Optical pure 1,3-alkamine compound as well as preparation method and application thereof in preparing Dapoxetine and analogues thereof

Abstract

The invention specifically relates to an optical pure 1,3-alkamine compound as well as a preparation method and application thereof in preparing corresponding optical pure 1,3-alkamine and further preparing Dapoxetine and analogues thereof, belonging to the technical field of organic chemistry. The 1,3-alkamine compound is as shown in a formula I.

Description

technical field The invention belongs to the technical field of organic chemistry, and particularly relates to optically pure 1,3-aminoalcohol compounds, a preparation method and an application in preparing dapoxetine and its analogs. Background technique Dapoxetine ((S)-(+)-N, N-Dimethyl-3-(1-naphthyloxy)-1-phenylpropylamine, 1) was originally an antidepressant developed by Eli Lilly Company in 1992. It is a A selective serotonin reuptake inhibitor (SSRI). February 2009 as a drug for the treatment of male premature ejaculation (PE) (Prilig TM ) first launched in Finland and Sweden, which is the world's first oral treatment for this indication. It was listed as one of the five most promising drugs already on the market or under approval by Thomson Reuters (Thomson Reuters) quarterly report on major progress in global drug development in the first quarter of 2009. Optically pure dapoxetine mainly obtains the racemate through different synthetic routes and adopts the met...

AI Technical Summary

Problems solved by technology

However, these splitting methods are inefficient and the defects of large waste still exist

There are also some studies on the synthesis of (S)-3-amino-3-phenylpropanol using asymmetric synthesis methods, such as L-diethyl tartrate (Tetrahedron, 2009, 65, 2605-2609) or 1,4-diol (US 6207862) as a raw material, and eventually optically active 1,3-aminoalcohols can be synthesized, but the reaction is complicated, there are many steps, the total yield is low, and there is no ee value data

Taken together, the current methods for synthesizing (S)-3-amino-3-phenylpropanol are not satisfactory, either with high cost, large waste, or insufficient optical purity, and it is necessary to further develop economical and applicable routes

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