A method of preparing a compound of the formula, wherein: n is 1, 2 or 3; m is 1; t is 0, 1 or 2; y is 1 or 2; z is 0, 1 or 2; E is O; X 1 is CR 1; X 2 is O; X 3 is -NH; X 4 is CR 4 R 5, CH 2 CR 4 R 5 or CH 2 -(C 1 -C 6) alkyl-CR 4 R 5; X 5 is a direct bond, O, S, SO 2, CR 4 R 5, (C 1 -C 6)alkyl, (C 1 -C 6)alkyloxy, (C 1 -C 6)alkenyl, (C 1 -C 6)alkenyloxy; R 1 is H, CN, (C 1 -C 6)alkylcarbonyl, or (C 1 -C 6)alkyl; R 4 and R 5 are independently selected from H, (C 1 -C 6)alkyl, or taken together with the carbon to which they are attached to form a spiro (C 3 -C 10)cycloalkyl ring or spiro (C 3 -C 10)cycloalkoxy ring; R 6 is -H, halogen, -CN, (C 6 -C 12)aryl, (C 6 -C 12)aryloxy, (C 1 -C 6)alkyloxy; (C 1 -C 6)alkyl optionally substituted by one to four halo or (C 1 -C 6)alkyl; A 1 is (C 2 -C 6)alkynyl; (C 3 -C 10)cycloalkyl, (C 6 -C 12)aryl, (C 2 -C 9)heteroaryl, (C 2 -C 9)heterocycloalkyl or benzo(C 2 -C 9)heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of halo, (C 1 -C 6)alkyl optionally substituted by one to three halo; (C 1 -C 6)alkenyl, amino, (C 1 -C 6)alkylamino, (C 1 -C 6)dialkylamino, (C 1 -C 6)alkoxy, nitro, CN, -OH, (C 1 -C 6)alkyloxy optionally substituted by one to three halo; (C 1 -C 6)alkoxycarbonyl, and (C 1 -C 6) alkylcarbonyl; A 2 is H, (C 3 -C 10)cycloalkyl, (C 6 -C 12)aryl, (C 2 -C 9)heteroaryl, (C 2 -C 9)heterocycloalkyl or benzo(C 2 -C 9)heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of halo, (C 1 -C 6)alkyl optionally substituted by one to three halo; (C 1 -C 6)alkylenyl, amino, (C 1 -C 6) alkylamino, (C 1 -C 6)dialkylamino, (C 1 -C 6)alkoxy, O(C3-C6 cycloalkyl), (C 3 -C 6) cycloalkoxy, nitro, CN, OH, (C 1 -C 6)alkyloxy optionally substituted by one to three halo; (C 3 -C 6) cycloalkyl, (C 1 -C 6) alkoxycarbonyl, (C 1 -C 6) alkylcarbonyl, (C 1 -C 6) haloalkyl; with the proviso that the sum of n + t + y + z is not greater than 6; comprising reacting the compound of Formula II and the compound of Formula IV with a compound of Formula III wherein n, t, y, z, X 4, A 1, X 5 and A 2 are as defined above, the method further including reacting, while heating to reflux, the compound of Formula V with imidazole to form the compounds of Formula II and Formula IV wherein X 4, A 1, X 5 and A 2 are as defined above. n is 1, 2 or 3; m is 1; t is 0, 1 or 2; y is 1 or 2; z is 0, 1 or 2; E is O; X 1 is CR 1; X 2 is O; X 3 is -NH; X 4 is CR 4 R 5, CH 2 CR 4 R 5 or CH 2 -(C 1 -C 6) alkyl-CR 4 R 5; X 5 is a direct bond, O, S, SO 2, CR 4 R 5, (C 1 -C 6)alkyl, (C 1 -C 6)alkyloxy, (C 1 -C 6)alkenyl, (C 1 -C 6)alkenyloxy; R 1 is H, CN, (C 1 -C 6)alkylcarbonyl, or (C 1 -C 6)alkyl; R 4 and R 5 are independently selected from H, (C 1 -C 6)alkyl, or taken together with the carbon to which they are attached to form a spiro (C 3 -C 10)cycloalkyl ring or spiro (C 3 -C 10)cycloalkoxy ring; R 6 is -H, halogen, -CN, (C 6 -C 12)aryl, (C 6 -C 12)aryloxy, (C 1 -C 6)alkyloxy; (C 1 -C 6)alkyl optionally substituted by one to four halo or (C 1 -C 6)alkyl; A 1 is (C 2 -C 6)alkynyl; (C 3 -C 10)cycloalkyl, (C 6 -C 12)aryl, (C 2 -C 9)heteroaryl, (C 2 -C 9)heterocycloalkyl or benzo(C 2 -C 9)heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of halo, (C 1 -C 6)alkyl optionally substituted by one to three halo; (C 1 -C 6)alkenyl, amino, (C 1 -C 6)alkylamino, (C 1 -C 6)dialkylamino, (C 1 -C 6)alkoxy, nitro, CN, -OH, (C 1 -C 6)alkyloxy optionally substituted by one to three halo; (C 1 -C 6)alkoxycarbonyl, and (C 1 -C 6) alkylcarbonyl; A 2 is H, (C 3 -C 10)cycloalkyl, (C 6 -C 12)aryl, (C 2 -C 9)heteroaryl, (C 2 -C 9)heterocycloalkyl or benzo(C 2 -C 9)heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of halo, (C 1 -C 6)alkyl optionally substituted by one to three halo; (C 1 -C 6)alkylenyl, amino, (C 1 -C 6) alkylamino, (C 1 -C 6)dialkylamino, (C 1 -C 6)alkoxy, O(C3-C6 cycloalkyl), (C 3 -C 6) cycloalkoxy, nitro, CN, OH, (C 1 -C 6)alkyloxy optionally substituted by one to three halo; (C 3 -C 6) cycloalkyl, (C 1 -C 6) alkoxycarbonyl, (C 1 -C 6) alkylcarbonyl, (C 1 -C 6) haloalkyl; with the proviso that the sum of n + t + y + z is not greater than 6;