文档介绍:【药物名称】Atorvastatincalcium,YM-548,CI-981,Prevencor,Tahor,Lipibec,Torvast,Sortis,Lipitor【化学名】(3R,5R)-7-[2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-yl]-3,5-dihydroxyheptanoicacidcalciumsalt(2:1)【CAS登记号】134523-03-8,134523-00-5(freeacid),110862-48-1(freeacid(R*,R*)-isomer)【结构式】2-C33-H34-F-N2-【分子量】【原研厂家】Jouveinal(Originator),Pfizer(Originator),AlmirallProdesfarma(Licensee),Syncro(Licensee),Yamanouchi(Licensee),StanfordUniversity(Codevelopment)【作用类别】Alzheimer'sDementia,Treatmentof,CARDIOVASCULADRUGS,CognitionDisorders,Treatmentof,euromuscularDisorders,Treatmentof,LipoproteinDisorders,Treatmentof,METABOLICDRUGS,MultipleSclerosis,Agentsfor,NEUROLOGICDRUGS,TreatmentofDisordersoftheCoronaryArteriesandAtherosclerosis,HMG-CoAReductaseInhibitors,TNFSF6ExpressionInhibitors【研发状态】Launched-1997【合成情况】NB2K来源】DrugsFutK合成路线』2欢is下载NH_II)CHaHCI2)BuaB1)NaOHHaOHCad,1)overnight2)crystaHizatjonAtorvastatinCalciumK合成方法】(II)bymeans1)Thecondensationof2-(1,3-dixolan-2-yl)ethylamine(I)withethyl2-bromo-2-(4-fluorophenyl)acetateoftriethylamineinacetonitrilegivesethyl2-[2-(1,3-dioxolan-2-yl)ethylamino]-2-(4-fluorophenyl)acetate(III),whichisacylatedwithisobutyrylchloride(IV)andtriethylamineindichloromethaneyieldingthecorrespondingamide(V).Saponificationoftheester(V)withNaOHinmethanol/wateraffordsthefreeacid(VI),whichiscyclizedwithN,3-diphenylpropynamide(VII)[obtainedinthereactionof3-phenylpropynoicacid(VIII)withaniline(IX)bymeansofdicyclohexylcarbodiimide(DCC)]byheatingat90Cinaceticanhydridegiving(X).Thehydrolysis1-[2-(1,3-dioxolan-2-yl)ethyl]-5-(4-fluorophenyl)-2-isopropyl-N,4-diphenylpyrrole-3-carboxamideofthedioxolanegroupof(X)withHClyieldsthecorrespondingaldehyde(XI),whichiscondensedwithmethylacetoacetate(XII)bymeansofNaHinTHFaffording7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(N-phenylcarbamoyl)pyrrol-1-yl]-5-hydroxy-3-oxoheptanoicacidmethylester(XIII).Thereductionofthecarbonylgroupof(XIII)withtributylboraneandNaBH4inTHFgivesthe(3R*,5R*)-dihydroxyester(XIV),