GYKI-46903
Chemical Name: (+)-endo-6-(4-Fluorophenyl)-4-(propionyloxy)-1-azabicyclo[3.3.1]non-6-ene hydrochloride; (+)-(4R*,5S*)-6-(4-Fluorophenyl)-4-(propionyloxy)-1-azabicyclo[3.3.1]non-6-ene hydrochloride
项目整合开发状态: Preclinical
项目研究机构: Institute for Drug Research (Originator)
合成路线:N-Benzyl-4-piperidone (I) was reacted with a Grignard reagent prepared from 4-fluorobromobenzene (II) to give the carbinol (III).The benzyl group was removed by catalytic hydrogenation and the resulting amine (IV) was alkylated with 3-bromopropionaldehyde ethylene acetal (V) to the alcohol (VI).Ring closure in hydrochloric acid gave the bicyclic endo-alcohol [(?-VII] along with some of the exo-isomer removed by crystallization.[(?-VII] was resolved by crystallization with (R,R)-tartaric acid mono-4-chloroanilide (VIII) to give [(+)-VII] of yet unknown absolute configuration.The latter was acylated with propionic anhydride followed by crystallization with hydrogen chloride in ether to furnish the end product.
📌 参考资料/链接：
参考文献标题:New 1-azabicycloalkane derivs.,pharmaceutical compsns.containing them and process for preparing same
文献作者:S髄yom,S.; Abraham,G.; Sz鰈sy,M.; Borsi,J.; Vit醠is,B.; Karimn?Tapfer,M.; Szab�?Bady,E.; Csuzdi,E.; Goldschmidtn?Horv醫h,K.; M�? G.; Ling,I.; Mikl髎n?Kov醕s,A.(Gyogyszerkutato Intezet Kft.)
参考来源:EP 0556342; JP 1994505706; WO 9207854
📄 详细内容
合成路线:N-Benzyl-4-piperidone (I) was reacted with a Grignard reagent prepared from 4-fluorobromobenzene (II) to give the carbinol (III).The benzyl group was removed by catalytic hydrogenation and the resulting amine (IV) was alkylated with 3-bromopropionaldehyde ethylene acetal (V) to the alcohol (VI).Ring closure in hydrochloric acid gave the bicyclic endo-alcohol [(?-VII] along with some of the exo-isomer removed by crystallization.[(?-VII] was resolved by crystallization with (R,R)-tartaric acid mono-4-chloroanilide (VIII) to give [(+)-VII] of yet unknown absolute configuration.The latter was acylated with propionic anhydride followed by crystallization with hydrogen chloride in ether to furnish the end product.
参考文献标题:GYKI-46903
文献作者:N骻r醖i,M.
参考来源:Drugs Fut 1993,18(5),421