- Pyrophosphoryl Chloride: A Green, Reductive Chlorination Reagent Utilized in the One-Pot Synthesis of Quetiapine
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A one-pot synthesis of quetiapine from dibenzo[b,f][1,4]thiazepin-11(10H)-one and 4-hydroxyethoxy ethyl piperazine (HEEP) in toluene using N,N-dimethylaniline (DMA) and pyrophosphoryl chloride (P2O3Cl4) as a green reductive chlorination agent is described. A significant shortening of reaction times, a nearly quantitative yield, and high atom economy in the product were observed. The simplicity of the reaction, ease of execution, simple workup, and good yields, together with the use of easily accessible starting materials and an environmentally friendly procedure, are hallmarks of this process.
- Mahmoodi,Pourhossein Parizad,Hosseini
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Read Online
- 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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Read Online
- Crystallographic evaluation of the conformation of quetiapine included in β-cyclodextrin
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Single-crystal X-ray diffraction and theoretical calculations were conducted for insights into the β-cyclodextrin (β-CD)-quetiapine inclusion complex structure. β-CD and quetiapine form a host–guest inclusion complex at a ratio of 2:1 in which the β-CD molecules form head-to-head dimers with their secondary hydroxyl groups linked by multiple hydrogen bonds. Quetiapine is totally contained within the β-CD cavity and exhibits two kinds of disorder (parts 1 and 2) in opposite directions in the β-CD complex. To clarify the mobility of the guest molecule in the β-CD cavity, theoretical molecular conformational calculations, crystal optimization and crystal energy calculations were conducted using CONFLEX software. The results of theoretical molecular conformation calculations showed that the mobility of quetiapine is restricted because its tricyclic structure is covered by β-CD. The results of crystal energy calculations indicated that the conformation of disorder part 1, which has high occupancy, was more stable.
- Endo, Tomohiro,Ishihara, Shintaro,Kaga, Mayumi,Kawashima, Yoshiaki,Matsumoto, Takashi,Nagase, Hiromasa,Ogawa, Noriko,Ueda, Haruhisa,Yamamoto, Hiromitsu,Yasunaga, Toshiya
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Read Online
- Cobalt-Catalyzed Direct C-H Thiolation of Aromatic Amides with Disulfides: Application to the Synthesis of Quetiapine
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A direct C(sp2)-H thiolation of aromatic amides with disulfides was developed. The coupling reaction proceeds between the thioether radical and cobaltacycle intermediate. This method exhibits a relatively broad substrate scope and high functional group compatibility. A mechanistic study indicates that the cobalt(IV) intermediate is probably formed during the course of the reaction. The thiolation product can be transformed to Quetiapine, which is an atypical antipsychotic agent approved for the treatment of schizophrenia and bipolar disorder.
- Li, Mingliang,Wang, Jun Joelle
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Read Online
- Synthesis of PEG-Functionalized Amines Using Ruthenium-Catalyzed Hydrogen Borrowing
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The polyethylene glycol (PEG) moiety has become increasingly important in medicinal chemistry. Herein, we describe the PEG functionalization of amines via hydrogen borrowing reductive amination. This was accomplished using the [Ru(p-cymene)Cl2]2 catalyst and phosphorus-containing ligand dppf or DPE to yield a variety of PEGylated primary and secondary amine products. Furthermore, we illustrate the utility of this method with the synthesis of quetiapine (Seroquel) in 62percent isolated yield.
- Rossi, Federico V.,Starr, Jeremy T.,Uccello, Daniel P.,Young, Jennifer A.
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Read Online
- Synthesis method of quetiapine
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The invention discloses a method for preparing quetiapine, which comprises the following steps: taking 11-chlorodibenzo [b, f] [1, 4] thiazoline, 1, 4-diazabicyclo [2.2. 2] octane and 2-(tert-butyldimethylsilyl) oxy) ethanol as reaction raw materials to obtain an intermediate, and finally hydrolyzing under an acidic condition to obtain quetiapine. The problem that heavy metal exceeds the standard does not need to be considered in the post-treatment process; the generated impurities are relatively reduced, the environmental pollution is less, the method just conforms to the currently advocated green synthesis, and the environment-friendly development of the synthesis production and the environment is embodied.
