Synthesis of the methanesulfonates of α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)emenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol,alpha styryl carbinol antifungal agents |
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| Authors: | Jaan A Pesti Jill A Downard Mark D Lauritsen Goss S Kauffman Walter M Bryant George F Huhn John F Arnett Robert E Yule James Segretario Kimberly A Nelson Edward F Gorko Gary O Page Lisa M Lloyd Richard E Olson Christopher S Bamum Joseph J Mrowca |
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| Abstract: | The methanesulfonates of (α-(4-chlorophenyl)-α-1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole-1-ethanol and α-1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol ( 1a, b ) are orally effective α-styryl carbinol derivatives developed for the treatment and prevention of systemic fungal infections. Practical new processes amenable for the large-scale production of these compounds are described. Of note is the selection of dichlorostyrene as a convenient precursor of the styryl portion, modification of a sensitive Grignard addition into a realistic preparative reaction and the use of 1,2,4-triazole simultaneously as a base transfer agent and nucleophile. |
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