) value of [11C]Olanzapine is 3.39.
- Gao, Mingzhang,Shi, Zenas,Wang, Min,Zheng, Qi-Huang
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Read Online
- A synthesis of tritium-labeled olanzapine
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A synthesis of olanzapine, 2-methyl-10-(4-methyl-1-piperazinyl)-4H- thieno[2,3-b][1,5]benzodiazepine, was carried out and the conditions for its tritium labeling were optimized to obtain a tritium-labeled olanzapine preparation with a specific radioactivity of 12 Ci/mmol.
- Shevchenko,Nagaev,Kuznetsov,Polunin,Zozulya,Myasoedov
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Read Online
- Direct Reductive Cyclocondensation of the Nitro Group with the Amido Group: Key Role of the Iminophosphorane Intermediate in the Synthesis of 1,4-Dibenzodiazepine Derivatives
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A class of dialkylamino-substituted dibenzodiazepines and their hetero analogues was synthesized by the intramolecular aza-Wittig condensation of the amido group with iminophosphoranes. The one-pot, two-step procedure includes reductive synthesis of the intermediate iminophosphoranes from the corresponding nitroamides and tributylphosphine.
- Tryniszewski, Micha?,Bujok, Robert,Cmoch, Piotr,Gańczarczyk, Roman,Kulszewicz-Bajer, Irena,Wróbel, Zbigniew
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p. 2277 - 2286
(2019/05/16)
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- A method of improving the crystal form II olanzapine and method
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The invention discloses an improved method for preparation of olanzapine. The method comprises the step as follows: in a single solvent, a compound shown in a formula (II) reacts with N-methyl piperazine at the temperature greater than or equal to 111 DEG C. By adopting the method disclosed by the invention, the productivity is about over 85%, and the purity of high performance liquid chromatography is about 99% or about 99.5%, or over about 99.9%. The used solvent and reagent can be recycled, are economical and environment-friendly, and accord with the requirements of green chemistry.
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Paragraph 0050-0051; 0053; 0055
(2018/03/01)
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- Production of [oranzapin[oranzapin]
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PROBLEM TO BE SOLVED: To provide a method for producing an antipsychotic agent, olanzapine, having a desired appearance as a medicine.SOLUTION: A method for producing type II olanzapine is characterized by adding activated clay to an olanzapine solution prepared by dissolving the olanzapine in an organic solvent to purify the olanzapine.
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Paragraph 0025-0028
(2017/10/20)
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- Design and Performance Validation of a Conductively Heated Sealed-Vessel Reactor for Organic Synthesis
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A newly designed robust and safe laboratory scale reactor for syntheses under sealed-vessel conditions at 250 °C maximum temperature and 20 bar maximum pressure is presented. The reactor employs conductive heating of a sealed glass vessel via a stainless steel heating jacket and implements both online temperature and pressure monitoring in addition to magnetic stirring. Reactions are performed in 10 mL borosilicate vials that are sealed with a silicone cap and Teflon septum and allow syntheses to be performed on a 2-6 mL scale. This conductively heated reactor is compared to a standard single-mode sealed-vessel microwave instrument with respect to heating and cooling performance, stirring efficiency, and temperature and pressure control. Importantly, comparison of the reaction outcome for a number of different synthetic transformations performed side by side in the new device and a standard microwave reactor suggest that results obtained using microwave conditions can be readily mimicked in the operationally much simpler and smaller conventionally heated device.
- Obermayer, David,Znidar, Desiree,Glotz, Gabriel,Stadler, Alexander,Dallinger, Doris,Oliver Kappe
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p. 11788 - 11801
(2016/12/09)
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- Method for producing intermediate olanzapine
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PROBLEM TO BE SOLVED: To provide a method for producing an intermediate of olanzapine by a safe and simplified method without using tin chloride.SOLUTION: A method for producing a compound of formula 1 or its acid adduct is characterized by preparing a suspension containing a compound of formula 2, iron powder or zinc powder and a water-soluble alcohol and then adding an acid to the suspension to react them.
