新产品编号:166619

Chemical Name: 2-[6-(4-Amidinobenzamido)-3,4-dihydro-2H-1-benzopyran-2-yl]acetic acid ethyl ester
CAS No. 181072-77-5, 181072-57-1 (hydrochloride)
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator)
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.