Benzene, Pyridine, and Pyridazine Derivatives

A compound which is:

• 4-Amino-2-(4-hydroxy-cyclohexylamino)-benzonitrile;
• 3,6,6-trimethyl-6,7-dihydro-1H-benzo[d]imidazole-2,4(3H,5H)-dione;
• 6,6-dimethyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydro-1H-benzo[d]imidazole-2,4(3H,5H)-dione;
• 3,6,6-trimethyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydro-1H-benzo[d]imidazole-2,4(3H,5H)-dione;
• 3,6,6-trimethyl-6,7-dihydro-1H-benzo[d]imidazole-2,4(3H,5H)-dione;
• 6,6-dimethyl-7,7a-dihydro-1H-indole-2,4(5H,6H)-dione;
• or
• pharmaceutically acceptable salts thereof.

A process for preparing a compound of the formula F1

• wherein
• p is an integer greater than or equal to 1, and
• n is 0, 1, 2, 3, or 4,
• comprising
• (a) reacting a nitrile of formula F2 with an anhydride of Formula F3 and a compound of formula F4
• to provide a compound of formula F5
• (b) reducing a carboxylic acid of formula F5 to provide a compound of formula F6
• (c) treating a compound of formula F6 with 4-aminocyclohexanol to provide a compound of formula F7
• and (d) oxidizing the nitrile group of formula F7.

A process for preparing a compound of the formula F10:

• where
• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, wherein
• each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO′)2, —C(O)Ro, —C(O)ORO′, or —C(O)N(RO′)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO, —C(O)RO′, —C(O)ORO, or —C(O)N(RO′)2,
• wherein RO′ is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• the process comprising
• (a) converting a compound of formula F8
• to the corresponding hydroxyaminomethyl compound and
• (b) reacting the hydroxyaminomethyl compound with a diketocyclohexane derivative of formula F9
• to yield a compound of formula F11
• (c) cyclizing the compound of formula F11 to a benzimidazole-2,4(3H,5H)-dione of formula F12
• (d) alkylating the benzimidazole-2,4(3H,5H)-dione with a compound of the formula RN—X (formula F13a) or (RN)2-0 (formula F13b) to yield a compound of formula F14
• (e) removing the trimethoxybenzyl protecting group.

A process for preparing a compound of formula F15

• wherein
• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, wherein
• each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO′)2, —C(O)Ro, —C(O)ORO′, or —C(O)N(RO′)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO′, —C(O)RO′, —C(O)ORO′, or —C(O)N(RO′)2,
• wherein RO′ is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• R3 and R4 are independently (a) hydrogen, (b) halo, or (c) a C1-C15 alkyl group where up to six of the carbon atoms in said alkyl group are optionally replaced independently by R22, carbonyl, ethenyl, ethynyl or a moiety selected from N, O, or S(O)m, with the proviso that two O atoms, two S atoms, or an O and S atom are not immediately adjacent each other, wherein
• each (c) is optionally substituted with —RC, —OR15, —SR15, —N(R15)2, or —R22,
• each R15 is independently —H, (C1-C10)alkyl, (C1-C10)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C1-C10)alkyl-Z, wherein
• Z is —ORO or —N(R30)2, wherein
• each R30 is independently —H or C1-C6 alkyl;
• or N(R30)2 represents pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, 1,3- or 1,4-diazepanyl, or morpholinyl, each of which is optionally substituted with R;
• or R3 and R4 together with the atoms to which they are attached form a 5-12 membered mono-, bi-, or tricyclic ring system fused to the ring containing Q1 and Q2, where the 5-12 membered ring is partially unsaturated or aromatic and optionally contains one or two of oxygen, S(O)m, nitrogen, or NR33 where R33 is hydrogen or C1-C6 alkyl,
• the process comprising
• (a) reacting a compound formula F10
• with a nitrile of formula F16

