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Traboxopine hydrochloride, EGYT-2509

曲波索平 Chemical Name: (R,S)-2-Chloro-12H-dibenzo[d,g][1,3,6]dioxazocine 12-(N,N,beta-trimethylpropanamine) monohydrochloride
CAS No. 70133-85-6, 103624-59-5 (free base)
项目整合开发状态: Phase II
项目研究机构: Egis (Originator)
合成路线:5-Chloro-2-methoxy-N-formylaniline (I) is reacted with 2-bromoanisole at 220 C in the presence of Na2CO3 and Cu(I)Br in Dowtherm A to give the diphenylamine (II),which is demethylated with anhydrous AlCl3 in chlorobenzene.The product (III) is cyclized with CH2Br2 in refluxing 2-butanone in the presence of K2CO3,then hydrolyzed with NaOH in boiling ethanol to give the dioxazocine (IV).The lat ter is condensed with 3-dimethylamino-2-methyl-1-chloropropane (V) in refluxing xylene in the presence of NaOH and the resulting base (VI) transtormed to EGYT-2509 by treatment with HCl in isopropanol.
📌 参考资料/链接:
参考文献标题:Dibenzo[d,g][1,3,6]dioxazocine derivs.
文献作者:Grasser,K.; Kiszelly,E.; Kos骳zky,I.; Pet骳z,L.; R髗sa,L.(Egis Pharmaceuticals Ltd.)
参考来源:DE 2833892; GB 2001980; US 4208410

📄 详细内容


合成路线:5-Chloro-2-methoxy-N-formylaniline (I) is reacted with 2-bromoanisole at 220 C in the presence of Na2CO3 and Cu(I)Br in Dowtherm A to give the diphenylamine (II),which is demethylated with anhydrous AlCl3 in chlorobenzene.The product (III) is cyclized with CH2Br2 in refluxing 2-butanone in the presence of K2CO3,then hydrolyzed with NaOH in boiling ethanol to give the dioxazocine (IV).The lat ter is condensed with 3-dimethylamino-2-methyl-1-chloropropane (V) in refluxing xylene in the presence of NaOH and the resulting base (VI) transtormed to EGYT-2509 by treatment with HCl in isopropanol.

参考文献标题:EGYT-2509
文献作者:Nogradi,M.
参考来源:Drugs Fut 1986,11(12),1027


合成路线:5-Chloro-2-methoxy-N-formylaniline (I) is reacted with 2-bromoanisole at 220 C in the presence of Na2CO3 and Cu(I)Br in Dowtherm A to give the diphenylamine (II),which is demethylated with anhydrous AlCl3 in chlorobenzene.The product (III) is cyclized with CH2Br2 in refluxing 2-butanone in the presence of K2CO3,then hydrolyzed with NaOH in boiling ethanol to give the dioxazocine (IV).The lat ter is condensed with 3-dimethylamino-2-methyl-1-chloropropane (V) in refluxing xylene in the presence of NaOH and the resulting base (VI) transtormed to EGYT-2509 by treatment with HCl in isopropanol.

参考文献标题:Synthesis of 14C-labelled dibenzo[d,g][1,3,6]dioxazocine derivatives (EGYT-2474 and EGYT 2509)
文献作者:Birkas-Faigl,E.; et al.
参考来源:J Label Compd Radiopharm 1985,221061


合成路线:5-Chloro-2-methoxy-N-formylaniline (I) is reacted with 2-bromoanisole at 220 C in the presence of Na2CO3 and Cu(I)Br in Dowtherm A to give the diphenylamine (II),which is demethylated with anhydrous AlCl3 in chlorobenzene.The product (III) is cyclized with CH2Br2 in refluxing 2-butanone in the presence of K2CO3,then hydrolyzed with NaOH in boiling ethanol to give the dioxazocine (IV).The lat ter is condensed with 3-dimethylamino-2-methyl-1-chloropropane (V) in refluxing xylene in the presence of NaOH and the resulting base (VI) transtormed to EGYT-2509 by treatment with HCl in isopropanol.

参考文献标题:Conformational analysis of the dibenzo[d,g][1,3,6]dioxazocine skeleton
文献作者:Farkas,M.; et al.
参考来源:J Mol Struct 1985,131131


合成路线:5-Chloro-2-methoxy-N-formylaniline (I) is reacted with 2-bromoanisole at 220 C in the presence of Na2CO3 and Cu(I)Br in Dowtherm A to give the diphenylamine (II),which is demethylated with anhydrous AlCl3 in chlorobenzene.The product (III) is cyclized with CH2Br2 in refluxing 2-butanone in the presence of K2CO3,then hydrolyzed with NaOH in boiling ethanol to give the dioxazocine (IV).The lat ter is condensed with 3-dimethylamino-2-methyl-1-chloropropane (V) in refluxing xylene in the presence of NaOH and the resulting base (VI) transtormed to EGYT-2509 by treatment with HCl in isopropanol.
参考文献标题:Synthesis and CNS-activity of dibenzo[d,g][1,3,6]dioxazocines
文献作者:Rozsa,L.; Petocz,L.; Grasser,K.; Kosoczky,I.; Kiszelly,E.
参考来源:VIIth Symp Med Chem (Sept 2-5,Torremolinos) 1980,P 175


产品链接: CAS No. 70133-85-6››

产品链接: CAS No.103624-59-5››