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Paragraph 0070-0072
(2022/04/06)
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- Preparation method of quetiapine
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The invention discloses a method for synthesizing quetiapine by using a ruthenium catalyst. 11-[4-[2-(2-hydroxyethoxy) ethyl-1-piperazinyl]]-dibenzo [b, f] [1, 4] sulfur nitrogen is prepared from 11-piperazinyl dibenzo [b, f] [1, 4] sulfur nitrogen and diethylene glycol as raw materials under the catalytic action of a ruthenium catalyst, the product purity is greater than or equal to 95%, and the yield is greater than or equal to 90%. The method has the advantages of mild reaction conditions, high atom utilization rate, high product yield, low cost and environmental friendliness, and is suitable for industrial production, and water is the only by-product.
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Paragraph 0011; 0016; 0022-0031
(2021/06/13)
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- Direct: N -alkylation of sulfur-containing amines
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An efficient ruthenium-catalyzed method has been developed for the direct N-alkylation of sulfur-containing amines with alcohols, for the first time, by a step-economical and environmentally friendly hydrogen borrowing strategy. The present methodology features base-free conditions and broad substrate scope, with water being the only by-product. Moreover, this protocol has been applied to the synthesis of the pharmaceutical drug Quetiapine.
- Li, Chen,Ge, Min-Tong,Bai, Liang,Xia, Ai-Bao,Xu, Dan-Qian,Xu, Zhen-Yuan
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supporting information
p. 4478 - 4482
(2021/05/31)
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- Nickel-Catalyzed Amination of (Hetero)aryl Halides Facilitated by a Catalytic Pyridinium Additive
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An efficient and operationally simple Ni-catalyzed amination protocol has been developed. This methodology features a simple NiII salt, an organic base and catalytic amounts of both a pyridinium additive and Zn metal. A diverse number of (hetero)aryl halides were coupled successfully with primary and secondary alkyl amines, and anilines in good to excellent yields. Similarly, benzophenone imine gave the corresponding N-arylation product in an excellent yield.
- Han, Dongyang,Li, Sasa,Xia, Siqi,Su, Mincong,Jin, Jian
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supporting information
p. 12349 - 12354
(2020/09/09)
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- Quetiapine artificial hapten, artificial antigen and preparation method and application thereof
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The invention discloses a quetiapine artificial hapten, an artificial antigen as well as a preparation method and application thereof. The molecular structural formula of the quetiapine artificial hapten is shown as a formula (I), and the molecular structural formula of the quetiapine artificial antigen is shown as a formula (II). According to the quetiapine artificial hapten, the characteristic structure of quetiapine is reserved to the maximum extent, and the quetiapine artificial hapten has an active group capable of being coupled with carrier protein and can be used as an antigen determinant; the further prepared quetiapine artificial antigen can be immunized to obtain an anti-quetiapine antibody with high affinity, high sensitivity and strong specificity, the titer of immune ascites obtained by immunizing Balb/c mice reaches up to 1: 78000, and the quetiapine artificial antigen can be used for rapid and accurate immunodetection and immunoassay of quetiapine.
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Paragraph 0048-0052; 0065-0069
(2020/11/01)
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- Generation of Aryl Radicals from Aryl Halides: Rongalite-Promoted Transition-Metal-Free Arylation
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A new and practical method for the generation of aryl radicals from aryl halides is reported. Rongalite as a novel precursor of super electron donors was used to initiate a series of electron-catalyzed reactions under mild conditions. These transition-metal-free radical chain reactions enable the efficient formation of C-C, C-S, and C-P bonds through homolytic aromatic substitution or SRN1 reactions. Moreover, the synthesis of antipsychotic drug Quetiapine was performed on gram scale through the described method. This protocol demonstrated its potential as a promising arylation method in organic synthesis.
