FS-32
Chemical Name: N,N-Dimethyl-N-[3-(5-methyl-3-phenyl-1H-indazol-1-yl)propyl]amine
项目整合开发状态: Biological Testing
项目研究机构: National Tsing Hua University (Originator)
合成路线:Alkylation of N,N-dimethyl-1,3-propanediamine (II) with ethyl bromoacetate (I) afforded the diamino ester (III).Basic hydrolysis of (III) and subsequent nitrosation of the resulting diamino acid (IV) yielded the nitrosamine (V).Cyclization of (V) in hot acetic anhydride as the dehydrating agent gave rise to sydnone (VI).Lithiation of (VI),followed by condensation with aldehyde (VII),produced adduct (VIII) as an inseparable mixture of diastereomers.The hydroxyl group of (VIII) was then protected as the methyl ether (IX) by alkylation with iodomethane and NaH.The azomethyne intermediate,generated by ejection of CO2 from (IX) upon heating in xylene,underwent an intramolecular 1,3-dipolar cycloaddition with the olefin double bond to furnish the indazole derivative (X).Finally,the target compound was obtained by aromatization of (X) under acidic conditions in the presence of platinum catalyst.
📌 参考资料/链接：
参考文献标题:An expedient synthesis of 1-[3-(dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS-32) - An antidepressant
文献作者:Yeu,J.P.; et al.
参考来源:Synthesis 2001,(12),1775
📄 详细内容
合成路线:It can be prepared in several different way (Scheme 31229302a):1) The nitrosation of 2-[3-(dimethylamino)propylamino]-5-methylbenzophenone (I) with NaNO2 and HCl in chloroform gives the corresponding N-nitroso compound (II),which is cyclized by reaction with Zn in acetic acid.2) By reaction of 1-(3-methylaminopropyl)-5-methyl-3-phenyl-1H-indazole (III) with formaldehyde and NaBH4 in methanol.3) The reaction of 3-phenyl-5-methyl-1H-indazole (IV) with 1,3-dibromopropane (V) by means of NaH in DMF gives 1-(3-bromopropyl)-5-methyl-3-phenyl-1H-indazole (VI),which is then condensed with dimethylamine (VII).4) By reaction of (IV) with 1-(dimethylamino)-3-bromopropane (VIII) by means of NaOH in a mixture of toluene and water.
参考文献标题:FS-32
文献作者:Blancafort,P.; Serradell,M.N.; Casta馿r,J.; Paton,D.M.
参考来源:Drugs Fut 1979,4(8),583
合成路线:It can be prepared in several different way (Scheme 31229302a):1) The nitrosation of 2-[3-(dimethylamino)propylamino]-5-methylbenzophenone (I) with NaNO2 and HCl in chloroform gives the corresponding N-nitroso compound (II),which is cyclized by reaction with Zn in acetic acid.2) By reaction of 1-(3-methylaminopropyl)-5-methyl-3-phenyl-1H-indazole (III) with formaldehyde and NaBH4 in methanol.3) The reaction of 3-phenyl-5-methyl-1H-indazole (IV) with 1,3-dibromopropane (V) by means of NaH in DMF gives 1-(3-bromopropyl)-5-methyl-3-phenyl-1H-indazole (VI),which is then condensed with dimethylamine (VII).4) By reaction of (IV) with 1-(dimethylamino)-3-bromopropane (VIII) by means of NaOH in a mixture of toluene and water.
参考文献标题:
文献作者:Fujimura,Y.; et al.(Chugai Pharmaceutical Co.Ltd.)