A process for preparing a compound of formula F17

• wherein
• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, wherein
• each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO′)2, —C(O)RO, —C(O)ORO′, or —C(O)N(RO′)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO′, —C(O)RO′, —C(O)ORO′, or —C(O)N(RO′)2,
• wherein RO is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• R3 and R4 are independently (a) hydrogen, (b) halo, or (c) a C1-C15 alkyl group where up to six of the carbon atoms in said alkyl group are optionally replaced independently by R22, carbonyl, ethenyl, ethynyl or a moiety selected from N, O, or S(O)m, with the proviso that two O atoms, two S atoms, or an O and S atom are not immediately adjacent each other, wherein
• each (c) is optionally substituted with —RC, —OR15, —SR15, —N(R15)2, or —R22,
• each R15 is independently —H, (C1-C10)alkyl, (C1-C10)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C1-C10)alkyl-Z, wherein
• Z is —ORO or —N(R30)2, wherein
• each R30 is independently —H or C1-C6 alkyl;
• or N(R30)2 represents pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, 1,3- or 1,4-diazepanyl, or morpholinyl, each of which is optionally substituted with R;
• or R3 and R4 together with the atoms to which they are attached form a 5-12 membered mono-, bi-, or tricyclic ring system fused to the ring containing Q1 and Q2, where the 5-12 membered ring is partially unsaturated or aromatic and optionally contains one or two of oxygen, S(O)m, nitrogen, or NR33 where R33 is hydrogen or C1-C6 alkyl,
• the process comprising oxidizing the nitrile group of formula F15

A process for preparing a compound of formula F18

• wherein
• RC is independently halogen, cyano, nitro, —ORO, —N(RN)2, —S(O)mRN′, —S(O)mN(RN′)2, or —RN;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, where each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, and
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO)2, —C(O)RO, —C(O)ORO′, or —C(O)N(RO)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO′, —C(O)RO′, —C(O)ORO, or —C(O)N(RO)2,
• wherein RO is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• and
• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring,
• the process comprising
• (a) alkylating a diketone of formula F9 with an α-bromoacetate of formula F19 to yield to yield an ester of formula F20
• cyclizing the ester using an ammonium salt.

A process for preparing a compound of Formula F21

• wherein
• R3 and R4 are independently (a) hydrogen, (b) halo, or (c) a C1-C15 alkyl group where up to six of the carbon atoms in said alkyl group are optionally replaced independently by R22, carbonyl, ethenyl, ethynyl or a moiety selected from N, O, or S(O)m, with the proviso that two O atoms, two S atoms, or an O and S atom are not immediately adjacent each other, wherein
• each (c) is optionally substituted with —RC, —OR15, —SR15, —N(R15)2, or —R22,
• each R15 is independently —H, (C1-C10)alkyl, (C1-C10)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C1-C10)alkyl-Z, wherein
• Z is —ORO or —N(R30)2, wherein
• each R30 is independently —H or C1-C6 alkyl;
• or N(R30)2 represents pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, 1,3- or 1,4-diazepanyl, or morpholinyl, each of which is optionally substituted with R;
• or R3 and R4 together with the atoms to which they are attached form a 5-12 membered mono-, bi-, or tricyclic ring system fused to the ring containing Q1 and Q2, where the 5-12 membered ring is partially unsaturated or aromatic and optionally contains one or two of oxygen, S(O)m, nitrogen, or NR33 where R33 is hydrogen or C1-C6 alkyl;
• RC is independently halogen, cyano, nitro, —ORO, —N(RN)2, —S(O)mRN′, —S(O)mN(RN′)2, or —RN;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, where each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, and
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO′)2, —C(O)RO′, —C(O)ORO′, or —C(O)N(RO′)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO′, —C(O)RO′, —C(O)ORO′, or —C(O)N(RO′)2,
• wherein RO′ is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• and
• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring;
• R groups,
• the process comprising reacting a compound of formula F18 with a nitrile of formula F16

A process for preparing a compound formula F22

• wherein
• R21 is —C(O)OH, —C(O)—O(C1-C6alkyl), or —C(X)N(R11)2, wherein each R111 is independently hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, heteroaryl, aryl, C3-C8 cycloalkyl, heterocycloalkyl, wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide;
• or both R111 together with the nitrogen to which they are both attached, form a heterocycloalkyl;
• and
• X is ═O, ═S, ═NH, ═NOH, ═N—NH2, ═N—NHaryl, ═N—NH— (C1-C6 alkyl), or ═N— (C1-C6 alkoxy);
• R3 and R4 are independently (a) hydrogen, (b) halo, or (c) a C1-C15 alkyl group where up to six of the carbon atoms in said alkyl group are optionally replaced independently by R22, carbonyl, ethenyl, ethynyl or a moiety selected from N, O, or S(O)m, with the proviso that two O atoms, two S atoms, or an O and S atom are not immediately adjacent each other, wherein
• each (c) is optionally substituted with —RC, —OR15, —SR15, —N(R15)2, or —R22,
• each R15 is independently —H, (C1-C10)alkyl, (C1-C10)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C1-C10)alkyl-Z, wherein
• Z is —ORO or —N(R30)2, wherein
• each R30 is independently —H or C1-C6 alkyl;
• or N(R30)2 represents pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, 1,3- or 1,4-diazepanyl, or morpholinyl, each of which is optionally substituted with R;
• or R3 and R4 together with the atoms to which they are attached form a 5-12 membered mono-, bi-, or tricyclic ring system fused to the ring containing Q1 and Q2, where the 5-12 membered ring is partially unsaturated or aromatic and optionally contains one or two of oxygen, S(O)m, nitrogen, or NR33 where R33 is hydrogen or C1-C6 alkyl;
• RC is independently halogen, cyano, nitro, —ORO, —N(RN)2, —S(O)mRN′, —S(O)mN(RN′)2, or —RN;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, where each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, and
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO′)2, —C(O)Ro, —C(O)ORO′, or —C(O)N(RO′)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO, —C(O)RO′, —C(O)ORO, or —C(O)N(RO′)2,
• wherein RO′ is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• and
• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring;
• R groups,
• the process comprising oxidizing the nitrile group of a compound of formula F21

