- 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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- 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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- 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 0046; 0047
(2016/12/01)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF TRAZODONE AND HYDROCHLORIDE SALT THEREOF
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The present invention provides an improved process for preparation of the substantially pure trazodone and its hydrochloride salt. The process comprises reaction of the compound- Π (as described) with the compound-Ill (as described) optionally in the presence of an inorganic base, and a catalyst; wherein in the said process the trazodone free base and/or its hydrochloride salt are isolated by precipitation at lower temperature. The improved process for the preparation of trazodone hydrochloride (the compound I) provides the product with total amount of alkylating substances (as described herein) as impurity in less than 10 ppm. The improved process for the preparation of trazodone hydrochloride (the compound I) provides the product with total amount of l-(3-chlorophenyl)-4-(3-chloropropyl) piperazine as an impurity in less than 2.5 ppm.
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Page/Page column 19; 20
(2015/08/06)
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- TRAZODONE AND TRAZODONE HYDROCHLORIDE IN PURIFIED FORM
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A process of production of trazodone or trazodone hydrochloride that comprises the steps of: (a) preparing an organic phase comprising trazodone in at least one organic solvent; (b) preparing an aqueous phase comprising at least one basic compound; (c) mixing said aqueous phase with said organic phase; (d) heating at a temperature o at least 40°C for at least 30 minutes; (e) recovering said trazodone; and, optionally, (f) treating said trazodone with hydrochloric acid to obtain trazodone hydrochloride. Trazodone or trazodone hydrochloride comprising less than 15 ppm of alkylating substances, and a pharmaceutical composition comprising said trazodone hydrochloride.
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Page/Page column 13-16
(2009/04/25)
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