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Paragraph 0035
(2020/10/19)
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- Method of manufacturing olanzapine II type
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PROBLEM TO BE SOLVED: To provide a method for obtaining a II type crystal of 2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine (general name:olanzapine) at a high recovery rate, which crystal is useful as an antipsychotic drug.SOLUTION: A method for producing the olanzapine II type crystal comprises the steps of: using water-containing ethyl acetate as a recrystallization solvent when a crude material of the olanzapine is re-crystallized; dissolving the crude material of the olanzapine in the water-containing ethyl acetate; adjusting the amount of the water within 1.5-4.5 moles based on 1 mole of the dissolved olanzapine; precipitating crystals to obtain a new olanzapine hydrate crystal having characteristic peaks at such positions that 2θ is 8.9±0.2°, 9.4±0.2°, 17.1±0.2°, 18.2±0.2°, 18.6±0.2°, 20.2±0.2°, 20.5±0.2°, 20.8±0.2°, 21.7±0.2°, and 26.4±0.2° when X-ray diffraction measurement is performed by using a Cu-Kα ray; and drying the obtained olanzapine hydrate crystal.
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Paragraph 0045-0050
(2018/10/16)
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- Production of [...]
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PROBLEM TO BE SOLVED: To provide olanzapine which is useful as an antipsychotic drug and has high purity.SOLUTION: A method for producing olanzapine comprises the steps of: reacting 4-amino-2-methyl-10H-thieno[2,3-b][1,5]benzodiazepine hydrochloride with N-methylpiperazine in the absence of a solvent at 80-120°C to produce the olanzapine; cooling a reaction mixture obtained at the reaction step to 60-80°C; mixing acetonitrile of, for example, the weight equivalent to 1.18 times of the weight of the 4-amino-2-methyl-10H-thieno[2,3-b][1,5]benzodiazepine hydrochloride, in the cooled reaction mixture; keeping the acetonitrile-mixed reaction mixture at 60-80°C; and adding water of, for example, the weight equivalent to 3 times of the weight of the 4-amino-2-methyl-10H-thieno[2,3-b][1,5]benzodiazepine hydrochloride, to the mixture of 60-80°C to precipitate the olanzapine.
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Paragraph 0040-0056
(2020/10/21)
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- PROCESS FOR THE PREPARATION OF HIGH PURITY OLANZAPINE AND CRYSTALLINE FORM II THEREOF
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The present invention provides a process for the preparation of high-purity olanzapine with high yield and a process for the preparation of olanzapine crystalline Form II, which are industrially applicable. The preparation processes according to the present invention are useful for the preparation of high-purity olanzapine and olanzapine crystalline Form II with high yield and thus can be effectively used for mass production.
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Paragraph 61-65
(2014/10/15)
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- Synthesis and oxidant properties of phase 1 benzepine N-oxides of common antipsychotic drugs
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There is increasing evidence that cell constituents are oxidized by widely used antipsychotic drugs but until now the underlying chemistry has remained unclear. It is well known that such drugs readily undergo N-oxidation as a first key metabolic step. To gain insight into the problem, the tertiary phase 1 N-oxides of clozapine, olanzapine, quetiapine, and zotepine were synthesized, together with the N,S-dioxides of quetiapine and zotepine. These N-oxides were then subjected to well-established chemical transformations to test their oxidant properties in group VIII transition-metal-catalyzed reactions. In the osmium tetroxide catalyzed dihydroxylation of styrene or cinnamyl alcohol and in the tetrapropylammonium perruthenate catalyzed oxidation of cinnamyl alcohol, the benzepine N-oxides could be used as replacements for the standard oxidant, N-methylmorpholine N-oxide (NMO) with varying degrees of efficiency. From a chemical point of view, clozapine N-oxide displayed a comparable oxidation power to NMO, characterizing the benzepines as oxygen carriers. Moreover, quetiapine was found to be an excellent double oxygen acceptor, undergoing initial N-oxidation and subsequent S-oxidation. It is therefore worthwhile considering whether oxidative damage to the human body might be related to the potential redox properties of common antipsychotic drugs. Georg Thieme Verlag Stuttgart ? New York.
