Substituted triazoles as angiotensin II inhibitors

The process for preparing a compound of the formula:

• ##STR10## wherein R.sub.1 is selected from H,C.sub.1-10 alkyl, C.sub.2-10 alkenyl, benzyl, substituted benzyl, (wherein the substitutent is selected from the group consisting of C.sub.1-5 alkyl, NO.sub.2, chloro, bromo, fluoro and iodo) phenyl, phenylalkenyl and substituted phenyl;
• (wherein the substitutent is selected from the group consisting of C.sub.1-5 alkyl, NO.sub.2, chloro, bromo, fluoro and iodo)
• R.sub.2 and R.sub.3 are the same or different and are selected from CO.sub.2 H, CO.sub.2 C.sub.1-5 alkyl, CN, CONH.sub.2, CONHOH, CON(R.sub.4).sub.2 and CONR.sub.4 OH wherein R.sub.4 is C.sub.1-5 alkyl;
• CONHR.sub.4 wherein R.sub.4 is 5-tetrazolo and X is S;
• Which comprises reacting one equivalent of a substituted mercaptotriazole of the formula:
• ##STR11## with two equivalents of a biphenylyl halide of the formula:
• ##STR12## wherein R.sub.2, R.sub.3 is CO.sub.2 C.sub.1-6 alkyl or CN and Z is Cl, Br, or I,
• in the presence of two equivalents of a base to form a mixture of compounds of the formula:
• ##STR13## and separating the products formed.

The process for preparing a compound of the formula:

• ##STR14## wherein R.sub.1 is selected from H, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, benzyl, substituted benzyl, (whereinthe substituent is slected from the group consisting of C.sub.1-5 alkyl, NO.sub.2, chloro, bromo, fluoroand iodo) phenyl, phenylalkenyl and substituted phenyl;
• (whereinthe substituent is slected from the group consisting of C.sub.1-5 alkyl, NO.sub.2, chloro, bromo, fluoro and iodo)
• R.sub.2 and R.sub.3 are the same or different and are selected from CO.sub.2 H, C0.sub.2 C.sub.1-6 alkyl, CN, CONH.sub.2, CONHOH, CON(R.sub.4).sub.2 and CONR.sub.4 OH wherein R.sub.4 is C.sub.1-6 alkyl;
• CONHR.sub.4 wherein R.sub.4 is 5-tetrazolo and X is SO or SO.sub.2 ;
• which comprises reacting a substituted mercaptotdazole of the formula:
• ##STR15## with two equivalents of a biphenylyl halide of the formula:
• ##STR16## wherein R.sub.2, R.sub.3 is CO.sub.2 C.sub.1-6 alkyl or CN and Z is CI, Br, or I in the presence of two equivalents of a base to form compounds of the formula:
• ##STR17## and:
• A, where X is SO,
• reacting the products formed with one equivalent of an oxidizing agent;
• and
• B, where X is SO.sub.2,
• reacting the products formed with two equivalents of an oxidizing agent;
• and separating the products formed,
• C, where R.sub.2 and/or R.sub.3 are CO.sub.2 H,
• reacting either product with a hydrolyzing agent and isolating the product,
• D, where R.sub.2 and R.sub.3 are the same or different and are selected from CONH.sub.2, CONHOH, COH(R.sub.4).sub.2 and CONR.sub.4 OH wherein R.sub.4 is C.sub.1-5 alkyl;
• CONHR.sub.4 wherein R.sub.4 is 5-tetrazolo,
• reacting the product of claim 7 C, with a chlodnating agent to generate the acid chloride COCl, and adding this acid chloride to a solution of the amine in the presence of a base.