- Yu, Fazhi,Mao, Runyu,Yu, Mingcheng,Gu, Xianfeng,Wang, Yonghui
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p. 9946 - 9956
(2019/09/04)
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- New method for preparing quetiapine
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The invention provides an efficient and concise method for preparing highly-pure 1-[2-(2-hydroxyethoxy)ethyl]piperazine hydrochloride, and a method for preparing quetiapine through directly reacting 11-chloro-dibenzo[b,f][(1,4)]thiazepine with 1-[2-(2-hydroxyethoxy)ethyl]piperazine hydrochloride which substitutes the free alkali form. A low-temperature recrystallization technology adopted to purify the 1-[2-(2-hydroxyethoxy)ethyl]piperazine hydrochloride avoids the residual of unknown tiny piperazine impurities in the product during high-temperature purification, so the highly-pure quetiapineis obtained in subsequent reactions.
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Paragraph 0030-0031
(2018/04/21)
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- A [...] synthesis process (by machine translation)
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The present invention discloses a process for synthesizing [...], comprises the following steps: compound of formula (II), C1 - C4 acid mixed, and heated to 80 - 100 °C, adding zinc powder or iron powder, thermal insulation reaction 4 - 6h, shall quetiapine; with the resulting quetiapine fumaric acid salifying, [...], wherein quetiapine with fumaric acid feeding molar ratio of 1: 0.5. The process of the invention has simple operation, high yield, the resulting high purity of the product advantages, and is easy to realize industrial. (by machine translation)
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- Quetiapine synthesizing method
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The invention discloses a quetiapine synthesizing method. O-chlorobenzoic acid with the low price is adopted as a starting material to react with thiophenol, and then ring closure is performed to obtain thioxanthone. Hydroxyl amination and Beckmann rearrangement are performed to obtain a key intermediate dibenzo[b,f][1,4]thiazepines-11-(10H)one, chlorination is performed, then, a reaction is performed on 1-(2-hydroxyethoxy)ethylpiperazine with the existence of acid-binding agent to obtain quetiapine, and the quetiapine and fumaric acid form a salt in an absolute ethyl alcohol system to obtain a product. According to the quetiapine synthesizing method, raw materials are low in price and easy to obtain, the steps are simple, operation is easy, and the cost can be effectively lowered. According to the method, the high-purity quetiapine can be obtained, the liquid phase purity of the obtained semi-fumaric acid quetiapine obtained through salt forming is 99% or above, and the quetiapine synthesizing method can be applied to the field of medicine.
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Paragraph 0080; 0081
(2017/06/27)
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- PROCESS FOR THE SYNTHESIS OF QUETIAPINE
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The present invention relates to a process for the synthesis of quetiapine. In particular, a process is provided for the synthesis of quetiapine of formula (A) comprising reacting dibenzo[b,f][1,4]thiazepin-11(10H)-one, intermediate (I) with phosphorous oxychloride to give 11-chlorodibenzo[b,f][1,4]thiazepine, intermediate (II) wherein the said reaction of intermediate (I) to intermediate (II) is performed in an organic solvent in the presence of a mixture of an organic base together with an inorganic base.
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Page/Page column 2-3
(2011/06/10)
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- A PROCESS FOR PREPARING QUETIAPINE FUMARATE
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The present invention relates to a process for preparing Quetiapine fumarate of formula (I)
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Page/Page column 7-9
(2010/04/06)
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- PROCESS FOR THE SYNTHESIS OF QUETIAPINE
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The present invention relates to a process for the synthesis of quetiapine. In particular, a process is provided for the synthesis of quetiapine of formula (A) comprising reacting dibenzo [b, f ] [1, 4] thiazepin- 11 (10H) -one, intermediate (I) with phosphorous oxychloride to give 11- chlorodibenzo [b, f ] [1, 4] thiazepine, intermediate (II) wherein the said reaction of intermediate (I) to intermediate (II) is performed in an organic solvent in the presence of a mixture of an organic base together with an inorganic base.