- Koerber, Jochen,Loeffler, Stefan,Schollmeyer, Dieter,Nubbemeyer, Udo
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p. 2875 - 2887
(2013/10/22)
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- COMBINATION OF GLYT1 COMPOUND WITH ANTIPSYCHOTICS
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The present invention relates to a pharmaceutical combination of a glycine transporter inhibitor (GlyT1) and an atypical antipsychotic drug which may be used for the treatment of positive and negative symptoms of schizophrenia.
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- PROCESS FOR THE PURIFICATION OF OLANZAPINE
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The present invention relates to a process for the purification of olanzapine, characterized in that said process comprises at least the following steps: (A) providing a solution of olanzapine in at least one organic solvent, (B) treating the solution obtained in step (A) with at least one non-acidic oxide adsorbent, and (C) removing the said non-acidic oxide adsorbent from the solution obtained in step (B), in order to obtain a solution of olanzapine in a pure form, to a mixture comprising olanzapine and at least one addition product of methylene chloride and olanzapine in an amount of 10 to 280 ppm, to a pharmaceutical formulation, to the use of said mixture and to a method of treating mental diseases and conditions, which comprises administering a therapeutically effective amount of said mixture in conjunction with a pharmaceutically acceptable diluent or carrier.
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Page/Page column 17-18
(2011/02/24)
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- Process for the purification of olanzapine
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The present invention relates to a process for the purification of olanzapine, characterized in that said process comprises at least the following steps: (A) providing a solution of olanzapine in at least one organic solvent, (B) treating the solution obtained in step (A) with at least one non-acidic oxide adsorbent, and (C) removing the said non-acidic oxide adsorbent from the solution obtained in step (B), in order to obtain a solution of olanzapine in a pure form, to a mixture comprising olanzapine and at least one addition product of methylene chloride and olanzapine in an amount of 10 to 280 ppm, to a pharmaceutical formulation, to the use of said mixture and to a method of treating mental diseases and conditions, which comprises administering a therapeutically effective amount of said mixture in conjunction with a pharmaceutically acceptable diluent or carrier.
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Page/Page column 11
(2011/04/18)
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- Process For Producing Pure And Stable Form Of 2-Methyl-4-(4-Methyl-1-Piperazinyl) -10H-Thieno[2,3-B] [1,5] Benzodiazepine
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Disclosed is an improved process for producing pure and thermally color stable crystalline Form I of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine and product thereof. The process comprises of reacting 2-(2-aminoanilino)-5-methylthiophene-3-carbonitrile with N-methyl piperazine in conjunction with N-methylpiperazine acid salt, to produce 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine. Also disclosed is a process for obtaining the Polymorphic Form I of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][l,5J benzodiazepine by crystallizing the crude 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine in a mixture of solvents. Further the invention also provides a new polymorph of Olanzapine, dihydrate Form Ji and process for its preparation and a new hydrate Form J2 of Olanzapine having moisture content 1-3% and process for its preparation.
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Page/Page column 4
(2010/12/29)
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- Bifunctional solid catalysts for chemoselective hydrogenation-cyclisation- amination cascade reactions of relevance for the synthesis of pharmaceuticals
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The benzodiazepines olanzapine and clozapine are nowadays manufactured by a three-step process with a final yield below 50%. An approach to environmentally-friendly intensive processes consists in the development of multifunctional solid catalyst able to catalyze multistep reactions. Here, a bifunctional metal-acid solid catalyst has been prepared and is able to carry out hydrogenation-cyclisation-amination reactions in a cascade process. The catalytic system is illustrated for the synthesis of these important antipsychotics, being an alternative for the current industrial process that requires three steps batch reactions, using mineral acids and bases, and stoichiometric amounts of SnCl2.
