抗帕金森新药雷莎吉兰盐酸盐合成的改进

24220066()J.ofXuzhouNormalUniv.(NaturalScienceEdition)Vol.24,No.2Jun.,2006:2005211206:(JHB04-038):(1982-),,,,.,,(,221116):12,R212,32,.,,.:;;:R91415;R97115:A:100726573(2006)0220064203(Rasagiline)2B(MAO2B),TevaLundbeck,(Levodopa),,20052,FDA.(Selegiline),,,,[1].:1)3212,L2,,R2,[2];2),,,,[3];3)32,,[4].R212,[4],12,R212,32,.,,,.:1:X4,;6890A/5973NGC2MS;BrukerDpx2400;WZZ22B.:(CP,),(AR,),(AR,),,,,(AR,),,(AR,).111N2212(2)250ml2210g(0117mol)122010ml6010ml,0163g,4h,,10ml3,,,,.112N2212(3)215010ml,410g,24h,15ml10%.,30ml,,,,210220/10mmHg,3118g,:8411%([5]:82%).113(R2(+)2N2212)2L2(4)2215g(0115mol)(R,R)250010ml,75,2910g(0113mol)3,30min,10h1919g,1613g,:3316%.mp:136144,[]D=+514(c=115,CH3CH2OH)([5],mp:135144,[]D=+410(c=5134,CH3CH2OH)).1HNMR(DMSO):71257148(m,9H,ArH),4106(s,1H,CH),4102(s,2H,CH2),21093105(m,4H,2CH2).114R2(-)212(5)[6,7]1010g(0103mol)4,1010g5%Pd2C[6]10010ml,12atm50,24h,,6010ml,30%pH12,,,,,,,9095/10mmHg,314g,:8312%(9616%GC),[]D=-1519(c=217,CH3OH)([5],[]D=-16(c=217,CH3OH)).1.5R2(+)2N2212(6)216g(0102mol)5,217g,2010ml60,119g(01016mol)32,15h,,3010ml10%,,,,.,VV=46,,114g,:4019%.MaSs(EI):170(M+-1),132(M+-CH2CCH),117(M+-NHCH2CCH).1HNMR(CDCl3):71217139(m,4H,ArH),41454148(m,1H,CH),3156(s,2H,CH2),31053.12(m,1H,CH),1.882.90(m,4H,CH2),01991103(m,1H,CCH).1.6R2(+)2N2212(7)113g(716mmol)6,,,,1149g,:90%.mp:188190,[]D=+3017(c=2,C2H5OH)([3],mp:183185,[]D=+3019(c=2,C2H5OH)).1HNMR(CDCl3):71257178(m,4H,ArH),41914193(m,1H,CH),31633171(s,2H,CH2),21392159(m,4H,CH2),1170(s,1H,CCH).221132,.,562:23,.,,.,,.8411%([5]:82%).2124[5]43L2,48h.,,10h,10h,,3316%([5]:32%).21355,[5]25atm,,12atm,,,8312%([5]:72%).2146[4]32R2,32R212,,1018%.:[1].RasagilineMesilate[J].,2003,27(5):316.[2]TirtsahBP,Youdim2MoussaBH,RuthL,etal.R2enantinerofN2propargyl2l2aminoindan,salt,compositionsandusesthereof[P].WO:9511016,1955204227.[3],.[J].,2004,13(12):1354.[4]YoudimBH,FinbergPM,LevyRN,etal.R2enantiomersofN2propargyl212aminoindan,itspreparationandphar2maceuticalcompositionscontainingit[P].EP:0436492,1991207210.[5]GutmaAL,ZaltzmanI,PonomarevV,etal.ProcessforthepreparationofRasagilineanditssalts[P].WO:02068376,2002209206.[6].[M].:,1982:166-183.[7],,,.2,62[J].:,1999,17(2):31.TheImprovementoftheSynthesisofR2(+)2N2propargyl212aminoindanHydrochlorideLILei,ZHANGXue2mei,WANGYu2cheng(DepartmentofChemistry,XuzhouNormalUniversity,Xuzhou,Jiangsu,221116,China)Abstract:R2(+)2N2propargyl212aminoindanhydrochloride(i.e.Rasagiline,anewmedicineforcuringparkinsonism)wassynthesizedfrom12indanonebycondensation,reduction,resolution,cata2lytichydrogenation,etc..Thechemicalstructureofthetargetcompoundwasconfirmedbyassayofthemeltingpoint,NMR,MSandopticalactivity.Keywords:parkinsonism;Rasagiline;synthesis66()24