新产品编号:52715
Chemical Name: 1-Ethyl-7-[3-[4-(4-fluorophenyl)-1-piperazinyl]propyl]-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione 4-oxime
CAS No. 150159-63-0
项目整合开发状态: Preclinical
项目研究机构: Daiichi Suntory Pharma (Originator)
合成路线:Treatment of methyl pyrrole-2-carboxylate (I) with KOtBu and 18-crown-6 in Et2O,followed by reaction with ethyl iodide (II) in Et2O,yields methyl 1-ethylpyrrole-2-carboxylate (III),which is then subjected to saponification with NaOH to afford carboxylic acid (IV).Condensation of (IV) with beta-alanine benzyl ester p-toluene sulfonate (V) in the presence of diethyl phosphorocyanidate (DEPC) and Et3N in DMF provides benzyl ester (VI),which is then hydrogenated over Pd/C in THF,furnishing carboxylic acid (VII).Cyclization of (VII) with polyphosphoric acid (PPA) affords derivative (VIII),which is then treated with NaH in DMF and alkylated with chloro derivative (IX) in DMF to produce compound (X).Finally,treatment of (X) with hydroxylamine hydrochloride and NaOAc affords the target compound.
📌 参考资料/链接：
参考文献标题:Pyrroloazepine cpd.
文献作者:Mizuno,A.; Miya,M.; Inomata,N.; Tatsuoka,T.; Ishihara,T.(Suntory Ltd.)
参考来源:EP 0557526; JP 1993503481; US 5399557; WO 9303032
📄 详细内容
合成路线:Treatment of methyl pyrrole-2-carboxylate (I) with KOtBu and 18-crown-6 in Et2O,followed by reaction with ethyl iodide (II) in Et2O,yields methyl 1-ethylpyrrole-2-carboxylate (III),which is then subjected to saponification with NaOH to afford carboxylic acid (IV).Condensation of (IV) with beta-alanine benzyl ester p-toluene sulfonate (V) in the presence of diethyl phosphorocyanidate (DEPC) and Et3N in DMF provides benzyl ester (VI),which is then hydrogenated over Pd/C in THF,furnishing carboxylic acid (VII).Cyclization of (VII) with polyphosphoric acid (PPA) affords derivative (VIII),which is then treated with NaH in DMF and alkylated with chloro derivative (IX) in DMF to produce compound (X).Finally,treatment of (X) with hydroxylamine hydrochloride and NaOAc affords the target compound.
参考文献标题:Studies on antihypertensive agents with antithrombotic activity.2.Syntheses and pharmacological evaluation of pyrrolo[2,3-c]azepine derivatives
文献作者:Mizuno,A.; Miya,M.; Kamei,T.; Shibata,M.; Tatsuoka,T.; Nakanishi,K.; Takiguchi,C.; Hidaka,T.; Yamaki,A.; Inomata,N.
参考来源:Chem Pharm Bull 2000,48(8),1129