- CONTINUOUS PROCESS FOR THE PREPARATION OF TRAZODONE
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The present invention relates to an improved process for the preparation of trazodone. In particular, the present invention relates to a continuous process for the preparation of trazodone. More in particular, the present invention relates to a new method for the preparation of trazodone, said method comprising at least one step consisting of a continuous process performed in a flow reactor.
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Page/Page column 25-29
(2019/08/29)
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- Microwave-assisted synthesis of trazodone and its derivatives as new 5-HT1A ligands: Binding and docking studies
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Trazodone, a well-known antidepressant drug widely used throughout the world, works as a 5-hydroxytryptamine (5-HT2) and α1-adrenergic receptor antagonist and a serotonin reuptake inhibitor. Our research aimed to develop a new method for the synthesis of trazodone and its derivatives. In the known methods of the synthesis of trazodone and its derivatives, organic and toxic solvents are used, and the synthesis time varies from several to several dozen hours. Our research shows that trazodone and its derivatives can be successfully obtained in the presence of potassium carbonate as a reaction medium in the microwave field in a few minutes. As a result of the research work, 17 derivatives of trazodone were obtained, including compounds that exhibit the characteristics of 5-HT1A receptor ligands. Molecular modeling studies were performed to understand the differences in the activity toward 5-HT1A and 5-HT2A receptors between ligand 10a (2-(6-(4-(3-chlorophenyl)piperazin-1-yl)hexyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one) (5-HT1A Ki = 16 nM) and trazodone. The docking results indicate the lack of the binding of ligand 10a to 5-HT2AR, which is consistent with the in vitro studies. On the other hand, the docking results for the 5-HT1A receptor indicate two possible binding modes. Crystallographic studies support the hypothesis of an extended conformation.
- Jaskowska, Jolanta,Zar eba, Przemys?aw,Sliwa, Pawe?,Pindelska, Edyta,Sata?a, Grzegorz,Majka, Zbigniew
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- METHOD FOR THE PREPARATION OF TRAZODONE
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A method for the preparation of trazodone of formula III, in the reaction of 2-(3- halogenopropyl)[l,2,4]triazolo[4,3-a]pyridin-3(2H)-one of formula la or formula lb with l-(3-chlorophenyl)piperazine hydrochloride of formula II consists in, that the reaction of trazodone synthesis is carried out under solvent-free conditions, in the presence of microwave radiation. The reaction is carried out at the molar ratio of 2-(3- halogenopropyl)[l,2,4]triazolo[4,3-a]pyridin-3(2H)-one to l-(3- chlorophenyl)piperazine hydrochloride of from 1 : 1 to 1.2, and using potassium carbonate having the graining of 20 - 900 μηι, which amount in the reaction mixture is from 35 to 45 % by weight of the mixture, and using a PTC catalyst selected from TBAB (tetrabutylammonium bromide), TEAC (tetraethylammonium chloride), DABCO (l,4-diazabicyclo[2.2.2]octane), in an amount of 1 to 4 % by weight of the mixture. After the synthesis is completed, to the reaction mixture water is added and stirred and then the liquid phase is separated from the containing trazodone solid phase.
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Page/Page column 4
(2018/10/19)
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- Preparation method of trazodone hydrochloride
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The invention is applicable to the field of chemistry and chemical engineering and provides a preparation method of trazodone hydrochloride. The preparation method comprises the following steps: mixing N-(3-chloro-phenyl)-N'-(3-chloropropyl)-piperazine hydrochloride and 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one in a solvent; adding an alkali, and heating and reflowing; carrying out heat filtering into a reaction system, adding alkali liquid and heating and reflowing again in sequence; crystallizing to obtain trazodone; taking the trazodone to react with hydrochloric acid to obtain the trazodone hydrochloride. According to the preparation method of the trazodone hydrochloride, provided by the invention, the total yield of the product is improved, and the content of an impurity N-(3-chloro-phenyl)-N'-(3-chloropropyl)-piperazine is remarkably reduced, so that the industry limitation requirements can be directly met. The preparation method has simple flow steps so that the production cost is reduced; the process is stable and industrial production can be carried out.
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Paragraph 0042; 0043
(2016/12/01)
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- Efficient copper-catalyzed cross-coupling of 1-Boc-piperazine with aryl iodides and its application in the synthesis of trazodone
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A convenient and practical strategy is developed for the cross-coupling of N-Boc protected piperazines with aryl iodides using CuBr/1,1′-bi-2- naphthol as the catalyst and K3PO4 as the base. The protocol affords N-arylated piperazine products in moderate to good yields under the optimized conditions. The application of this catalytic system to the synthesis of trazodone is also successfully demonstrated using commercially available substrates.
- Yong, Fui-Fong,Teo, Yong-Chua,Tan, Khee-Ngiap
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p. 5332 - 5334
(2013/09/12)
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- SUBSTITUTED TRIAZOLOPYRIDINES
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Disclosed herein are substituted triazolopyridine serotonin reuptake modulators and/or 5-HT receptor modulators of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 27
(2009/09/05)
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