Method for the production of praziquantel

Patent metadata

Field	Value
Publication number	US-10160758-B2
Application number	US-201515528282-A
Country	US
Kind code	B2
Filing date	Nov 17, 2015
Priority date	Nov 21, 2014
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

The present invention relates to a method for the racemization of enantiomerically pure or enantiomerically enriched Praziquantel under basic conditions and a method for the production of (R)-Praziquantel in enantiopure or enantiomerically enriched form, which comprises the racemization method.

First claim

The invention claimed is:

1. A method which comprises racemization of enantiomerically pure or enantiomerically enriched Praziquantel:

wherein a base is used and the base is a tertiary alkyl alkoxide.

2. A method according to claim 1 , wherein the tertiary alkali alkoxide used for the racemization is potassium tert.-butoxide.

3. A method according to claim 1 , wherein the racemization is a performed in a dipolar aprotic reaction medium.

4. A method according to claim 3 , wherein the dipolar aprotic reaction medium is selected from the group consisting of N-Methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, methyltetrahydrofuran, dioxane and mixtures thereof in all ratios.

5. A method according to claim 1 , wherein the racemization is performed at a temperature in a range between −50° C. and +40° C.

6. A method according claim 1 , wherein the amount of base used for the racemization is in the range of 0.05 eq to 1.5 eq.

7. A method according to claim 1 , wherein:
the racemization is performed in a dipolar aprotic reaction medium selected from a group consisting of N-Methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, methyltetrahydrofuran, dioxane and mixtures thereof in all ratios;
the amount of base used for the racemization is in the range between 0.05 eq to 1.5 eq;
the racemization is performed at a temperature in the range between −50° C. and +40° C.

8. A method for the production of (R)-Praziquantel in enantiopure or enantiomerically enriched form, comprising following steps:
a. Racemization of enantiomerically pure or enantiomerically enriched (S)-Praziquantel according to claim 1 ; and
b. Chiral resolution of the mixture of the enantiomers (S)-(I) and (R)-Praziquantel obtained in a).

9. A method according to claim 8 , wherein the chiral resolution according to step b) is performed using chromatography.

Assignees

• Merck Patent Gmbh

Inventors

• Waechtler Andreas
• Saleh-Kassim Hadia
• Jasper Christian
• Kolb Joern
• Maillard David

Classifications

• C07B2200/07

  Optical isomers · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07B55/00

  Racemisation; Complete or partial inversion · CPC title

• C07C31/30

  Alkali metal or alkaline earth metal alcoholates · CPC title

• C07B57/00

  Separation of optically-active compounds · CPC title