Angiotensin II antagonists

A process of preparing a substantially pure (R) enantiomer of the compound of the formula:

• ##STR52## wherein:
• R.sub.1 is CO.sub.2 H, SO.sub.3 H, PO.sub.3 H.sub.2, CONHSO.sub.2 R.sub.5 or 5-tetrazolyl;
• R.sub.2 is H, --OH, --OCOCH.sub.3, halo, C.sub.1 -C.sub.4 alkyl, amino, acetamido, or C.sub.1 -C.sub.4 alkoxy;
• x is --(CH.sub.2).sub.m NHCO--, --(CH.sub.2).sub.m CONH--, --O--, --NH--, --CH.sub.2 --, --(CH.sub.2).sub.m CO--, or --CO(CH.sub.2).sub.m --;
• R.sub.3 is C.sub.4 -C.sub.9 straight chain alkyl, C.sub.4 -C.sub.9 straight chain trifluoroalkyl, C.sub.4 -C.sub.9 straight chain alkenyl, or C.sub.4 -C.sub.9 straight chain trifluoroalkenyl;
• R.sub.4 is --CONH(C.sub.1 -C.sub.4 alkyl), --CONH(C.sub.1 -C.sub.4 trifluoroalkyl), --CONH(hydroxy-C.sub.1 -C.sub.4 alkyl), ##STR53## R.sub.5 is phenyl, C.sub.1 -C.sub.4 alkyl substituted phenyl, C.sub.1 -C.sub.5 alkyl, or C.sub.1 -C.sub.5 trifluoroalkyl:
• R.sub.6 is (CH.sub.2).sub.p R.sub.1, or C.sub.1 -C.sub.4 alkyl;
• R.sub.7 is H or CH.sub.3 ;
• R.sub.8 is H or --(CH.sub.2).sub.q R.sub.12 ;
• R.sub.9 is O or S;
• R.sub.10 is H, --(CH.sub.2).sub.p R.sub.1, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 trifluoroalkyl, halo, substituted or unsubstituted phenyl, 3-pyridyl, 2pyrimidyl, furanyl, oxazolyl, isoxazolyl, a substituted or unsubstituted fused bicyclic, a substituted or unsubstituted fused tricyclic, or when m is 0, 4,4-ethylenedioxy;
• R.sub.11 is H, OH, C.sub.1 -C.sub.4 alkoxy, CO.sub.2 H, SO.sub.3 H, PO.sub.3 H.sub.2, CONHSO.sub.2 R.sub.5, or tetrazolyl;
• R.sub.12 is OH, NH.sub.2, or CO.sub.2 H:
• Y is a R group of a naturallyoccurring amino acid;
• X' is --O--, --(CH.sub.2).sub.p --, or --S--;
• m is independently 0 or 1;
• p is independently 0, 1, 2, 3 or 4;
• and
• q is 1, 2, 3, or 4:
• providing that when R.sub.4 is (g) or (h), and R.sub.10 is not H, the carboxy of (h) or tetrazolyl of (g) is in position 2;
• and when R.sub.4 is (g) or (h), m is 0, and R.sub.10 is H, the carboxy of (g) or tetrazolyl of (h) is in position 2 or 3;
• comprising
• coupling a compound of the formula (XXI) ##STR54## wherein R.sub.3 is C.sub.4 -C.sub.9 straight chain alkyl, C.sub.4 -C.sub.9 straight chain trifluoroalkyl, C.sub.4 -C.sub.9 straight chain alkenyl, or C.sub.4 -C.sub.9 straight chain trifluoroalkenyl;
• to a compound of the formula:
• ##STR55## wherein R.sub.6 is (CH.sub.2).sub.p R.sub.1, or C.sub.1 -C.sub.4 alkyl;
• R.sub.7 is H or CH.sub.3 ;
• R.sub.8 is H or --(CH.sub.2).sub.q R.sub.12 ;
• R.sub.9 is O or S;
• R.sub.10 is H, --(CH.sub.2).sub.p R.sub.1, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 trifluoroalkyl, halo, substituted or unsubstituted phenyl, 3-pyridyl, 2-pyrimidyl, furanyl, oxazolyl, isoxazolyl, a substituted or unsubstituted fused bicyclic, a substituted or unsubstituted fused tricyclic, or when m is 0, 4,4-ethylenedioxy;
• R.sub.11 is H, OH, C.sub.1 -C.sub.4 alkoxy, CO.sub.2 H, SO.sub.3 H, PO.sub.3 H.sub.2, CONHSO.sub.2 R.sub.5, or tetrazolyl;
• R.sub.12 is OH, NH.sub.2, or CO.sub.2 H;
• Y is a R group of a naturally occurring amino acid;
• providing that when R.sub.4 is (g) or (h), and R.sub.10 is not H, the carboxy of (h) or tetrazolyl of (g) is in position 2;
• and when R.sub.4 is (g) or (h), m is 0, and R.sub.10 is H, the carboxy of (g) or tetrazolyl of (h) is in position 2 or 3;
• reducing the nitro of the compound of the formula (XXI) to produce an amino imidazole;
• coupling the amino imidazole to a compound of the formula:
• ##STR56## wherein R.sub.2 is H, --OH, --OCOCH.sub.3, --halo, C.sub.1 -C.sub.4 alkyl, amino, acetamido, or C.sub.1 -C.sub.4 alkoxy, R.sub.1 is CO.sub.2 H, SO.sub.3 H, PO.sub.3 H.sub.2, CONHSO.sub.2 R.sub.5 or 5-tetrazolyl, R.sub.18 is SO.sub.2 or C.dbd.O.