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Page/Page column 9-10
(2010/08/09)
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- A PROCESS FOR PREPARING QUETIAPINE FUMARATE
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The present invention relates to an improved process for preparing Quetiapine fumarate of formula (I).
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Page/Page column 11
(2010/08/05)
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- DIBENZOTHIAZEPINE MODULATORS OF DOPAMINE, ALPHA ADRENERGIC, AND SEROTONIN RECEPTORS
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The present invention relates to new dibenzothiazepine modulators of D1 receptors, D2 receptors, alpha-1 adrenergic receptors, alpha-2 adrenergic receptors, H1 receptors, 5-HT1A receptors, and/or 5-HT2 receptors, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 28
(2010/04/23)
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- PROCESS FOR PREPARING QUETIAPINE AND QUETIAPINE FUMARATE
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The invention comprises a process for preparing quetiapine and/or its salts, including, quetiapine fumarate. The process generally comprises reacting dibenzothiazepinone (dibenzo[bf][1,4]thiazepin-11(10H)-one) with phosphorous oxychloride in the presence of triethylamine in an aromatic organic solvent such as toluene or, preferably, xylene at reflux temperature to obtain an aromatic hydrocarbon solution of 11-chloro-dibenzo[bf][1,4]thiazepine. Thereafter, the 11-chloro-dibenzo[bf][1,4]thiazepine is reacted with 2-(2-piperazin-1-ylethoxy)-ethanol to yield, following several processing steps, quetiapine. Compound I can then be further reacted with fumaric acid at elevated temperature to yield quetiapine fumarate. The resulting quetiapine fumarate obtained is suitable for use in pharmaceutical preparations.
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Page/Page column 3; 7-9
(2009/04/24)
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- A PROCESS FOR THE PREPARATION OF QUETIAPINE
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The invention relates to a method for the preparation of 11- (4- [2- (2- hydroxyethoxy) ethyl] -1-piperazinyl] dibenzo [b, f ] -1, 4-thiazepine and pharmaceutically acceptable salts thereof comprising the reaction of 1- [2- (hydroxyethoxy) -ethyl] piperazine with dibenzo [b, f] [1, 4] thiazepin-11-ylamine.
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Page/Page column 10
(2009/09/05)
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- Process for preparing quetiapine fumarate
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Provided is an improved synthesis of quetiapine and pharmaceutically acceptable salts.
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- IMPROVED PROCESS FOR PREPARING QUETIAPINE FUMARATE
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Provided is an improved of quetiapine and pharmaceutically acceptable salts.
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Page/Page column 13; 28-29
(2008/12/04)
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- Identification, isolation, synthesis and characterization of impurities of quetiapine fumarate
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In the process for the preparation of quetiapine fumarate (1), six unknown impurities and one known impurity (intermediate) were identified ranging from 0.05-0.15% by reverse-phase HPLC. These impurities were isolated from crude samples using reverse-phase preparative HPLC. Based on the spectral data, the impurities were characterized as 2-[4-dibenzo[b,f][1,4]thiazepine-11-yl-1- piperazinyl]1-2-ethanol (impurity I, desethanol quetiapine), 11-[(N-formyl)-1-piperazinyl]-dibenzo[b,f][1,4]thiazepine (impurity II, N-formyl piperazinyl thiazepine), 2-(2-hydroxy ethoxy)ethyl-2-[2-[4-dibenzo[b,f][1,4] thiazepine-11-piperazinyl-1-carboxylate (impurity III, quetiapine carboxylate), 11-[4-ethyl-1-piperazinyl]dibenzo [b,f][1,4] thiazepine (impurity IV, ethylpiperazinyl thiazepine), 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1- piperazinyl)ethoxy]1-ethyl ethanol [impurity V, ethyl quetiapine), 1,4-bis[dibenzo[b,f][1,4]thiazepine-11-yl] piperazine [impurity VI, bis(dibenzo)piperazine]. The known impurity was an intermediate, 11-piperazinyl-dibenzo [b,f][1,4]thiazepine (piperazinyl thiazepine). The structures were established unambiguously by independent synthesis and co-injection in HPLC to confirm the retention times. To the best of our knowledge, these impurities have not been reported before. Structural elucidation of all impurities by spectral data (1H NMR, 13C NMR, MS and IR), synthesis and formation of these impurities are discussed in detail.
