Preparation method of Stendra

Abstract

The invention provides a preparation method of Stendra. The method comprises the following steps that starting materials 4-[(3-chloro-4-methoxyphenyl)methylamino]-2-[(S)-2-hydroxymethyl pyrrole-1-base]pyrimidine-5-carboxylic acid and 2-pyrimidinemethanamine are dissolved into a reactive solvent methylbenzene, a boric acid porphyrin catalyst is aded, heating and stirring are conducted to a reflux state, and the Stendra is obtained through catalysis. Accordingly, boric acid porphyrin serves as the catalyst, catalysis is conducted directly to synthesize the Stendra directly. The dosage of the catalyst is low, the reaction activity is high, operation is relatively simple, after the reaction is finished, a target product is likely to be separated from the catalyst, the difficulty of separationand purification of later products is greatly lowered, the recovered catalyst can be recycled, and the preparation cost can be significantly lowered, and the whole catalytic reaction has the advantages of being simple, environmentally friendly and the like, the input cost such as manpower and raw materials is significantly lowered, and large-scale industrial production is facilitated.

Description

technical field [0001] The invention relates to the technical field of medicine production, in particular to a preparation method of avanafil. Background technique [0002] Avanafil CAS registration number: 330784-47-9, see the compound structure figure 1 . It is a drug developed by the American Vivus (Vivus) pharmaceutical company authorized by Japan Tanabe Mitsubishi Pharmaceutical Co., Ltd. for the treatment of male erectile dysfunction. On April 27, 2012, it was approved by the US FDA and launched in the United States under the trade name of Stendra. [0003] Depend on figure 2 It can be seen that the key step in the synthesis of avanafil is the fourth step chemical reaction: that is, from the intermediate 3,4-[(3-chloro-4-methoxyphenyl)methylamino]-2-[(S)- 2-Hydroxymethylpyrrol-1-yl]pyrimidine-5-carboxylic acid and starting material 3,2-aminomethylpyrimidine for amidation splicing. Specifically, the amide is prepared by condensation of a carbodiimide condensing ag...

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Problems solved by technology

[0004] The problem that the above-mentioned amide synthesis method exists is: the use of activating reagent in the reaction all will be stoichiometric, sometimes even greatly excessive; And after acylation reaction is finished, change into useless by-product again, belong to consumption reagent, and " The principle of "atom economy" is contrary to the principle; the separation of by-products and amides produced by activating reagents is sometimes difficult and cumbersome; in addition, most of the activating reagents are expensive, and the cost problem will become particularly prominent when preparing amide products on a large scale

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