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Afloqualone, HQ-495, Arofuto

氟喹酮Chemical Name: 6-Amino-2-(fluoromethyl)-3-(2-methylphenyl)-4(3H)-quinazolinone
CAS No. 56287-74-2, 56287-75-3 (HCl)
项目整合开发状态: Launched-1983
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:1) The acylation of N-(2-amino-5-nitrobenzoyl)-o-toluidine (I) with fluoroacetyl chloride by means of pyridine in THF gives N-(2-fluoroacetamido-5-nitrobenzoyl)-o-toluidine (II),which is cyclized by means of refluxing acetic anhydride acetic acid to yield 6-nitro-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (III).Finally,this compound is reduced with H2 over Pd/C in acetic acid or with SnCl2 - HCl in methanol - water.2) The acylation of (I) with chloroacetyl chloride as before gives N-(2-chloroacetamido-5-nitro-benzoyl)-o-toluidine (IV),which is cyclized with acetic anhydride as before affording 6-nitro-2-chloromethyl-3-(o-tolyl)-4(3H)-quinazolinone (V).Finally,the treatment of (V) with KF in refluxing diethylene glycol yields (III).
📌 参考资料/链接:
参考文献标题:2-Fluoromethyl-3-o-tolyl-6-amino-4(3H)-quinazolinone
文献作者:Inoue,I.; Oine,T.; Yamada,Y.; Tani,J.; Ishida,R.; Ochiai,T.(Tanabe Seiyaku Co.,Ltd.)
参考来源:BE 0853031; CH 605831; DE 2449113; FR 2247246; GB 1476698; JP 50064283; US 3966731

📄 详细内容


合成路线:1) The acylation of N-(2-amino-5-nitrobenzoyl)-o-toluidine (I) with fluoroacetyl chloride by means of pyridine in THF gives N-(2-fluoroacetamido-5-nitrobenzoyl)-o-toluidine (II),which is cyclized by means of refluxing acetic anhydride acetic acid to yield 6-nitro-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (III).Finally,this compound is reduced with H2 over Pd/C in acetic acid or with SnCl2 - HCl in methanol - water.2) The acylation of (I) with chloroacetyl chloride as before gives N-(2-chloroacetamido-5-nitro-benzoyl)-o-toluidine (IV),which is cyclized with acetic anhydride as before affording 6-nitro-2-chloromethyl-3-(o-tolyl)-4(3H)-quinazolinone (V).Finally,the treatment of (V) with KF in refluxing diethylene glycol yields (III).

合成路线:3) The reduction of (V) with SnCl2 as before gives 6-amino-2-chloromethyl-3-(o-tolyl)-4(3H)-quinazolinone (VI),which is acylated with acetyl chloride as before to yield 6-acetamido-2-chloromethyl-3-(o-tolyl)-4(3H)-quinazolinone (VII).The treatment of (VII) with KF in diethylene glycol at 160 C yields 6-acetamido-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (VIII),which is finally deprotected by treatment with HCl in methanol.

参考文献标题:Afloqualone
文献作者:Castar,J.; Blancafort,P.; Serradell,M.N.; Sweetman,A.J.
参考来源:Drugs Fut 1982,7(8),539


合成路线:1) The acylation of N-(2-amino-5-nitrobenzoyl)-o-toluidine (I) with fluoroacetyl chloride by means of pyridine in THF gives N-(2-fluoroacetamido-5-nitrobenzoyl)-o-toluidine (II),which is cyclized by means of refluxing acetic anhydride acetic acid to yield 6-nitro-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (III).Finally,this compound is reduced with H2 over Pd/C in acetic acid or with SnCl2 - HCl in methanol - water.2) The acylation of (I) with chloroacetyl chloride as before gives N-(2-chloroacetamido-5-nitro-benzoyl)-o-toluidine (IV),which is cyclized with acetic anhydride as before affording 6-nitro-2-chloromethyl-3-(o-tolyl)-4(3H)-quinazolinone (V).Finally,the treatment of (V) with KF in refluxing diethylene glycol yields (III).

参考文献标题:
文献作者:Inoue,I.; Oine,T.; Yamada,Y.; Tani,J.
参考来源:JP 76105083


合成路线:3) The reduction of (V) with SnCl2 as before gives 6-amino-2-chloromethyl-3-(o-tolyl)-4(3H)-quinazolinone (VI),which is acylated with acetyl chloride as before to yield 6-acetamido-2-chloromethyl-3-(o-tolyl)-4(3H)-quinazolinone (VII).The treatment of (VII) with KF in diethylene glycol at 160 C yields 6-acetamido-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (VIII),which is finally deprotected by treatment with HCl in methanol.
参考文献标题:
文献作者:Inoue,I.; Oine,T.; Yamada,Y.; Tani,J.
参考来源:JP 76105082


产品链接: CAS No. 56287-74-2››

产品链接: CAS No.56287-75-3››