- Bharathi,Prabahar,Prasad,Srinivasa Rao,Trinadhachary,Handa,Dandala, Ramesh,Naidu
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- PROCESSES FOR THE PREPARATION OF THIAZEPINES
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The present invention relates to new processes for the preparation of thiazepines and of salts thereof. Specifically the present invention provides simple one-pot processes for the preparation of thiazepines. The invention further relates to the use of essentially the same inert solvent or of a mixture of inert solvents for the preparation of thiazepines and salts thereof, to the use of an about equimolar amount of a starting material and a halogenating agent for the preparation of thiazepines and to compositions useful in the process of the invention.
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Page/Page column 14; 16
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF AN 11-(4-SUBSTITUTED-I-PIPERAZINYL)DIBENZO[b,f][1,4]THIAZEPINE DERIVATIVE
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A process for the preparation of an 11-(4-substituted-1-piperazinyl)dibenzo[b,f][1,4]thiazepine derivative, of general Formula (I), where A is hydrogen or a -(CH2)2-OH group or a -(CH2)2-0-(CH2)2-OH group, or of a salt thereof, comprises a step in which 10H-dibenzo[b,f][1,4]thiazepin-11-one is reacted with a piperazine derivative in the presence of a titanium alkoxide of general formula Ti(OR)4, where R is a straight or branched alkyl group, having from one to eight carbon atoms to obtain said Formula I derivative or a salt thereof. Where A is -(CH2)2-0-(CH2)2-OH, then the piperazine derivative is 1-(2-(2-hydroxyethoxy)ethyl)piperazine and the 11-(4-substituted-1-piperazinyl)dibenzo[b,f][1,4]thiazepine is quetiapine, (11-(4-(2-(2-hydroxyethoxy)ethyl)-1-piperazinyl)dibenzo[b,f][1,4]thiazepine). The process may comprise an additional step of reacting the quetiapine with fumaric acid to obtain quetiapine hemifumarate.
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Page/Page column 12-15
(2008/06/13)
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- PROCESS FOR PRODUCING 11-[4-[2-(2-HYDROXYETHOXY)ETHYL]-1-PIPERAZINYL]DIBENZO[b,f][1,4]THIAZEPINE AND A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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A process for producing 11-[4-[2-(2-hydroxyethoxy)ethyl]-l-piperazinyl]dibenzo [b,f][1,4]thiazepine [I] and a pharmaceutically suitable acid addition salt is disclosed. Accordingly, thiosalicylic acid [XVI] is reacted with o-halonitrobenzene [XVII] using a phase transfer catalyst to obtain 2-nitro-2'-carboxydiphenylsulphide [XI]. It is hydrogenated in the presence of a noble metal catalyst to obtain 2-amino-2' carboxydiphenyl sulphide [X]. The 2-amino-2'-carboxydiphenylsulphide [X] is reacted with halide or oxyhalide of the phosphorous to obtain in situ iminohalide [VI], which further reacts as such with 1-hydroxyethoxyethylpiperazine or condenses with piperazine to obtain 11-piperazinyldi.benzo[b,f][1,4]thiazepine [XIX] which further reacts with 2- chloroethoxyethanol or reacts with 1-(2-hydroxyethyl)piperazine to give 11-[4-(2-hydroxyethyl)piperazine-1-yl]dibenzo[b,f][ 1,4]thiazepine [XXXI] which further converts to an intermediate 11-[4-(2-substitutedethyl)piperazin-1- yl)dibenzo[b,f][1,4]thiazepine wherein the substituent at the 2-position is selected from mesyloxy or tosyloxy or halo group [XXXII] followed by reaction with ethylene glycol to give quetiapine [1].
