Method for preparing pyridino-triazolone compound through flow chemistry

Abstract

The invention relates to a method for preparing a pyridino- triazolone compound (II) through flow chemistry. The method comprises the following steps: a hydrazide compound (I) is dissolved in an organic solvent, the solution is placed in a first storage tank, an oxidantis dissolved in the organic solvent, and the solution is placed in a second storage tank; and aterials in the first storage tank and the second storage tank are conveyed through metering pumps respectively and enter a mixer to be mixed, reaction liquid obtained through mixing continuously enters a tubular reactor to be subjected to oxidation rearrangement reaction, the temperature of oxidation rearrangement is 0-70 DEG C, the retention time of the mixed reaction liquid in the tubular reactor is 0.1-10 h, material liquid obtained after reaction enters a receiving tank and is subjected to post-treatment, and after-treatment is conducted on the material liquid to obtain the product (II). In the tubular reaction, the material back mixing is less, the mass transfer and heat transfer efficiency is high, and the side reaction is obviously reduced; a reaction system is simple, raw materials, especially hydrazide compounds, are easily obtained, a substrate does not need to be prepared in multiple steps, and the total yield is relatively high; and the continuous tubular reaction can accurately control reaction parameters and has an automation prospect;.

Description

technical field [0001] The invention relates to a method for preparing pyridotriazolone compounds by flow chemistry. Background technique [0002] Pyridotriazolones are an important class of nitrogen-containing heterocyclic compounds in pharmacy and pesticides due to their special chemical structure and biological activity. At present, there have been many reports on active molecules containing the core of pyridotriazolone. For example, the drug trazodone is a pyridotriazolone antidepressant, and its effect is similar to that of tricyclics and monoamine oxidase inhibitors (MAOI). It is the first-line drug for clinical treatment of depression. (J. Med. Chem. 1985, 28, 1394-1398; J. Med. Chem., 1999, 42, 336-345; Bioorg. Med. Chem. Lett. 2013, 23, 3983-3987; Bioorg. Med. Chem. 2014, 22, 3414-3422; Bioorg. Med. Chem. Lett. 2015, 25 5524–5528; Bioorg. Med. Chem. Lett. 2016, 26, 3207-3211). [0003] At present, the synthesis of substituted pyridotriazolones is mainly through t...

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Problems solved by technology

[0004] The present invention synthesizes substituted triazolone compounds under the condition of one-step oxidative rearrangement of hydrazide compounds in the pipeline, and solves the problem that traditional synthesis methods require high temperature and large steric hindrance to replace triazolones that cannot be synthesized

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