AS-1404, DMXAA, 5,6-MeXAA, NSC-640488
2,5-己酮可可碱Chemical Name: 5,6-Dimethyl-9-oxoxanthene-4-acetic acid
CAS No. 117570-53-3
项目整合开发状态: Phase I
项目研究机构: University of Auckland (Originator), Antisoma (Licensee), Roche (Licensee), Cancer Research UK (Codevelopment)
合成路线:The reaction of 2,3-dimethylaniline (I) with chloral hydrate (II) and hydroxylamine in hot aq.HCl gives the isonitrosoacetanilide (III),which is cyclized by means of hot Ms-OH or H2SO4 to yield 6,7-dimethylisatin (IV).The hydrolysis of (IV) by means of KOH and H2O2 in water affords 2-amino-3,4-dimethylbenzoic acid (V),which is diazotized with NaNO2 and H2SO4 and treated with KI to provide 2-iodo-3,4-dimethylbenzoic acid (VI).The condensation of (VI) with the sodium salt of 2-(2-hydroxyphenyl)acetic acid (VII) by means of tris[2-(2-methoxyethoxy)ethyl]amine (TDA) and CuCl in DMSO gives the precursor (VIII),which is finally cyclized by means of hot conc.aq.H2SO4 to furnish the target xanthene derivative.
📌 参考资料/链接：
参考文献标题:Cpds.having antitumour and antibacterial properties
文献作者:Denny,W.A.; Baguley,B.C.; Atwell,G.J.; Rewcastle,G.W.(Cancer Research UK; Pfizer Inc.)
参考来源:EP 0278176; US 5281620
📄 详细内容
合成路线:The reaction of 2,3-dimethylaniline (I) with chloral hydrate (II) and hydroxylamine in hot aq.HCl gives the isonitrosoacetanilide (III),which is cyclized by means of hot Ms-OH or H2SO4 to yield 6,7-dimethylisatin (IV).The hydrolysis of (IV) by means of KOH and H2O2 in water affords 2-amino-3,4-dimethylbenzoic acid (V),which is diazotized with NaNO2 and H2SO4 and treated with KI to provide 2-iodo-3,4-dimethylbenzoic acid (VI).The condensation of (VI) with the sodium salt of 2-(2-hydroxyphenyl)acetic acid (VII) by means of tris[2-(2-methoxyethoxy)ethyl]amine (TDA) and CuCl in DMSO gives the precursor (VIII),which is finally cyclized by means of hot conc.aq.H2SO4 to furnish the target xanthene derivative.
参考文献标题:Potential antitumor agents.61.Structure-activity relationships for in vivo colon 38 activity among disubstituted 9-oxo-9H-xanthene-4-acetic acids
文献作者:Rewcastle,G.W.; Atwell,G.J.; Li,Z.A.; Baguley,B.C.; Denny,W.A.
参考来源:J Med Chem 1991,34(1),217
合成路线:The reaction of 2,3-dimethylaniline (I) with chloral hydrate (II) and hydroxylamine in hot aq.HCl gives the isonitrosoacetanilide (III),which is cyclized by means of hot Ms-OH or H2SO4 to yield 6,7-dimethylisatin (IV).The hydrolysis of (IV) by means of KOH and H2O2 in water affords 2-amino-3,4-dimethylbenzoic acid (V),which is diazotized with NaNO2 and H2SO4 and treated with KI to provide 2-iodo-3,4-dimethylbenzoic acid (VI).The condensation of (VI) with the sodium salt of 2-(2-hydroxyphenyl)acetic acid (VII) by means of tris[2-(2-methoxyethoxy)ethyl]amine (TDA) and CuCl in DMSO gives the precursor (VIII),which is finally cyclized by means of hot conc.aq.H2SO4 to furnish the target xanthene derivative.
参考文献标题:An improved synthesis of 5,6-dimethylxanthenone-4-acetic acid (DMXAA)
文献作者:Atwell,G.J.; Yang,S.; Denny,W.A.
参考来源:Eur J Med Chem 2002,37(10),825
产品链接: CAS No. 117570-53-3››