新产品编号:649129
Chemical Name: (?-N-[trans-4-(cis-1-allyl-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-ylaminomethyl)cyclohexylmethyl]benzenesulfonamide
CAS No. 247936-57-8
项目整合开发状态: Preclinical
项目研究机构: R.W. Johnson (Originator)
合成路线:Condensation of 4-fluorophenylacetyl chloride (I) with ethylene in the presence of AlCl3 provided the beta-tetralone (II).After conversion of (III) into enamine (IV) upon reaction with pyrrolidine (III) in MeOH,alkylation with allyl bromide (V) afforded iminium salt (VI).Acid hydrolysis of (VI) generated the allyl tetralone (VII),which was subjected to reductive amination with ammonium acetate and sodium cyanoborohydride to produce the cis-1-allyl-2-aminotetralin (VIII) as the major isomer.Coupling of (VIII) with carboxylic acid (IX) using 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) gave amide (X),which was finally reduced to the target aminotetralin derivative with LiAlH4.
📌 参考资料/链接：
参考文献标题:N-Substd.aminotetralins as ligands for the neuropeptide Y Y5 receptor useful in the treatment of obesity and other disorders
文献作者:Reitz,A.B.; Lovenberg,T.W.; Dax,S.L.; Youngman,M.A.; McNally,J.J.(Ortho-McNeil Pharmaceutical,Inc.)
参考来源:WO 9955667
📄 详细内容
合成路线:Condensation of 4-fluorophenylacetyl chloride (I) with ethylene in the presence of AlCl3 provided the beta-tetralone (II).After conversion of (III) into enamine (IV) upon reaction with pyrrolidine (III) in MeOH,alkylation with allyl bromide (V) afforded iminium salt (VI).Acid hydrolysis of (VI) generated the allyl tetralone (VII),which was subjected to reductive amination with ammonium acetate and sodium cyanoborohydride to produce the cis-1-allyl-2-aminotetralin (VIII) as the major isomer.Coupling of (VIII) with carboxylic acid (IX) using 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) gave amide (X),which was finally reduced to the target aminotetralin derivative with LiAlH4.
参考文献标题:alpha-Substituted N-(sulfonamido)alkyl-beta-aminotetralins: Potent and selective neuropeptide Y Y5 receptor antagonists
文献作者:Youngman,M.A.; McNally,J.J.; Lovenberg,T.W.; Reitz,A.B.; Willard,N.M.; Nepomuceno,D.H.; Wilson,S.J.; Crooke,J.J.; Rosenthal,D.; Vaidya,A.H.; Dax,S.L.
参考来源:J Med Chem 2000,43(3),346