<p>The present invention provides a process for preparing N<2>-[1(S)-ethoxycarbonyl-3-phenylpropyl]-N<6>-trifluoroacetyl-L-lysine and lisinopril thereof. Lisinopril shows excellent angiotensin converting enzyme inhibitor activity. Friedel-Crafts acylation of benzene with maleic anhydride in the presence of AlCl3 affords trans- beta -benzoylacrylic acid. Treatment of benzoylacrylic acid with HCl gas in ethanol gives ethyl 2-chloro-4-oxo-4-phenylbutyrate in high yield. The coupling reaction between ethyl 2-chloro-4-oxo-4-phenylbutyrate and trifluoroacetyl-L-lysine benzyl ester in the presence of a base pair and sodium iodide produces alkyl lydine derivative with a good diastereoselectivity. Catalytic hydrogenation of lysine derivative with palladium gives N<2>-[1(S)-ethoxycarbonyl-3-phenylpropyl]-N<6>-trifluoroacetyl-L-lysine. This intermediate is activated to form cyclic N-anhydride by using N,N-carbonyldiimidazole and coupled with L-proline methyl ester hydrochloride to give fully protected lisinopril derivative, which is converted into crude lisinopril by hydrolysis.</p>
申请公布号
WO2004000874(A1)
申请公布日期
2003.12.31
申请号
WO2002TR00023
申请日期
2002.06.19
申请人
EOS ECZACIBASI OZGUN KIMYASAL URUNLER SANYI VE TI;ASLAN, TUNCER;SAHBAZ, FILIZ;OZARSLAN, A. EVREN;YURDAKUL, AYCIL;RIDVANOGLU, NURTEN
发明人
ASLAN, TUNCER;SAHBAZ, FILIZ;OZARSLAN, A. EVREN;YURDAKUL, AYCIL;RIDVANOGLU, NURTEN