PREPARATION OF ASYMMETRIC CYCLIC UREAS THROUGH A MONOACYLATED DIAMINE INTERMEDIATE

摘要

The present invention concerns an improved process for the preparation of asymmetric cyclic ureas as well as intermediates in the preparation of asymmetric cyclic ureas of formula (VI): wherein: R7 is selected from the following: C1-C8 alkyl substituted with 0-3 R11; C2-C8 alkenyl substituted with 0-3 R11; C2-C8 alkynyl substituted with 0-3 R11; and a C3-C14 carbocyclic ring system substituted with 0-3 R11; R10 is C1-C10 alkyl, benzyl, naphthylmethyl, 3,4-methylenedioxybenzyl, or C1-C4 alkyl substituted with phenyl wherein said phenyl is substituted with 0-3 R10a; G taken together along with the oxygen atoms to which G is attached forms a group selected from: -O-C(-CH2CH2CH2CH2CH2-)-O-, -O-C(CH2CH3)2-O-, -O-C(CH3)(CH2CH3)-O-, -O-C(CH2CH2CH2CH3)2-O-, -O-C(CH3)(CH2CH(CH3)CH3)-O-, -O-CH(phenyl)-O-, OCH2O-, OC(CH3)2O- and -OC(OCH3)(CH2CH2CH3)O-. In the process, a diamine of formula (I a) is selectively monoacylated to give an asymmetric monoacylated diamine which can be converted into asymmetric intermediates. The asymmetric intermediates can be further alkylated, cyclized, and/or modified to give compounds which are useful as HIV protease inhibitors for the treatment of HIV infection. The invention allows for scalable preparation of a wide variety of asymmetrical cyclic ureas.