新产品编号:410247
Chemical Name: N-(2,2-Dimethylcyclopentylmethyl)-4-[5-(3,3,3-trifluoropropyl)-1,2,4-oxadiazol-3-yl]benzamide isomer A
CAS No. 212380-87-5 ((-)-enantiomer), 212380-88-6 ((+)-enantiomer)
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Treatment of 2,2-dimethylcyclopentanone (I) with tosylmethyl isocyanide and potassium tert-butoxide produced nitrile (II),which was reduced to amine (III) employing LiAlH4 in THF.Coupling of amine (III) with mono-methyl terephthalate (IV) by means of EDC and HOBt gave amide (V).The target oxadiazole system was then obtained by condensation of (V) with N-hydroxypentamidine (VI) in the presence of NaH,and the (S)-enantiomer was isolated by using chiral HPLC.
合成路线:Amine (III) was synthesized from 2,2-dimethylcyclopentanone (I) by treatment with tosylmethyl isocyanide,followed by reduction of the resultant nitrile (II) with LiAlH4.Condensation of 4-cyanobenzoic acid (IV) with amine (III) produced the corresponding amide (V).Subsequent addition of hydroxylamine to the cyano group of (V) gave rise to the hydroxyamidine (VI).The target oxadiazole derivative was then obtained by condensation of (VI) with 4,4,4-trifluorobutyric acid (VII),followed by cyclization under basic conditions.Separation of the enantiomers was carried out by chiral preparative HPLC.
📌 参考资料/链接：
参考文献标题:Benzoic acid derivs.and related cpds.as antiarrhythmic agents
文献作者:Poss,M.A.; Lloyd,J.; Rovnyak,G.C.; Caulfield,T.J.; Atwal,K.S.; Stein,P.D.; Ahmad,S.(Bristol-Myers Squibb Co.)
参考来源:WO 9837068
📄 详细内容
合成路线:Amine (III) was synthesized from 2,2-dimethylcyclopentanone (I) by treatment with tosylmethyl isocyanide,followed by reduction of the resultant nitrile (II) with LiAlH4.Condensation of 4-cyanobenzoic acid (IV) with amine (III) produced the corresponding amide (V).Subsequent addition of hydroxylamine to the cyano group of (V) gave rise to the hydroxyamidine (VI).The target oxadiazole derivative was then obtained by condensation of (VI) with 4,4,4-trifluorobutyric acid (VII),followed by cyclization under basic conditions.Separation of the enantiomers was carried out by chiral preparative HPLC.
参考文献标题:Design and synthesis of 4-substituted benzamides as potent,selective,and orally bioavailable IKS blockers
文献作者:LLoyd,J.; Schmidt,J.B.; Rovnyak,G.; Ahmad,S.; Atwal,K.S.; Bisaha,S.N.; Doweyko,L.M.; Stein,P.D.; Traeger,S.C.; Mathur,A.; Conder,M.L.; DiMarco,J.; Harper,T.W.; Jenkins-West,T.; Levesque,P.C.; Normandin,D.E.; Russell,A.D.; et al.
参考来源:J Med Chem 2001,44(23),3764