Processes and intermediates for the preparation of cyclic urea HIV protease inhibitors

The compounds of the formulae:

• ##STR20## wherein:
• R.sup.1 and R.sup.2 are independently selected from the group:
• C.sub.1 -C.sub.4 alkyl, acetyl, phenyl;
• or R.sup.1 and R.sup.2 may be taken together to form a ring such as triazole, 4-methylpiperazine, or morpholine;
• R.sup.4 and R.sup.7 are independently selected from the group:
• hydrogen;
• C.sub.1 -C.sub.8 alkyl substituted with 0-3 R.sup.11 ;
• C.sub.3 -C.sub.14 carbocyclic ring system substituted with 0-3 R.sup.11 or 0-3 R.sup.12 ;
• a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R.sup.12 ;
• R.sup.11 and R.sup.11A are independently selected at each occurrence from the group:
• H, --CH.sub.2 NR.sup.13 R.sup.14, --NR.sup.13 R.sup.14, --OR.sup.13, --S(O).sub.m R.sup.13, --NR.sup.14 SO.sub.2 NR.sup.13 R.sup.14, --NR.sup.14 SO.sub.2 R.sup.13, --SO.sub.2 NR.sup.13 R.sup.14, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C.sub.7 -C.sub.10 arylalkyl, boronic acid, C.sub.3 -C.sub.6 cycloalkoxy, C.sub.1 -C.sub.4 alkyl substituted with --NR.sup.13 R.sup.14, C.sub.1 -C.sub.4 hydroxyalkyl, methylenedioxy, ethylenedioxy, 2-(1-morpholino)ethoxy, azido;
• C.sub.3 -C.sub.10 cycloalkyl substituted with 0-2 R.sup.12 ;
• C.sub.1 -C.sub.4 alkyl substitued with 0-2 R.sup.12 ;
• aryl(C.sub.1 -C.sub.3 alkyl)-, substituted with 0-2 R.sup.12 ;
• C.sub.2 -C.sub.6 alkoxyalkyl-, substituted with 0-2 R.sup.12 ;
• C.sub.5 -C.sub.14 carbocyclic residue substituted with 0-3 R.sup.12 ;
• a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-3 R.sup.12 ;
• R.sup.12, when a substituent on carbon, is independently selected at each occurrence from the group:
• phenyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, C.sub.7 -C.sub.10 arylalkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.6 cycloalkoxy, --OR.sup.13, C.sub.1 -C.sub.4 alkyl substituted with --NR.sup.13 R.sup.14, --NR.sup.13 R.sup.14, C.sub.2 -C.sub.6 alkoxyalkylene optionally substituted with --Si(CH.sub.3).sub.3, methylenedioxy, ethylenedioxy, --S(O).sub.m R.sup.13, --SO.sub.2 NR.sup.13 R.sup.14, --NHSO.sub.2 R.sup.14, 2-(1-morpholino)ethoxy;
• or
• a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur;
• or R.sup.12 may be a 3- or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6-membered ring being optionally substituted on the aliphatic carbons with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy;
• or
• --NR.sup.13 R.sup.14 ;
• or
• when R.sup.12 is attached to sulfur it may be .dbd.O;
• R.sup.12, when a substituent on nitrogen, is independently selected at each occurrence from the group:
• phenyl, benzyl, phenethyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, --CH.sub.2 NR.sup.13 R.sup.14, --NR.sup.13 R.sup.14, C.sub.2 -C.sub.6 alkoxyalkyl;
• R.sup.13 is independently selected at each occurrence from the group:
• H;
• phenyl substituted with 0-3 R.sup.11A ;
• benzyl substituted with 0-3 R.sup.11A ;
• C.sub.1 -C.sub.6 alkyl substituted with 0-3 R.sup.11A ;
• an amine protecting group when R.sup.13 is bonded to N;
• a hydroxy protecting group when R.sup.13 is bonded to O;
• R.sup.14 is independently selected at each occurrence from the group:
• hydrogen, hydroxy, C.sub.1 -C.sub.6 alkyl substituted with 0-3 groups selected from OH, C.sub.1 -C.sub.4 alkoxy, NH.sub.2, --NH(C.sub.1 -C.sub.4 alkyl), C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 alkenyl, phenyl, benzyl, an amine protecting group when R.sup.14 is bonded to N, a hydroxy protecting group when R.sup.14 is bonded to O;
• R.sup.13 and R.sup.14 can alternatively join to form --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 --, --CH.sub.2 CH.sub.2 N(R.sup.15)CH.sub.2 CH.sub.2 --, or --CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 --;
• R.sup.13A and R.sup.14A are independently selected at each occurrence from the group:
• H, C.sub.1 -C.sub.6 alkyl;
• R.sup.13A and R.sup.14A can alternatively join to form --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 --, --CH.sub.2 CH.sub.2 N(R.sup.15)CH.sub.2 CH.sub.2 --, or --CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 --;
• R.sup.15 is H or CH.sub.3.