Process for preparing voriconazole
AssigneeHanmi Science Co., Ltd.
InventorsYoung Ho Moon, Moon Sub Lee, Jae Ho Yoo, Ji Sook Kim, Han Kyong Kim, Chang Ju Choi, Young Kil Chang, Gwan Sun Lee
Life of this patent
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Abstract
Optically pure voriconazole can be prepared in a high yield by a) subjecting 1-(2,4-difluorophenyl)-2(1H-1,2,4-triazol-1-yl)ethanone to Reformatsky-type coupling reaction with a substituted thiopyrimidine derivative to obtain a desired (2R,3S)/(2S,3R)-enantiomeric pair; b) removing the thiol derivative from the enantiomer to obtain racemic voriconazole; and c) isolating the racemic voriconazole by way of optical resolution using an optically active acid.
Claims7
A process for preparing voriconazole of formula (I), which comprises the steps of:
- a) subjecting the compound of formula (IV) to Reformatsky-type coupling reaction with a compound of formula (V) to obtain a compound of formula (III) which is a (2R,3S)/(2S,3R)-enantiomeric pair;
- b) removing the thiol derivative from the compound of formula (III) to obtain the racemic voriconazole of formula (II);
- and
- c) isolating the compound of formula (II) by way of optical resolution using an optically active acid:
- wherein,
- R is C1-C4 alkyl, benzothiazolyl, benzoxazolyl, imidazolyl, 1-methylimidazolyl, thiazolyl, pyridyl, pyrimidyl, phenyl, or phenyl having one or two substituents selected from the group consisting of halogen, nitro and methoxy.
A compound of formula (V):
- wherein,
- R is C1-C4 alkyl, benzothiazolyl, benzoxazolyl, imidazolyl, 1-methylimidazolyl, thiazolyl, pyridyl, pyrimidyl, phenyl, or phenyl having one or two substituents selected from the group consisting of halogen, nitro and methoxy.
An enantiomeric compound of formula (III):
- wherein,
- R is C1-C4 alkyl, benzothiazolyl, benzoxazolyl, imidazolyl, 1-methylimidazolyl, thiazolyl, pyridyl, pyrimidyl, phenyl, or phenyl having one or two substituents selected from the group consisting of halogen, nitro and methoxy.
Dependencies are inferred from the claim text.