- Leyva-Pérez, Antonio,Cabrero-Antonino, Jose R.,Corma, Avelino
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scheme or table
p. 8203 - 8209
(2010/11/05)
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- THIENOBENZODIAZEPINE MODULATORS OF D1 RECEPTOR, D2 RECEPTOR, AND/OR 5-HT2 RECEPTOR
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The present invention relates to new thienobenzodiazepine modulators of D1 receptors, D2 receptors, and/or 5-HT2 receptors, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 15
(2010/11/03)
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- Process for Producing Pure Form of 2-Methyl-4-(4-Methyl-1-Piperazinyl)-10H-Thieno[2,3-b] [1,5]Benzodiazepine
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Disclosed is a process for producing pure form of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine. The process comprises of reacting 2-(2-aminoanilino)-5-methylthiophene-3-carbonitrile with N-methyl piperazine in conjunction with N-methylpiperazine acid salt, to produce 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine. Also disclosed is a process for obtaining the Polymorphic Form I of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine by crystallizing the crude 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine in a mixture of solvents.
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Page/Page column 5
(2009/01/24)
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- Process for preparing Olanzapine form I
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An improved for preparing Olanzapine Form I of Formula 1 in the presence of one solvent or a mixture of solvents.
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Page/Page column 2
(2009/05/28)
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- NOVEL PROCESS
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The present invention relates to a novel process for the preparation of pharmaceutically pure olanzapine. The invention is also related to impurities obtained during the preparation of pharmaceutically pure olanzapine and methods for the detection of the impurities.
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Page/Page column 12
(2009/01/20)
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- Processes for the synthesis of olanzapine
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There is provided a process for the preparation of olanzapine comprising: i) reacting 4-amino-2-methyl-10H-thieno-[2,3-b][1,5]benzodiazepine and N-methylpiperazine in a C1 to C4 alcoholic solvent or mixture thereof at suitable temperature and for a suitable time,ii) cooling the reaction mixture, andiii) isolating the precipitated olanzapine.
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Page/Page column 2
(2009/01/24)
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- METHOD FOR PREPARING A MIXED SOLVATE OF 0LANZAPINE
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An improved method is provided for preparing a mixed solvate of olanzapine/water/tetrahydrofuran in a proportion of 1:1:1/2. Said improvement is characterised in that said mixed solvate is basically prepared by means of methylation of the N-desmethylolanzapine with dimethyl sulphate, using tetrahydrofuran and water as solvents.
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Page/Page column 9-10
(2008/06/13)
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- Novel polymorph E of Olanzapine and preparation of anhydrous non-solvated crystalline polymorphic Form I of 2-methyl-4(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine (Olanzapine Form I) from the polymorphic Olanzapine Form E
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The invention provides an Olanzapine pseudopolymoph Form E. The invention provides methods of preparing polymorphic Olanzapine Form E employing rapid crystallization and seeding. The invention provides methods of preparing anhydrous Olanzapine Form I from the Olanzapine Form E by step-wise drying.
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Page/Page column 6
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF OLANZAPINE
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The invention relates to a process for the preparation of 2 -methyl-4 - (4-methylpiperazin- 1-yl) - 10H- thieno- [2 , 3 -b] [1 , 5] benzodiazepine (olanzapine) of the formula (I) by reacting 4-amino-2-methyl-10H-thieno [2,3- b] [1/5] benzodiazepine hydrochloride of the formula (II) with N-methylpiperazine in an organic solvent, which comprises carrying out the reaction in the mixture of toluene and 1, 3-dimethyl-2- imidazolidinone . The invention also encompasses new 2-methyl-4- (4-methylpiperazin-l-yl) -10H-thieno [2,3- b] [1,5] benzodiazepine dihydrochloride trihydrate of the formula (IB) , the preparation thereof and pharmaceutical compositions comprising said new compound.
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Page/Page column 22-23; 23-24; 24-25
(2008/06/13)
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- Process for preparing olanzapine
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A process for preparing olanzapine comprising methylation of N-demethyl olanzapine with a methylating agent in a solvent comprising dichloromethane, methanol, or a mixture thereof.
