新产品编号:1720143

合成路线:Tetralone (I) was reduced with NaBH4 and the resulting alcohol (II) was dehydrated with p-TsOH in refluxing toluene to yield the dihydronaphthalene (III).Oxidation of (III) with N-methylmorpholine N-oxide and OsO4 produced diol (IV),which was converted to the 2-tetralone (V) by acid-catalyzed rearrangement.The unstable tetralone (V) was condensed with the sodium salt of tert-butyl diethyl phosphonoacetate (VI) providing a mixture of olefin isomers (VII).Catalytic hydrogenation of the olefin (VIIa-c) with simultaneous removal of the carbobenzoxy group furnished the aminotetralin (VIII).This was coupled with 4-cyanobenzoic acid (IX) using EDC to give amide (X).Addition of H2S to the nitrile group of (X),followed by S-methylation provided (XI).Then,displacement of the methylthio group of (XI) by ammonium acetate and further treatment with di-tert-butyl dicarbonate yielded the Boc-protected benzamidine (XII).Deprotection with trifluoroacetic acid produced the amidino acid (XIII),which was finally esterified with EtOH and HCl.

参考文献标题:Glycoprotein IIb/IIIa antagonists
文献作者:Fisher,M.J.; Jakubowski,J.A.; Martinelli,M.J.; Morin,J.M.Jr.; Paal,M.; Ruhter,G.; Ruterbories,K.J.; Schotten,T.; Stenzel,W.; Vasileff,R.T.(Eli Lilly and Company)
参考来源:EP 0804431; JP 1999502194; WO 9622288


合成路线:Tetralone (I) was reduced with NaBH4 and the resulting alcohol (II) was dehydrated with p-TsOH in refluxing toluene to yield the dihydronaphthalene (III).Oxidation of (III) with N-methylmorpholine N-oxide and OsO4 produced diol (IV),which was converted to the 2-tetralone (V) by acid-catalyzed rearrangement.The unstable tetralone (V) was condensed with the sodium salt of tert-butyl diethyl phosphonoacetate (VI) providing a mixture of olefin isomers (VII).Catalytic hydrogenation of the olefin (VIIa-c) with simultaneous removal of the carbobenzoxy group furnished the aminotetralin (VIII).This was coupled with 4-cyanobenzoic acid (IX) using EDC to give amide (X).Addition of H2S to the nitrile group of (X),followed by S-methylation provided (XI).Then,displacement of the methylthio group of (XI) by ammonium acetate and further treatment with di-tert-butyl dicarbonate yielded the Boc-protected benzamidine (XII).Deprotection with trifluoroacetic acid produced the amidino acid (XIII),which was finally esterified with EtOH and HCl.

合成路线:Hydrogenation of 6-nitrocoumarin (I) in the presence of Pd/C and di-tert-butyl dicarbonate provided (II).Partial reduction of the lactone function of (II) with DIBAL at low temperature gave rise to lactol (III),which was submitted to a Wittig condensation with (ethoxycarbonyl)triphenylphosphorane (IV) yielding chromaneacetic acid ethyl ester (V).The Boc protecting group of (V) was then removed with trifluoroacetic acid to afford aniline (VI),which was acylated with 4-cyanobenzoic acid (VII) in the presence of EDC to give amide (VIII).Addition of H2S to the nitrile group of (VIII),followed by S-methylation provided (IX).Then,displacement of the methylthio group of (IX) by ammonium acetate and further treatment with di-tert-butyl dicarbonate yielded the Boc-protected benzamidine (X).Finally,Boc-deprotection with trifluoroacetic acid furnished the title amidino ester.
参考文献标题:Fused bicyclic Gly-Asp beta-turn mimics with specific affinity for GPIIb-IIIa
文献作者:Fisher,M.J.; Arfstan,A.E.; Giese,U.; Gunn,B.P.; Harms,C.S.; Khau,V.; Kinnick,M.D.; Lindstrom,T.D.; Martinelli,M.J.; Mest,H.J.; Mohr,M.; Morin,J.M.Jr.; Mullaney,J.T.; Nunes,A.; Paal,M.; Rapp,A.; Ruhter,G.; Ruterbories,K.J.; et al.
参考来源:J Med Chem 1999,42(23),4875