Process for preparing voriconazole by using new intermediates
AssigneeDongkook Pharmaceutical Co., Ltd.
InventorsHyuk Chul Kwon, Man Dong Rho, Kyung Hoi Cha
Life of this patent
Estimating the term…
Abstract
Provided is a process for preparing Voriconazole represented by Chemical Formula 1. More particularly, the process for preparing Voriconazole of Chemical Formula 1 includes: carrying out the Reformatsky-type coupling reaction between a ketone derivative of Chemical Formula 4 and a pyrimidine derivative of Chemical Formula 5 to obtain a compound of Chemical Formula 3; reacting the substituents halo and oxysulfonyl with a hydrogen donor to obtain racemic Voriconazole of Chemical Formula 2; and carrying out optical isolation of the racemic Voriconazole by adding an adequate optically active acid thereto to obtain Voriconazole having high optical purity with high cost-efficiency and high yield.
Claims8
A process for preparing Voriconazole of the following Chemical Formula 1, comprising the steps of:
- 1) carrying out the Reformatsky-type coupling reaction between a compound of the following Chemical Formula 4 and a compound of the following Chemical Formula 5 to obtain a compound of the following Chemical Formula 3;
- 2) removing the substituents X1, X2 and OSO2R from the compound of Chemical Formula 3 to obtain racemic Voriconazole of the following Chemical Formula 2, with the proviso that X1 and X2 are not removed when they both represent H;
- and
- 3) separating the isomers of the compound of Chemical Formula 2 with an optically active acid:
- wherein X1 and X2 independently represent H or halo;
- and
- R is C1-C4alkyl or substituted or non-substituted phenyl, wherein the substituted phenyl may be substituted with at least one substituent selected from the group consisting of C1-C4 alkyl, alkoxy, halo, nitro and oxo.
Dependencies are inferred from the claim text.