NNC-45-0781
(3S,4R)-3-苯基-4-[4-(2-吡咯利丁-1-二乙氧基)苯基]-3,4-二氢-2H-铬-7-醇Chemical Name: (-)-3(S)-Phenyl-4(R)-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-3,4-dihydro-2H-1-benzopyran-7-ol
CAS No. 207277-66-5
项目整合开发状态: Preclinical
项目研究机构: Novo Nordisk (Originator)
合成路线:Coumarin (III) was prepared by condensation of benzophenone (I) with phenylacetic acid (II) in the presence of Ac2O and Et3N.Reduction of the lactone function of (III) with LiAlH4,followed by acidic treatment furnished diaryl chromene (IV).Subsequent hydrogenation of (IV) over Pd/C gave rise to the racemic cis chromane (V),which was O-alkylated with 1-(2-chloroethyl) pyrrolidine (VI) producing the corresponding (pyrrolidinyl)ethoxy derivative.Resolution by means of active ditoluoyl tartaric acid yielded the desired (-)-enantiomer (VII).Finally,cleavage of the methoxy group using pyridine hydrochloride at 150 C provided the title compound.
📌 参考资料/链接：
参考文献标题:Novel (-)-enantiomers of cis-3,4-chroman derivs.useful in the prevention or treatment of estrogen related diseases or syndromes
文献作者:Jacobsen,P.; Treppendahl,S.; Stanley Bury,P.; Kanstrup,A.; Brown Christiansen,L.(Novo Nordisk A/S)
参考来源:EP 0937057; WO 9818771
📄 详细内容
合成路线:Coumarin (III) was prepared by condensation of benzophenone (I) with phenylacetic acid (II) in the presence of Ac2O and Et3N.Reduction of the lactone function of (III) with LiAlH4,followed by acidic treatment furnished diaryl chromene (IV).Subsequent hydrogenation of (IV) over Pd/C gave rise to the racemic cis chromane (V),which was O-alkylated with 1-(2-chloroethyl) pyrrolidine (VI) producing the corresponding (pyrrolidinyl)ethoxy derivative.Resolution by means of active ditoluoyl tartaric acid yielded the desired (-)-enantiomer (VII).Finally,cleavage of the methoxy group using pyridine hydrochloride at 150 C provided the title compound.
参考文献标题:Novel cis-3,4-chroman derivs.useful in the prevention or treatment of estrogen related diseases or syndromes
文献作者:Jacobsen,P.; Treppendahl,S.; Stanley Bury,P.; Kanstrup,A.; Brown Christiansen,L.(Novo Nordisk A/S)
参考来源:EP 0937060; WO 9818776
合成路线:Coumarin (III) was prepared by condensation of benzophenone (I) with phenylacetic acid (II) in the presence of Ac2O and Et3N.Reduction of the lactone function of (III) with LiAlH4,followed by acidic treatment furnished diaryl chromene (IV).Subsequent hydrogenation of (IV) over Pd/C gave rise to the racemic cis chromane (V),which was O-alkylated with 1-(2-chloroethyl) pyrrolidine (VI) producing the corresponding (pyrrolidinyl)ethoxy derivative.Resolution by means of active ditoluoyl tartaric acid yielded the desired (-)-enantiomer (VII).Finally,cleavage of the methoxy group using pyridine hydrochloride at 150 C provided the title compound.
参考文献标题:Synthesis and pharmacological evaluation of novel cis-3,4-diaryl-hydroxychromanes as high affinity partial agonists for the estrogen receptor
文献作者:Bury,P.S.; Christiansen,L.B.; Jacobsen,P.; Jorgensen,A.S.; Kanstrup,A.; Naerum,L.; Bain,S.; Fledelius,C.; Gissel,B.; Hansen,B.S.; Korsgaard,N.; Thorpe,S.M.; Wassermann,K.
参考来源:Bioorg Med Chem 2002,10(1),125
产品链接: CAS No. 207277-66-5››