Scaling of the prospective anti-ulcer API synthesis
DOI:
https://doi.org/10.15587/2519-4852.2018.128885Keywords:
active pharmaceutical ingredient, industrial synthesis, scaling, green chemistry, 1, 2, 4 triazole derivatives, antiulcer agentsAbstract
Aim: the scaling of the laboratory procedure for the synthesis of 5-(4-methylphenylaminomethyl-4-(2-methylphenyl)-1,2,4-triazole-4H-3-ylthioacetic acid 4-methoxyanilide (Triazoprazole) for reproduction in industrial conditions.
Methods. In the development of industrial technology, the efficiency of synthesis (yields at each stage of synthesis, the possibility of carrying out synthesis without isolation of some intermediates), compliance with the principles of green chemistry, and economic feasibility were evaluated. In accordance with the concept of Quality by design, the principles of green chemistry and previously developed algorithms for optimizing industrial synthesis, the theoretical possibilities of synthesis in industrial conditions were analyzed. The optimal reaction conditions are determined experimentally.
Results. As a result of the experimental studies, the possibility of the synthesis of the key intermediate, 5-methylphenylaminomethyl-4- (2-methylphenyl) -1,2,4-triazole-3-thione, without isolation of the intermediate product, has been shown to increase its yield in terms of starting materials . The time for carrying out individual stages of synthesis has been shortened, and the yield and purity of the products remain appropriate. For the alkylation of the key intermediate, the reaction temperature is chosen as the optimum conditions-70 °C, the time is 1 hour, the use of the DMF-alkali system. Such conditions make it possible to ensure a high yield and purity of the final product.
Conclusions: Scaling of the method of synthesis of a potential API with the antiulcer action of 5- (4-methylphenylaminomethyl-4- (2-methylphenyl) -1,2,4-triazole-4H-3-ylthioacetic acid 4-methoxyanilide for use in industrial production using Quality by design concept and "green chemistry"principles was carrying out, The number of stages of synthesis has been reduced and the conditions have been chosen in which the finished product is formed with the maximum yield and acceptable purity
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