Y-34867
3-喹喹羧酸,1-环丙基-7-[2-[(二甲基氨基)甲基]-4-甲基苯丙基]-6-氟-1,4-二氢-8-甲氧基-4-氧基-Chemical Name: (-)-1-Cyclopropyl-7-[2(S)-(dimethylaminomethyl)morpholin-4-yl]-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid
CAS No. 133762-22-8 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Mitsubishi Pharma (Originator)
合成路线:Condensation of epichlorohydrin (I) with N-benzylethanolamine (II) in the presence of sulfuric acid afforded the (chloromethyl)morpholine (III).Halogen displacement in (III) by potassium phthalimide (IV) provided the substituted phthalimide (V).Further hydrazinolysis of (V) furnished racemic (aminomethyl)morpholine (VI) (1).The desired (S) enantiomer (VII) was obtained by crystallization of (VI) as the dibenzoyl-D-tartaric acid salt,followed by liberation of the base with NaOH.Eschweiler-Clarke reductive methylation of (VII) with formaldehyde and formic acid produced the dimethylamino derivative (VIII).The N-benzyl groupof (VIII) was then cleaved by transfer hydrogenation in the presence of hydrazine and Pd/C yielding chiral morpholine (IX).Finally,coupling of this morpholine (IX) with the difluoroqyuinolone boron chelate (X) provided the title morpholino quinolone.
📌 参考资料/链接：
参考文献标题:Synthesis and anti-Helicobacter pylori activity of Y-34867,a new 7-morpholinoquinolone
文献作者:Uemori,S.; Hirayama,F.; Moriguchi,A.; Sano,M.; Yokoyama,Y.; Ikeda,Y.; Miyoshi,M.; Sakurai,N.; Yamamoto,K.; Kawakita,T.
参考来源:38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998,San Diego) 1998,Abst F-85
📄 详细内容
合成路线:Condensation of epichlorohydrin (I) with N-benzylethanolamine (II) in the presence of sulfuric acid afforded the (chloromethyl)morpholine (III).Halogen displacement in (III) by potassium phthalimide (IV) provided the substituted phthalimide (V).Further hydrazinolysis of (V) furnished racemic (aminomethyl)morpholine (VI) (1).The desired (S) enantiomer (VII) was obtained by crystallization of (VI) as the dibenzoyl-D-tartaric acid salt,followed by liberation of the base with NaOH.Eschweiler-Clarke reductive methylation of (VII) with formaldehyde and formic acid produced the dimethylamino derivative (VIII).The N-benzyl groupof (VIII) was then cleaved by transfer hydrogenation in the presence of hydrazine and Pd/C yielding chiral morpholine (IX).Finally,coupling of this morpholine (IX) with the difluoroqyuinolone boron chelate (X) provided the title morpholino quinolone.
参考文献标题:Synthesis and structure-activity relationships of 7-(2-aminoalkyl)morpholinoquinolones as anti-Helicobacter pylori agents
文献作者:Sakurai,N.; Sano,M.; Hirayama,F.; Kuroda,T.; Uemori,S.; Moriguchi,A.; Yamamoto,K.; Ikeda,Y.; Kawakita,T.
参考来源:Bioorg Med Chem Lett 1998,8(16),2185
产品链接: CAS No. 133762-22-8››