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Page/Page column 3
(2008/06/13)
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- OLANZAPINE SALTS AND THEIR CONVERSION TO OLANZAPINE FREE BASE
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The present invention provides salts olanzapine useful as intermediates in the isolation of olanzapine from complex reaction mixtures. These salts can be used for the production of olanzapine base which has a suitable purity for pharmaceutical use and can easily be converted to anhydrous olanzapine polymorphic form I, in high yields.
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Page/Page column 25
(2010/02/15)
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- A PROCESS FOR THE PREPARATION OF N-DEMETHYLOLANZAPINE
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The invention relates to the process for the preparation of N- demethylolanzapine and the use of N-demethylolanzapine obtained by the process for the preparation of antipsychotic medicament olanzapine. According to the process of the invention the reaction of an- hydrous piperazine with 4-amino-2-methyl-10H-thieno[2.3-b]- [1.5]benzodiazepine or its inorganic acid addition salt is carried out in molten piperazine, in the absence of a solvent.
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Page/Page column 6; 7
(2008/06/13)
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- MIXED SOLVATE OF OLANZAPINE, METHOD FOR PREPARING IT AND METHOD FOR PREPARING FORM I OF OLANZAPINE THEREFROM
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Said mixed solvate is a solvate of olanzapine/water/tetrahydrofuran in the proportion 1:1:1/2 (I). The method for preparing said solvate comprises treating a crude anhydrous olanzapine with a mixture of tetrahydrofuran/water. The method for preparing Form I of olanzapine includes desolvating the mixed solvate of formula I, by means of drying, in vacuo and under temperature-controlled conditions.
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Page/Page column 11-12
(2010/10/19)
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- A PROCESS FOR PRODUCING PURE FORM OF 2-METHYL-4-(4-METHYL-1-PIPERAZINYL)-10H-THIENO[2,3-b][1,5]BENZODIAZEPINE
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Disclosed is a process for producing pure form of 2-methyl-4-(4-methyl-1-piperazinyl)-10H--thieno[2,3-b][1,5] benzodiazepine. The process comprises of reacting 2-(2-aminoanilino)-5--methylthiophene-3-carbonitrile with N-methyl piperazine in conjunction with N-methylpiperazine acid salt, to produce 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine. Also disclosed is a process for obtaining the Polymorphic Form I of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine by crystallizing the crude 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine in a mixture of solvents.
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Page/Page column 11
(2008/06/13)
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- PROCESS FOR PREPARING CRYSTALLINE FORM I OF OLANZAPINE
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A process for preparing olanzapine Form I comprises: a) cooling a concentrated solution of olanzapine; b) isolating wet crystals of olanzapine Form I; and c) drying wet crystals and recovering olanzapine Form 1. Drying can be conducted by stepwise increases in the drying temperatures, with extended holding times at each temperature condition.
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Page/Page column 10
(2008/06/13)
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- IMPROVED PROCESS FOR MAKING FORM I OF OLANZAPINE.
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This invention discloses a new dihydrate polymorph of Olanzapine (hereinafter referred to as "dihydrate C"), and process for recovering anhydrous Form I of Olanzapine from this novel Dihydrate C.
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Page/Page column 9
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF ANHYDROUS OLANZOPINE HYDROCHLORIDE OF FORM-1
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Malononitrile is reacted with Propionaldehyde in presence of Sulphur Powder and Triethylamine in N,N-dimethlyformamide to give 5-Amino-4-Cyano-2-Methyl Thiophene. 2-fluoronitrobenzene is condensed with 5-Amino-4-Cyano-2-Methyl Thiophene in Isopropyl alcohol and Potassium Hydroxide powder give 4-cyano-2-methyl-1-(2-nitrophenyl amino) Thiophene. Reduction of 4-cyano-2-methyl-1-(2-nitrophenyl amino) Thiophene with Stannous Chloride and Hydrochloric acid in Isopropyl Alcohol and followed by cyclization to get 4-Amino-2-Methyl-10H-Thieno [2,3,-b][1,5] Benzodiazepine . Condensation of 4-amino-2-methyl-10H-Thieno [2,3,-b][1,5] Benzodiazepine and N-methyl Piperazine in presence of Dimethyl Sulfoxide and Toluene gives Olanzapine Technical grade. In anhydrous form. Recrystallization of the Technical grade anhydrous Olanzapine in Dichloromethane gives anhydrous Olanzapine hydrochloride of Form-I.
