GMC2-83
11-(4-甲基-1-吡嗪基)二苯并[b,f][1,4]奥沙西平-2-yl Trifluo Ro甲烷磺酸fonateChemical Name: 11-(4-Methylpiperazin-1-yl)-2-(trifluoromethanesulfonyloxy)dibenzo[b,f][1,4]oxazepine
CAS No. 183140-98-9
项目整合开发状态: Preclinical
项目研究机构: Lundbeck (Originator), Merck KGaA (Originator)
合成路线:Condensation of 2-chloronitrobenzene (I) with 2-hydroxy-4-methoxybenzaldehyde (II) by means of Cu/KOH in refluxing DMF provides derivative (III),which is then oxidized with KMnO4 in pyridine/H2O to afford carboxylic acid (IV).Reduction of the nitro moiety of (IV) by hydrogenation over Pd/C yields amine (V),which is then cyclized at high temperatures to furnish the dibenzo[b,f][1,4]oxazepinone intermediate (VI) (1).O-Demethylation of (VI) by treatment with AlCl3 in ethylmercaptan (EtSH) gives hydroxy derivative (VII),which then reacts with triflic anhydride in CH2Cl2 in the presence of Et3N to provide compound (VIII).Treatment of (VIII) with POCl3 in refluxing toluene in the presence of N,N-dimethylaniline yields chloro derivative (IX),which is finally condensed with N-methylpiperazine (X) in refluxing toluene to give the desired product.
📌 参考资料/链接：
参考文献标题:New sulfone ester analogues of iso-clozapine and related structures: Atypical neuroleptics
文献作者:De Boer,P.; Liao,Y.; Wikstr鰉,H.
参考来源:WO 9629316
📄 详细内容
合成路线:Condensation of 2-chloronitrobenzene (I) with 2-hydroxy-4-methoxybenzaldehyde (II) by means of Cu/KOH in refluxing DMF provides derivative (III),which is then oxidized with KMnO4 in pyridine/H2O to afford carboxylic acid (IV).Reduction of the nitro moiety of (IV) by hydrogenation over Pd/C yields amine (V),which is then cyclized at high temperatures to furnish the dibenzo[b,f][1,4]oxazepinone intermediate (VI) (1).O-Demethylation of (VI) by treatment with AlCl3 in ethylmercaptan (EtSH) gives hydroxy derivative (VII),which then reacts with triflic anhydride in CH2Cl2 in the presence of Et3N to provide compound (VIII).Treatment of (VIII) with POCl3 in refluxing toluene in the presence of N,N-dimethylaniline yields chloro derivative (IX),which is finally condensed with N-methylpiperazine (X) in refluxing toluene to give the desired product.
参考文献标题:New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: Chemistry and pharmacological evaluation
文献作者:Liao,Y.; Venhuis,B.J.; Rodenhuis,N.; Timmerman,W.; Wikstr鰉,H.; Meier,E.; Bartoszyk,G.D.; Bottcher,H.; Seyfried,C.A.; Sundell,S.
参考来源:J Med Chem 1999,42(12),2235
产品链接: CAS No. 183140-98-9››