842470, GW-842470, AWD-12-281
Chemical Name: N-(3,5-Dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide
CAS No. 247584-20-9
项目整合开发状态: Phase II
项目研究机构: elbion (Originator), GlaxoSmithKline (Licensee)
合成路线:The reaction of 5-methoxyindol (I) with 4-fluorobenzyl chloride in DMF gives 5-methoxy-1-(4-fluorobenzyl)indol (II).This compound is acylated with oxalyl chloride,yielding 5-methoxy-[1-(4-fluorobenzyl)indol-3-yl]glyoxylic acid chloride (III),which is transformed with 4-amino-3,5-dichloropyridine into the corresponding amide (IV).The reaction of (IV) with borontribromide in toluene cleaves the methoxy group,yielding AWD 12-281.
📌 参考资料/链接：
参考文献标题:New hydroxyindoles,their use as phosphodiesterase 4 inhibitors and method for producing same
文献作者:H鰂gen,N.; Kronbach,T.; Plymeropoulos,E.; Marx,D.; Heer,S.; Szelenyi,S.; Egerland,U.; Poppe,H.(Arzneimittelwerk Dresden GmbH)
参考来源:CA 2270301; DE 19818964; WO 9955696
📄 详细内容
合成路线:The reaction of 5-methoxyindol (I) with 4-fluorobenzyl chloride in DMF gives 5-methoxy-1-(4-fluorobenzyl)indol (II).This compound is acylated with oxalyl chloride,yielding 5-methoxy-[1-(4-fluorobenzyl)indol-3-yl]glyoxylic acid chloride (III),which is transformed with 4-amino-3,5-dichloropyridine into the corresponding amide (IV).The reaction of (IV) with borontribromide in toluene cleaves the methoxy group,yielding AWD 12-281.
参考文献标题:AWD 12-281
文献作者:H鰂gen,N.; Schupke,H.; Marx,D.; Gasparic,A.; Kronbach,T.; Hartenhauer,H.; Szelenyi,I.; Krone,D.; Hempel,R.; Kiss,H.; Berthold,K.; Egerland,U.; Olbrich,M.; Heer,S.; Rundfelt,C.
参考来源:Drugs Fut 2002,27(2),111