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Page/Page column 9
(2008/06/13)
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- SYNTHESIS OF 2-METHYL-4-(4-METHYL-1-PIPERAZINYL)-10H-THIENO[2, 3-B][1,5]BENZODIAZEPINE AND SALTS THEREOF
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The invention belongs to the field of organic chemistry and relates to a new process for the purification of olanzapine comprising preparation of acid addition salts of olanzapine and transformation thereof into a pharmaceutically acceptable pure and discoloured final product. The present invention also relates to new processes for the preparation of pure olanzapine.
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Page/Page column 21
(2010/02/14)
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- ISOPROPANOL WATER SOLVATE OF OLANZAPINE
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The invention relates to a novel and well defined Oolvate form of olanzapine which contains 2 molecules of water and 1 molecule of isopropanol per 2 molecules of olanzapine, and which can be converted into other, forms of olanzapine, in particular form (I) of olanzapine, as well as processes for preparing form (I) olanzapine.
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Page/Page column 24
(2010/02/14)
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- A PROCESS FOR MAKING OLANZAPINE IN A POLYMORPH FORM I
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Heating a solid, preferably crystalline, olanzapine acetate can produce olanzapine Form I in high purity, free of other olanzapine forms and in good yields. The olanzapine acetate can also be used to purify raw or technical grade olanzapine and to serve as an intermediary to other forms of olanzapine base.
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Page/Page column 12
(2010/02/13)
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- METHODS OF PREPARING OLANZAPINE
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This invention encompasses methods of synthesizing olanzapine without solvents or by (5) using low boiling organic solvents.
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Page/Page column 6-8; 10-12
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF OLANZAPINE FORM 1 USEFUL AS ANTIPSYCHOTIC DRUG
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This invention provides an improved process for the preparation of Olanzapine Form (I). Olanzapine, which is 2-methyl-4-(4-methyl-l-piperazinyl)-10H-thieno[2,3-b] [1,5] benzodiazapine. More specially, the invention provides insitu improved process for the direct preparation of crystalline form of Olanzapine Form (I). The present invention also provides high pure Olanzapine Form I with single individual impurity less than 0. 1 % by HPLC.
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Page/Page column 8-9; 10-11
(2008/06/13)
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- PROCESS AND INTERMEDIATES FOR THE PREPARATION OF OLANZAPINE
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The invention provides an improved process for preparing Olanzapine as well as intermediates therefor.
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- A PROCESS FOR THE PREPARATION OF A PHARMACEUTICALLY PURE POLYMORPHIC FORM I OF OLANZAPINE
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The present invention relates to a process for the preparation of pharmaceutically pure polymorphic form I of olanzapine, which com-prises crystallization of olanzapine from a solution in methylene chlo-ride, wherein before the crystallization, said solution of olanzapine in methylene chloride is treated with silica gel, preferably at reflux tem-perature. Also disclosed is form I of olanzapine substantially free of im-purity S, as well as a process for removing of impurity S from olanzap-ine polymorphic form I.
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- Process for preparation of hydrates of olanzapine and their conversion into crystalline forms of olanzapine
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The present invention relates to a method for the preparation of hydrates of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno [2,3-b] [1,5] benzodiazepine (hereinafter referred to as Olanzapine). The present invention also relates to a process for conversion of these hydrates into a pure crystalline form of olanzapine referred to as form-I. The present invention also relates to a method of converting Olanzapine Form-2 to Form-1.
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- 2-METHYL-THIENO-BENZODIAZEPINE PROCESS
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The present invention relates to a novel multistep process for preparing thieno-benzodiazepine derivatives having the following structure (I).
