Method of preparing therapeutic amides

A method of preparing an amide of the formula

• comprising the step of reacting a compound of the formula ##STR3## with an acid of the formula ##STR4## wherein E is selected from nitrogen and CZ wherein C is a ring carbon and Z is a substituent defined below, wherein:
• when E is CZ, X and Z are selected from the group consisting of:
• (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of:
• phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted;
• six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms;
• five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur;
• provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl, 3-(1-4C)alkylphenyl, or 4-pyridyl when Y is carbonyl, and that Ar is not 5-pyrimidinyl when Y is sulfonyl or carbonyl;
• and
• Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy;
• (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro, (1-4C)alkyl, and (1-4C)alkoxy;
• when E is nitrogen, X is independently selected from any of the values for X given above in (A);
• R.sup.2 and R.sup.3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R.sup.2 and R.sup.3 are not both methyl;
• or
• together, with the carbon atom to which both R.sup.2 and R.sup.3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.