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Page/Page column 9; 14; 15
(2008/06/13)
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- PROCESS FOR PREPARING QUETIAPINE FUMARATE
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Provided is a novel synthesis of quetiapine, and pharmaceutically acceptable salts thereof, in which an alkali metal halide or siliyl halide is included in the reaction mixture.
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Page/Page column 12; 18-20; 21-22
(2008/06/13)
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- Processes for preparing quetiapine and salts thereof
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The present invention provides herein a two-step process for preparing pharmaceutically pure quetiapine and salts thereof by obtaining the starting material 11-chloro-dibenzo-thiazepine followed by reacting the 11-chloro-dibenzo-thiazepine with 1-(2-hydroxyethoxy)ethylpiperazine, or its salt, in the presence of an inorganic or organic base in an organic solvent or in a two-phase solvent system. The present invention provides also a novel, one-pot reaction process for preparing pharmaceutically pure quetiapine and salts thereof. The two processes provided herein can be easily, conveniently and inexpensively scaled-up.
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Page/Page column 4; 9
(2010/10/20)
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- INDUSTRIAL PREPARATION OF 11-[4-{2-(2-HYDROXYETHOXY ETHYL}-1-PIPERAZINYL] DIBENZO [b,f]-1[1, 4] THIAZEPINE
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Disclosed herein is an industrial process for preparation of Quetiapine by the reaction of 11-piperazinyldibenzo[b,f][1,4]-thiazepine or its salt with 2-(2-chloroethoxy)ethanol in presence of an inorganic base in aqueous condition to form 11-[4-{2-(2-hydroxyethoxy)ethyl}-1-piperazinyl] dibenzo [b,f]-[1,4]thiazepine. The quetiapine free base obtained is further converted to its hemi-fumarate salt.
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Page/Page column 6
(2008/06/13)
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- SYNTHESIS OF 11-(4[-(2-HYDROXYETHOXY)ETHYL]-PIPERAZINYL)-DIBENZO[b,f][1,4]THIAZEPINE AND ITS FUMARATE SALT
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The invention is directed a method for synthesizing l l-(4-[2-(2- hydroxyethoxy)ethyl]-piperazinyl)-dibenzo[b,f] [l,4]thiazepine (quetiapine) and for recovering quetiapine as its fumarate salt in which dibenzo[b,f][l,4]thiazepine- l l(10H)one is chlorinated in the presence of a trialkyl amine base using a slight molar excess of phosphorous oxychloride to produce l l-chloro-dibenzo[b,f] [l,4]thiazepine which then is alkylated with piperazine to l l-piperazinyldibenzo[b,f] [l,4]thiazepine, which finally is alkylated with 2-(2-chloroethoxy)ethanol.
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Page/Page column 14
(2008/06/13)
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- PHOSPHORIC ACID SALT OF QUETIAPINE
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The invention relates to new salts of 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy] ethanol derived from phosphoric acid and obtainable in crystalline form, to a process for their preparation and to pharmaceutical compositions containing them. The new salts are useful in the treatment or prevention of psychotic disorders.
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Page/Page column 8
(2008/06/13)
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- PHARAMACEUTICAL COMPOUNDS
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The invention relates to new salts of 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy] ethanol with organic acids and obtainable in crystalline form, to a process for the preparation of the new salts and to pharmaceutical compositions containing them. The new salts are useful in the treatment or prevention of psychotic disorders.