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- NOVEL CRYSTAL FORMS OF OLANZAPINE, METHODS FOR THEIR PREPARATION AND METHOD FOR THE PREPARATION OF KNOWN OLANZAPINE CRYSTAL FORMS
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The invention is directed to a series of novel crystalline olanzapine forms, in particular hydrated and solvated crystalline forms of olanzapine, methods of use in pharmaceutical compositions, and method of treating psychiatric disorders using the crystalline forms. One series of the crystalline forms are hydrates, i. e. water containing crystals, wherein water may be present in a ratio of about 2:1.5 to a ratio of about 1:3 olanzapine:water, while another includes solvates such as an isobutanol solvate. The olanzapine crystalline forms include Forms H, G, Y, X, K, S, Q, Z, and J.
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- Crystalline form I of 2-methyl-4-(4-methyl-1-piperazinyl) 10H thieno [2,3-b][1,5]benzodiazepine
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Crystalline Form I of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine characterised by x-ray powder diffraction peaks at approximately 9.94, 8.53, 8.19, 6.86, 6.35, 5.47, 4.83, 4.71, 4.53, 4.22, 4.08, 3.82, 3.75, 3.69, 3.50, 3.34, 3.11, 2.94, 2.82, 2.76, 2.59, 2.34, 2.03, 1.92 d (interplanar spacing) values; infrared absorbance bands at approximately 1456, 1365, 905, 757, 662 and 604 cm?3 and having stable colour at ambient conditions of storage; and the process of its preparation comprising at least two repetitive steps of crystallization from one or more organic solvent by dissolving 2-methyl-4 -(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine in said solvent and allowing crystallization to occur; wherein in at least one step the solution is purified by treating with a solid adsorbent material and filtering; and wherein in the last step the crystalline material is subjected to drying.
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- METHODS FOR PREPARATION OF OLANZAPINE POLYMORPHIC FORM I
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The invention relates to the methods for preparation of olanzapine polymorphic Form I. The invention also relates to the new mixed solvates of olanzapine constituting valuable intermediates used in the preparation of substantially pure olanzapine polymorphic Form I.
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Page/Page column 15-16
(2008/06/13)
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- PROCESS OF PREPARATION OF OLANZAPINE FORM I
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A process for the preparation of polymorph Form I of 2-methyl-4-(4methyl-1-piperazinyl)-10H-thieno(2,3-b)(1,5) benzodiazepine, or olanzapine.
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- Pharmaceutical compositions containing new polymorphic forms of olanzapine and uses thereof
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Pharmaceutical compositions containing Form III, Form IV, Form V olanzapine and/or pharmaceutically acceptable salts thereof. The pharmaceutical compositions are useful for the treatment of psychotic conditions, mild anxiety and gastrointestinal conditions. In particular, the compositions are useful for treating schizophrenia and related disorders, acute mania, Bipolar I Disorder, psychotic mood disorder and psychosis in patients with Alzheimer's disease.
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- Combination treatment for anxiety, depression, obsessive compulsive disorder and psychosis
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The present invention relates to a method of treating depression, obsessive compulsive disorder and psychosis in a mammal, including a human, by administering to the mammal an atypical antipsychotic in combination with an antidepressant agent with improvement in efficiency. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, an atypical antipsychotic, and an SRI.
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- Method for treating depression with olanzapine
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This invention relates to the use of the antipsychotic drug olanzapine for the treatment of depression, including depressive signs and symptoms and Major Depression.
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- METHODS OF TREATMENT USING A THIENO-BENZODIAZEPINE
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2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-[2,3-b][1, 5] benzodiazepine, or an acid salt thereof, has pharmaceutical properties, and is of particular use in the treatment of disorders of the central nervous system. The compound has the following structure: STR1
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- MENTAL DISORDERS
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2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-[2,3-b][1, 5] benzodiazepine, or an acid salt thereof, has pharmaceutical properties, and is of particular use in the treatment of mental disorders. The compound has the following structure: STR1
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