A process for preparing a compound of Formula F21

• wherein
• R3 and R4 are independently (a) hydrogen, (b) halo, or (c) a C1-C15 alkyl group where up to six of the carbon atoms in said alkyl group are optionally replaced independently by R22, carbonyl, ethenyl, ethynyl or a moiety selected from N, O, or S(O)m, with the proviso that two O atoms, two S atoms, or an O and S atom are not immediately adjacent each other, wherein
• each (c) is optionally substituted with —RC, —OR15, —SR15, —N(R15)2, or —R22,
• each R15 is independently —H, (C1-C10)alkyl, (C1-C10)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C1-C10)alkyl-Z, wherein
• Z is —ORO or —N(R30)2, wherein
• each R30 is independently —H or C1-C6 alkyl;
• or N(R30)2 represents pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, 1,3- or 1,4-diazepanyl, or morpholinyl, each of which is optionally substituted with R;
• or R3 and R4 together with the atoms to which they are attached form a 5-12 membered mono-, bi-, or tricyclic ring system fused to the ring containing Q1 and Q2, where the 5-12 membered ring is partially unsaturated or aromatic and optionally contains one or two of oxygen, S(O)m, nitrogen, or NR33 where R33 is hydrogen or C1-C6 alkyl;
• RC is independently halogen, cyano, nitro, —ORO, —N(RN)2, S(O)mRN′, —S(O)mN(RN′)2, or —RN;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, where each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, and
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO′)2, —C(O)Ro, —C(O)ORO′, or —C(O)N(RO′)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO′, —C(O)RO′, —C(O)ORO′, or —C(O)N(RO′)2,
• wherein RO′ is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• and
• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring;
• R groups,
• the process comprising reacting a compound of formula F18 with an amine of formula F23

A compound of the formula

• wherein
• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, wherein
• each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO′)2, —C(O)RO, —C(O)ORO, or —C(O)N(RO′)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO, —C(O)RO′, —C(O)ORO, or —C(O)N(RO′)2,
• wherein RO is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

A compound of the formula:

• R5 and R6 are independently H, C1-C6 alkyl, or aryl, wherein the aryl is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6)alkylamino, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, or carboxamide, wherein any two adjacent substituted aryl positions, together with the carbon atoms to which they are attached, optionally form an unsaturated cycloalkyl or heterocycloalkyl;
• or R5 and R6 taken together, on the same carbon and together with the carbon to which they are attached, form a 3-8 membered ring;
• RN is —RN′, —C(O)RN′, —C(O)ORN′, —C(O)N(RN′)2, —S(O)RN′, —S(O)2RN′, wherein
• each RN′ is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein
• each RN′ is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, halogen, cyano, nitro, halo(C1-C6)alkyl, heterocycloalkyl, aryl, or heteroaryl, —ORO, —N(RO′)2, —C(O)Ro, —C(O)ORO′, or —C(O)N(RO′)2, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 R groups;
• each RO is independently —RO′, —C(O)RO′, —C(O)ORO′, or —C(O)N(RO′)2,
• wherein RO′ is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each RO′ is optionally substituted with 1 to 4 R groups;
• and
• each R is independently halogen, cyano, nitro, C1-C6 alkyl, halo(C1-C6)alkyl, hydroxy, C1-C6 alkoxy, halo(C1-C6)alkoxy, amino, mono- or di-(C1-C6)alkylamino, carboxy, carboxamide, C3-C7 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.