摘要 |
<p>A synthesis is described for intermediates which are readily amenable to the large scale preparation of hydroxyethylurea-based chiral HIV protease inhibitors. The method includes forming a diastereoselective epoxide compound of formula (I) from a chiral alpha amino aldehyde and halomethyllithium as an organometallic methylene-adding reagent. In formula (I) R<1> is selected from alkyl, aryl, cycloalkyl, cycloalkylalkyl and arylalkyl, which are optionally substituted with a group selected from alkyl, halogen, NO2, OR<9> or SR<9>, where R<9> represents hydrogen or alkyl; and P<1> and P<2> independently are selected from amine protecting groups, including but not limited to, arylalkyl, substituted arylalkyl, cycloalkenylalkyl and substituted cycloalkenylalkyl, allyl, substituted allyl, acyl, alkoxycarbonyl, aralkoxycarbonyl and silyl.</p> |
申请人 |
G.D. SEARLE & CO., CHICAGO, ILL., US;MONSANTO CO., ST. LOUIS, MO., US |
发明人 |
NG, JOHN, S., CHICAGO, IL 60616, US;PRZYBYLA, CLAIRE, A., DES PLAINES, IL 60016, US;MUELLER, RICHARD, A., GLENCO, IL 60022, US;VAZQUEZ, MICHAEL, L., GURNEE, IL 60031, US;GETMAN, DANIEL, P., CHESTERFIELD, MO 63017, US |