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Page/Page column 8
(2010/11/08)
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- Method for the preparation of quetiapine by reductive N-alkylation of 11-Piperazinodibenzo(B,F) (1,4)Thioazepin with an aldehyde
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The invention relates to a process for preparing quetiapine of formula I by reductive N-alkylation of 11-piperazinodibenzo[b,f][1,4]thiazepine or its salts of formula II with an aldehyde of formula III. The process is carried out in the presence of a metal borohydride (wherein the metal is chosen from the I or II group of the periodic table) in a temperature range from -10°C to 20°C, preferably from 0°C to 5°C. where X-=Cl-,Br-,ClO3- (R1=Me,Et,Pr,iPr)
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Page/Page column 4
(2008/06/13)
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- PREPARATION METHOD FOR QUETIAPINE
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The present invention discloses a process for the preparation of quetiapine, which comprises the ring closure and deprotection of a compound of the formula (I), as well as novel intermediates in the process.
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Page/Page column 6
(2008/06/13)
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- PREPARATION OF QUETIAPINE
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The present invention discloses a process for the preparation of quetiapine, which comprises the reaction of dibenzo[b,f][1,4]thiazepin-11-ylamine with a compound of the general formula (II) as well as novel intermediates in the process.
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Page/Page column 7
(2010/02/11)
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- PROCEDURE FOR PREPARING A PHARMACEUTICALLY ACTIVE COMPOUND
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The invention relates to a procedure for preparing quetiapine by reaction between a compound of formula (II) and a compound of formula (III), in which X means a leaving group and P a protective group of alcohols resistant to alkaline conditions, in the presence of a base, followed by a step of deprotection and, optionally, obtaining a pharmaceutically acceptable salt thereof. Said procedure permits the obtaining of quetiapine with a high degree of purity under soft temperature conditions, with short reaction times and avoiding the use of toxic solvents.
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Page/Page column 10
(2008/06/13)
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- PREPARATION OF QUETIAPINE
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The present invention discloses a process for the preparation of quetiapine, which comprises the ring closure of a compound of the formula shown below, as well as novel intermediates in the process.
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Page/Page column 10
(2008/06/13)
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- Process for the preparation of a thiazepine derivative
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The present invention relates to a process for the preparation of biologically active thiazepine derivative. The present invention more particularly, relates to an improved process for the preparation of dibenzo[b,f][1,4]thiazepine derivative of formula (I).
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Page/Page column 6
(2010/02/11)
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- SYNTHESIS OF QUETIAPINE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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Provided are a novel synthesis of quetiapine, quetiapine made by such process and its acid addition salts, and pharmaceutical composition comprising quetiapine so mad, or its acid addition salts.
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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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- Behavioral approach to nondyskinetic dopamine antagonists: Identification of Seroquel
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A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-Potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-Induced climbing and antagonism of apomorphine-Induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-Sensitized Cebus monkeys. Initial examination of a few close cogeners of I enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias whereas its N-2-(2-Hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-Substituted analogues of 6-(piperazin-1-yl)-11H-Dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]-thiazepines and -Oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]-piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-Substituted analogues were found to be good apomorphine antagonists but all were dyskinetic.
- Warawa,Migler,Ohnmacht,Needles,Gatos,McLaren,Nelson,Kirkland
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p. 372 - 389
(2007/10/03)
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- NOVEL DIBENZOTHIAZEPINE ANTIPSYCHOTIC
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11-[4-[2-(2-Hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo[b,f][1, 4 ] thiazepine is disclosed as a neuroleptic with a much reduced incidence of side effects such as acute dystonia and dyskinesia and tardive diskinesia.
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- Process for the preparation of a thiazepine compound
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11-(4-[2-(2-Hydroxyethoxy)ethyl]-piperazinyl)-dibenzo[b,f][1,4]thiazepine and the salts thereof possess antiandropaninergic activity, especially antipyschotic activity, and are prepared by reacting 11-piperazinyldibenzo[b,f][1,4]thiazepine with a compound of the formula:-, X-CH2-CH2-O-CH2-CH2OH, (wherein X represent an atom or group removable as an anion and, where appropriate further reaction of the product obtained to yield the free base or salt as desired.
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