合成路线:The intermediate amino alcohol (XVIII) was prepared by two ways.2-Chloronicotinic acid (XIV) was converted to the corresponding acid chloride (XV) by treatment with oxalyl chloride,and then reacted with potassium tert-butoxide to afford the tert-butyl ester (XVI).Displacement of the chloride group of (XVI) with methanolic methylamine gave rise to the 2-(methylamino)nicotinic ester (XVII),which was then reduced to alcohol (XVIII) employing LiAlH4.Alternatively,2-aminonicotinic acid (XIX) was esterified to (XX) by means of 2-chloro-1,3-dimethylimidazolinium chloride in MeOH.The amino group of (XX) was acylated with formic acetic anhydride to give formamide (XXI).Amino alcohol (XVIII) was then obtained by reduction of amido ester (XXI) in the presence of LiAlH4.Condensation of (XVIII) with 1-chloroethyl chloroformate produced the carbamate alcohol (XXII),which was subsequently esterified with N-Boc-sarcosine (XXIII) by means of EDC yielding (XXIV) (2).Quaternization of the triazole compound (XIII) with the chloroethyl carbamate (XXIV) in the presence of NaI furnished the corresponding triazolium salt,which was finally subjected to acidic Boc group cleavage to produce the title compound.
参考文献标题:N-Substd.carbamoyloxyalkyl-azolium derivs.
文献作者:Shimma,N.; Fukuda,H.; Umeda,I.; Ohwada,J.; Sakaitani,M.; Oikawa,N.; Hayase,T.; Tsukazaki,M.; Mizuguchi,E.(F.Hoffmann-La Roche AG)
参考来源:WO 0132652
合成路线:The intermediate amino alcohol (XVIII) was prepared by two ways.2-Chloronicotinic acid (XIV) was converted to the corresponding acid chloride (XV) by treatment with oxalyl chloride,and then reacted with potassium tert-butoxide to afford the tert-butyl ester (XVI).Displacement of the chloride group of (XVI) with methanolic methylamine gave rise to the 2-(methylamino)nicotinic ester (XVII),which was then reduced to alcohol (XVIII) employing LiAlH4.Alternatively,2-aminonicotinic acid (XIX) was esterified to (XX) by means of 2-chloro-1,3-dimethylimidazolinium chloride in MeOH.The amino group of (XX) was acylated with formic acetic anhydride to give formamide (XXI).Amino alcohol (XVIII) was then obtained by reduction of amido ester (XXI) in the presence of LiAlH4.Condensation of (XVIII) with 1-chloroethyl chloroformate produced the carbamate alcohol (XXII),which was subsequently esterified with N-Boc-sarcosine (XXIII) by means of EDC yielding (XXIV) (2).Quaternization of the triazole compound (XIII) with the chloroethyl carbamate (XXIV) in the presence of NaI furnished the corresponding triazolium salt,which was finally subjected to acidic Boc group cleavage to produce the title compound.
参考文献标题:Development of novel water antifungal,RO0098557
文献作者:Hayase,T.; Tsukazaki,M.; Ohwada,J.; et al.
参考来源:21st Symp Med Chem (Nov 28 2001,Kyoto) 2001,Abst 1P-06
合成路线:The intermediate amino alcohol (XVIII) was prepared by two ways.2-Chloronicotinic acid (XIV) was converted to the corresponding acid chloride (XV) by treatment with oxalyl chloride,and then reacted with potassium tert-butoxide to afford the tert-butyl ester (XVI).Displacement of the chloride group of (XVI) with methanolic methylamine gave rise to the 2-(methylamino)nicotinic ester (XVII),which was then reduced to alcohol (XVIII) employing LiAlH4.Alternatively,2-aminonicotinic acid (XIX) was esterified to (XX) by means of 2-chloro-1,3-dimethylimidazolinium chloride in MeOH.The amino group of (XX) was acylated with formic acetic anhydride to give formamide (XXI).Amino alcohol (XVIII) was then obtained by reduction of amido ester (XXI) in the presence of LiAlH4.Condensation of (XVIII) with 1-chloroethyl chloroformate produced the carbamate alcohol (XXII),which was subsequently esterified with N-Boc-sarcosine (XXIII) by means of EDC yielding (XXIV) (2).Quaternization of the triazole compound (XIII) with the chloroethyl carbamate (XXIV) in the presence of NaI furnished the corresponding triazolium salt,which was finally subjected to acidic Boc group cleavage to produce the title compound.
参考文献标题:RO0098557,a novel water soluble azole prodrug for parenteral and oral administration (I).Design,synthesis,physicochemical properties and bioconversion
文献作者:Ohwada,J.; et al.
参考来源:42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002,San Diego) 2002,Abst F-820
合成路线:The intermediate amino alcohol (XVIII) was prepared by two ways.2-Chloronicotinic acid (XIV) was converted to the corresponding acid chloride (XV) by treatment with oxalyl chloride,and then reacted with potassium tert-butoxide to afford the tert-butyl ester (XVI).Displacement of the chloride group of (XVI) with methanolic methylamine gave rise to the 2-(methylamino)nicotinic ester (XVII),which was then reduced to alcohol (XVIII) employing LiAlH4.Alternatively,2-aminonicotinic acid (XIX) was esterified to (XX) by means of 2-chloro-1,3-dimethylimidazolinium chloride in MeOH.The amino group of (XX) was acylated with formic acetic anhydride to give formamide (XXI).Amino alcohol (XVIII) was then obtained by reduction of amido ester (XXI) in the presence of LiAlH4.Condensation of (XVIII) with 1-chloroethyl chloroformate produced the carbamate alcohol (XXII),which was subsequently esterified with N-Boc-sarcosine (XXIII) by means of EDC yielding (XXIV) (2).Quaternization of the triazole compound (XIII) with the chloroethyl carbamate (XXIV) in the presence of NaI furnished the corresponding triazolium salt,which was finally subjected to acidic Boc group cleavage to produce the title compound.
参考文献标题:Design,synthesis and antifungal activity of a novel water soluble prodrug of antifungal triazole
文献作者:Ohwada,J.; Tsukazaki,M.; Hayase,T.; Oikawa,N.; Isshiki,Y.; Fukuda,H.; Mizuguchi,E.; Sakaitani,M.; Shiratori,Y.; Yamazaki,T.; Ichihara,S.; Umeda,I.; Shimma,N.
参考来源:Bioorg Med Chem Lett 2003,13(2),191
产品链接: CAS No. 338990-84-4››