公开(公告)号：KR1020100083437A

公开(公告)日：2010-07-22

申请号：KR1020090002804

申请日：2009-01-13

Applicant: 서울대학교산학협력단

Inventor： 서영거 ,  백승만

IPC: C07D455/06 ,  A61K51/00 ,  A61P43/00

Abstract: PURPOSE: A method for preparing alpha-dihydrotetrabenazine and tetrabenazine is provided to improve a method for preparing one side isomer by HPLC. CONSTITUTION: A method for preparing alpha-dihydrotetrabenazine comprises: a step of performing amidation of a compound of chemical formula 3 with 4-methyvaleic acid to obtain a compound of chemical formula 4; a step of substituting the compound of chemical formula 4 with aldehyde to obtain a compound of chemical formula 5; a step of adding TBSCI and DBU to the compound of chemical formula 5 to obtain a compound of chemical formula 6; a step of reacting the compound of chemical formula 6 under the presence of LiHMDS, i-PrMgCl, or t-butylMgCl and toluene or benzene to obtain a compound of chemical formula 7; a step of adding TsOH or HI to the compound of chemical formula 7 under the presence of benzene or THF solvent to obtain a compound of chemical formula 8; and a step of reducing the compound of chemical formula 8 to obtain a compound of chemical formula 2.

Abstract translation: 目的：提供一种制备α-二氢丁苯那嗪和丁苯那嗪的方法，以改进通过HPLC制备单面异构体的方法。 构成：制备α-二氢丁苯并嗪的方法包括：用4-甲基乙酰胺进行化学式3的化合物的酰胺化以获得化学式4的化合物的步骤; 用醛取代化学式4的化合物以获得化学式5的化合物的步骤; 向化学式5的化合物中加入TBSCI和DBU以获得化学式6的化合物的步骤; 在LiHMDS，i-PrMgCl或叔丁基MgCl 3和甲苯或苯的存在下使化学式6的化合物反应以获得化学式7的化合物的步骤; 在苯或THF溶剂的存在下，向化学式7的化合物中加入TsOH或HI的步骤，得到化学式8的化合物; 以及还原化学式8的化合物以获得化学式2的化合物的步骤。

公开(公告)号：KR101102957B1

公开(公告)日：2012-01-10

申请号：KR1020090002804

申请日：2009-01-13

Applicant: 서울대학교산학협력단

Inventor： 서영거 ,  백승만

IPC: C07D455/06 ,  A61K51/00 ,  A61P43/00

Abstract: 본 발명은 알파-디하이드로테트라베나진 및 테트라베나진의 제조방법에 관한 것으로서, 본 발명의 제조방법에 의하여 알파-디하이드로테트라베나진 또는 테트라베나진을 직접적으로 제조할 수 있다. 본 발명의 제조방법에 의하여, 라세미체를 제조한 후 효소나 HPLC를 이용한 분리방법으로 한 쪽 이성질체를 제조하는 종래의 제조방법을 획기적으로 개선되어, 효과적으로 알파-디하이드로테트라베나진 또는 테트라베나진을 입체선택적으로 제조할 수 있다.
알파-디하이드로테트라베나진, 테트라베나진