Process for preparing intermediates for synthesis of antifungal agents

Abstract

Disclosed is a process for preparing chiral compounds of formula (I) wherein: X<1> and X<2> are independently F or Cl; and E is -SO2R<2>, wherein R<2> is C1-C6 alkyl, -C6H4CH3 or -CF3; its enantiomer and racemates thereof, useful in the synthesis of tetrahydrofuran azole antifungals. Novel compounds of formula (II) or (III) wherein: X<1> and X<2> are independently F or Cl; B represents -C(O)Q* or -CH2OR'; Q* represents a chiral auxiliary group; R'' represents a hydroxy protecting group; and A represents Cl, Br, I, triazolyl or imidazolyl; are also disclosed.

Description

background of the invention

[0001] The invention relates to a preparation method of a chiral intermediate used for preparing trisubstituted tetrahydrofurantriazole or imidazole antifungal agent.

[0002] WIPO publications WO 89 / 04829 and USP 5,039,676 disclose (±)-cis and (±)-trans antifungal compounds represented by the formula: Wherein: a is N or CH; X is F or Cl; Z is lower alkyl, (C 2 -C 8 ) alkanoyl or 2-lower alkyl-3-oxo-1,2,4-triazol-4-yl substituted phenyl. Examples of such compounds are (±)-cis and (±)-trans-1-[4-[[2-(2,4-difluorophenyl)-2-[(1H-1,2,4-tri Azol-1-yl)methyl]tetrahydro-4-furyl]methoxy]phenyl]-4-(1-methylethyl)piperazine.

[0003] In addition, PCT International Application PCT / US 92 / 08981 relates to antifungal compounds represented by the following formula and pharmaceutically acceptable salts thereof: Wherein: X is both F or Cl, or one X is F, and the other is Cl; Y is a group shown in the following formula: where: R 1 for (C 1 -C 10 ) Alkyl, ...

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