Syn-2869
4-[4-[(1R,2R)-2-(2,4-二氟苯基)-2-羟基-1-甲基-3-(1H-1,2,4-三唑-1-基)丙基]-1-哌拉嗪基]-2-[4-(三氟甲氧基)苯基]-2-[4-(三氟甲氧基)苯]-2,4-二氢-3H-1,2,4-三唑-3-一Chemical Name: 4-[4-[4-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-1-piperazinyl]phenyl]-2-[4-(trifluoromethoxy)benzyl]-2,4-dihydro-3H-1,2,4-triazol-3-one
CAS No. 210562-98-4
项目整合开发状态: Preclinical
项目研究机构: Naeja (Originator), Taiho (Originator)
合成路线:1) The reaction of 1-(4-nitrophenyl)piperazine (I) with tert-butyl dicarbonate (II) and triethylamine in dichloromethane gives 4-(4-nitrophenyl)piperazine-1-carboxylic acid tert-butyl ester (III),which is reduced with H2 over Pd/C,yielding the corresponding 4-amino compound (IV).The reaction of (IV) with phenyl chloroformate (V) and triethylamine in dichloromethane affords the carbamate (VI),which by reaction with hydrazine is converted into the semicarbazide (VII).The cyclization of (VII) with formamidine (VIII) and triethylamine in hot 2-methoxyethanol affords the triazolone (IX),which is condensed with 4-(trifluoromethoxy)benzyl bromide (X) by means of Cs2CO3 in DMF,giving the disubstituted triazolone (XI).The deprotection,elimination of the tert-butoxycarbonyl group,of (XI) with HCl yields the monosubstituted piperazine (XII),which is finally condensed with (2R,3S)-oxirane (XIII) by means of LiClO4 in refluxing acetonitrile.
合成路线:2) The addition of 1-(4-nitrophenyl)piperazine (I) to the chiral oxirane (XIII) as before gives the disubstituted piperazine (XIV),which is hydrogenated with H2 over Pd/C in ethyl acetate,yielding the anilino derivative (XV).The acylation of (XV) with phenyl chloroformate (V) and triethylamine in dichloromethane affords the carbamate (XVI),which is treated with hydrazine to give the semicarbazide (XVII).The cyclization of (XVII) with formamidine (VIII) as before affords the triazolone (XVIII),which is finally condensed with 4-(trifluoromethoxy)benzyl bromide (X) by means of Cs2CO3 in DMF.
📌 参考资料/链接：
参考文献标题:New triazoles as therapeutic agents for fungal infections
文献作者:Ha,C.; Unemi,N.; Nguyen,D.; Furukawa,T.; Sidhu,I.; Daneshtalab,M.; Bathini,Y.; Micetich,R.; Khan,J.; Abel,M.; Salama,S.(Synphar Laboratories Inc.; Taisho Pharmaceutical Co.,Ltd.)
参考来源:EP 0889881; JP 2000507275; WO 9831675
📄 详细内容
合成路线:1) The reaction of 1-(4-nitrophenyl)piperazine (I) with tert-butyl dicarbonate (II) and triethylamine in dichloromethane gives 4-(4-nitrophenyl)piperazine-1-carboxylic acid tert-butyl ester (III),which is reduced with H2 over Pd/C,yielding the corresponding 4-amino compound (IV).The reaction of (IV) with phenyl chloroformate (V) and triethylamine in dichloromethane affords the carbamate (VI),which by reaction with hydrazine is converted into the semicarbazide (VII).The cyclization of (VII) with formamidine (VIII) and triethylamine in hot 2-methoxyethanol affords the triazolone (IX),which is condensed with 4-(trifluoromethoxy)benzyl bromide (X) by means of Cs2CO3 in DMF,giving the disubstituted triazolone (XI).The deprotection,elimination of the tert-butoxycarbonyl group,of (XI) with HCl yields the monosubstituted piperazine (XII),which is finally condensed with (2R,3S)-oxirane (XIII) by means of LiClO4 in refluxing acetonitrile.
合成路线:2) The addition of 1-(4-nitrophenyl)piperazine (I) to the chiral oxirane (XIII) as before gives the disubstituted piperazine (XIV),which is hydrogenated with H2 over Pd/C in ethyl acetate,yielding the anilino derivative (XV).The acylation of (XV) with phenyl chloroformate (V) and triethylamine in dichloromethane affords the carbamate (XVI),which is treated with hydrazine to give the semicarbazide (XVII).The cyclization of (XVII) with formamidine (VIII) as before affords the triazolone (XVIII),which is finally condensed with 4-(trifluoromethoxy)benzyl bromide (X) by means of Cs2CO3 in DMF.
参考文献标题:Syn-2869,novel broad-spectrum antifungal triazole: Synthesis and structure activity relationships
文献作者:Abel,M.D.; Bathini,Y.; Ha,C.; et al.
参考来源:38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998,San Diego) 1998,Abst F-148
合成路线:1) The reaction of 1-(4-nitrophenyl)piperazine (I) with tert-butyl dicarbonate (II) and triethylamine in dichloromethane gives 4-(4-nitrophenyl)piperazine-1-carboxylic acid tert-butyl ester (III),which is reduced with H2 over Pd/C,yielding the corresponding 4-amino compound (IV).The reaction of (IV) with phenyl chloroformate (V) and triethylamine in dichloromethane affords the carbamate (VI),which by reaction with hydrazine is converted into the semicarbazide (VII).The cyclization of (VII) with formamidine (VIII) and triethylamine in hot 2-methoxyethanol affords the triazolone (IX),which is condensed with 4-(trifluoromethoxy)benzyl bromide (X) by means of Cs2CO3 in DMF,giving the disubstituted triazolone (XI).The deprotection,elimination of the tert-butoxycarbonyl group,of (XI) with HCl yields the monosubstituted piperazine (XII),which is finally condensed with (2R,3S)-oxirane (XIII) by means of LiClO4 in refluxing acetonitrile.
合成路线:2) The addition of 1-(4-nitrophenyl)piperazine (I) to the chiral oxirane (XIII) as before gives the disubstituted piperazine (XIV),which is hydrogenated with H2 over Pd/C in ethyl acetate,yielding the anilino derivative (XV).The acylation of (XV) with phenyl chloroformate (V) and triethylamine in dichloromethane affords the carbamate (XVI),which is treated with hydrazine to give the semicarbazide (XVII).The cyclization of (XVII) with formamidine (VIII) as before affords the triazolone (XVIII),which is finally condensed with 4-(trifluoromethoxy)benzyl bromide (X) by means of Cs2CO3 in DMF.
参考文献标题:Syn-2869
文献作者:Fromtling,R.A.; Castar,J.
参考来源:Drugs Fut 1999,24(1),30
产品链接: CAS No. 210562-98-4››