参考来源:JP 7714766
合成路线:It can be prepared in several different way (Scheme 31229302a):1) The nitrosation of 2-[3-(dimethylamino)propylamino]-5-methylbenzophenone (I) with NaNO2 and HCl in chloroform gives the corresponding N-nitroso compound (II),which is cyclized by reaction with Zn in acetic acid.2) By reaction of 1-(3-methylaminopropyl)-5-methyl-3-phenyl-1H-indazole (III) with formaldehyde and NaBH4 in methanol.3) The reaction of 3-phenyl-5-methyl-1H-indazole (IV) with 1,3-dibromopropane (V) by means of NaH in DMF gives 1-(3-bromopropyl)-5-methyl-3-phenyl-1H-indazole (VI),which is then condensed with dimethylamine (VII).4) By reaction of (IV) with 1-(dimethylamino)-3-bromopropane (VIII) by means of NaOH in a mixture of toluene and water.
参考文献标题:
文献作者:Fujimura,Y.; et al.(Chugai Pharmaceutical Co.Ltd.)
参考来源:JP 7659861
合成路线:It can be prepared in several different way (Scheme 31229302a):1) The nitrosation of 2-[3-(dimethylamino)propylamino]-5-methylbenzophenone (I) with NaNO2 and HCl in chloroform gives the corresponding N-nitroso compound (II),which is cyclized by reaction with Zn in acetic acid.2) By reaction of 1-(3-methylaminopropyl)-5-methyl-3-phenyl-1H-indazole (III) with formaldehyde and NaBH4 in methanol.3) The reaction of 3-phenyl-5-methyl-1H-indazole (IV) with 1,3-dibromopropane (V) by means of NaH in DMF gives 1-(3-bromopropyl)-5-methyl-3-phenyl-1H-indazole (VI),which is then condensed with dimethylamine (VII).4) By reaction of (IV) with 1-(dimethylamino)-3-bromopropane (VIII) by means of NaOH in a mixture of toluene and water.
参考文献标题:
文献作者:Fujimura,Y.; et al.(Chugai Pharmaceutical Co.Ltd.)
参考来源:JP 7714765
合成路线:It can be prepared in several different way (Scheme 31229302a):1) The nitrosation of 2-[3-(dimethylamino)propylamino]-5-methylbenzophenone (I) with NaNO2 and HCl in chloroform gives the corresponding N-nitroso compound (II),which is cyclized by reaction with Zn in acetic acid.2) By reaction of 1-(3-methylaminopropyl)-5-methyl-3-phenyl-1H-indazole (III) with formaldehyde and NaBH4 in methanol.3) The reaction of 3-phenyl-5-methyl-1H-indazole (IV) with 1,3-dibromopropane (V) by means of NaH in DMF gives 1-(3-bromopropyl)-5-methyl-3-phenyl-1H-indazole (VI),which is then condensed with dimethylamine (VII).4) By reaction of (IV) with 1-(dimethylamino)-3-bromopropane (VIII) by means of NaOH in a mixture of toluene and water.
参考文献标题:
文献作者:Fujimura,Y.; et al.(Chugai Pharmaceutical Co.Ltd.)
参考来源:DE 2503815; FR 2259601; GB 1489280; JP 75106958; JP 75145244; JP 75148335; JP 7663172; US 3994890
合成路线:It can be prepared in several different way (Scheme 31229302a):1) The nitrosation of 2-[3-(dimethylamino)propylamino]-5-methylbenzophenone (I) with NaNO2 and HCl in chloroform gives the corresponding N-nitroso compound (II),which is cyclized by reaction with Zn in acetic acid.2) By reaction of 1-(3-methylaminopropyl)-5-methyl-3-phenyl-1H-indazole (III) with formaldehyde and NaBH4 in methanol.3) The reaction of 3-phenyl-5-methyl-1H-indazole (IV) with 1,3-dibromopropane (V) by means of NaH in DMF gives 1-(3-bromopropyl)-5-methyl-3-phenyl-1H-indazole (VI),which is then condensed with dimethylamine (VII).4) By reaction of (IV) with 1-(dimethylamino)-3-bromopropane (VIII) by means of NaOH in a mixture of toluene and water.
参考文献标题:
文献作者:Fujimura,Y.; et al.(Cubist Pharmaceuticals,Inc.)
参考来源:JP 76125281