Method for preparing Tadalafil by one-pot method

Abstract

The invention discloses a method for preparing Tadalafil by a one-pot method. The method for preparing the Tadalafil by the one-pot method comprises the steps that D-Tryptophan methyl ester hydrochloride and piperonal are used as starting materials, and a single-configuration high-purity compound I hydrochloride is obtained through a Pictet-Spengler reaction; the compound I hydrochloride is subjected to an acylation reaction with chloroacetyl chloride in an organic base system of an aprotic solvent to obtain a mixed reaction solution; and the mixed reaction solution is directly added to a methylamine solution to undergo an aminolysis cyclization reaction without treatment, and the mixture is subjected to cooling crystallization to obtain the Tadalafil after the reaction. According to the method for preparing the Tadalafil by the one-pot method, the usage amount of the solvent is reduced, the amount of waste liquid discharge is effectively controlled, and environmental protection is facilitated; the production cycle is shortened, and the process efficiency is improved; and the yield is improved, and the cost is reduced. Compared with an existing process route, the method for preparing the Tadalafil by the one-pot method is more environmentally friendly, more efficient and lower in cost, and is more suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of preparation of chemical raw materials, and in particular relates to a method for preparing tadalafil by a one-pot method. Background technique [0002] Tadalafil, the chemical name is (6R-12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12, 12a-hexahydropyrazino[1',2'-1,6]-pyrido[3,4-b]indole-1,4-dione; molecular weight: 389.41; molecular formula C 22 h 19 N 3 o 4 ;The structural formula is as follows: [0003] [0004] Tadalafil is a selective and reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase 5 (PDE5). Tadalafil was originally developed by Glaxo Wellcome Laboratories, then transferred to ICOS, and then ICOS and Eli Lilly jointly developed it. In 2003, it was approved by the U.S. FDA to go on the market. The product name is "Cialis", and the indication is male erectile dysfunction (ED). It is also approved in the United States and Europe for benign prostatic hyper...

AI Technical Summary

Problems solved by technology

[0012] In summary, the above synthetic methods all need to obtain the solid intermediate product compound II, and then proceed to the next step of reaction, which makes the reaction time longer, consumes more reagents, and increases waste liquid discharge, which is not conducive to environmental protection; consumes more energy and manpower prolong the production cycle, which is not conducive to cost control and process efficiency improvement; the yield is not high, the weight yield is the lowest 45.2%, the highest 90.0%

Although there are many methods for preparing tadalafil at present, there is no bibliographical report that the intermediate product compound II does not need to be processed and can be continuously reacted to obtain the method of tadalafil

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