A78277, DPC-A78277
Chemical Name: 5(S)-(Cyclopropylmethoxy)-7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo[b]-1,8-naphthyridine 1-oxide
CAS No. 335448-58-3
项目整合开发状态: Discontinued
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The condensation of 2-chloropyridine (I) with ethyl trifluoroacetate (II) by means of LDA in THF gives 2-chloro-3-(trifluoroacetyl)pyridine (III),which is condensed with 4-fluoroaniline (IV) by means of refluxing aqueous acetic acid to yield the diarylamine (V).The cyclization of (V) by means of concentrated H2SO4 affords 7-fluoro-5-hydroxy-5-(trifluoromethyl)-5,10-dihydro-benzo[b]-1,8-naphthyridine (VI),which is dehydrated in THF to give 7-fluoro-5-(trifluoromethyl)benzo[b]-1,8-naphthyridine (VII).The condensation of (VII) with cyclopropylmethanol (VIII) by means of anhydrous HCl in dichloromethane yields the 5-(cyclopropylmethoxy)-7-fluoro-5-(trifluoromethyl)-5,10-dihydro-benzo[b]-1,8-naphthyridine (IX),which is oxidated by means of MCPBA in dichloromethane to afford the N-oxide (X) (1,2).Finally,this racemic compound is submitted to chiral HPLC to obtain the target enantiomer (1).
📌 参考资料/链接：
参考文献标题:Tricyclic cpds.useful as HIV reverse transcriptase inhibitors
文献作者:Patel,M.; Rodgers,J.D.; Wang,H.; Johnson,B.L.(Bristol-Myers Squibb Co.)
参考来源:JP 2003512375; US 6593337; WO 0129037
📄 详细内容
合成路线:The condensation of 2-chloropyridine (I) with ethyl trifluoroacetate (II) by means of LDA in THF gives 2-chloro-3-(trifluoroacetyl)pyridine (III),which is condensed with 4-fluoroaniline (IV) by means of refluxing aqueous acetic acid to yield the diarylamine (V).The cyclization of (V) by means of concentrated H2SO4 affords 7-fluoro-5-hydroxy-5-(trifluoromethyl)-5,10-dihydro-benzo[b]-1,8-naphthyridine (VI),which is dehydrated in THF to give 7-fluoro-5-(trifluoromethyl)benzo[b]-1,8-naphthyridine (VII).The condensation of (VII) with cyclopropylmethanol (VIII) by means of anhydrous HCl in dichloromethane yields the 5-(cyclopropylmethoxy)-7-fluoro-5-(trifluoromethyl)-5,10-dihydro-benzo[b]-1,8-naphthyridine (IX),which is oxidated by means of MCPBA in dichloromethane to afford the N-oxide (X) (1,2).Finally,this racemic compound is submitted to chiral HPLC to obtain the target enantiomer (1).
参考文献标题:Novel 5,10-dihydrobenzo[B][1,8]napthyridine N-oxides as non-nucleoside reverse transcriptase inhibitors of HIV-1 with high potency against clinically relevant mutants variants
文献作者:Johnson,B.L.; Tarby,C.M.; Srivastava,A.; Bakthavatchalam,R.; Lin,Q.; Cocuzza,A.J.; Bilder,D.M.; Bacheler,L.T.; Diamond,S.; Jeffrey,S.; Klabe,R.M.; Cordova,B.C.; Garber,S.; Logue,K.; Erickson-Viitanen,S.K.; Trainor,G.L.; et al.
参考来源:226th ACS Natl Meet (Sept 7 2003,New York) 2003,Abst MEDI 129