Patent ID: 8686141
Filing Date: 2014-04-01
Classification: A61P,C07D,Y02P

Abstract:
1. A process for preparing a compound of Formula I: which comprises: (A) contacting a compound of Formula II: with an acylating agent of Formula III: in an aprotic organic solvent and in the presence of base to obtain an acylated amine compound of Formula IV: and (B) contacting the compound of Formula IV with an aqueous base in an aprotic organic solvent to obtain the compound of Formula I; wherein: X is halogen or OC(O)R 6 ; R 1 is C 1-6 alkyl or C 1-6 alkyl substituted with AryA; R 2 is C 1-8 alkyl or AryB; R 3 is H or C 1-6 alkyl; R 4 is C 1-6 alkyl substituted with AryC; AryC is phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted with from 1 to 4 substituents each of which is independently: (1) C (2) C (3) C (4) O—C (5) O—C (6) O—C (7) S—C (8) S—C (9) S—C (10) halo, (11) CN, (12) NO (13) N(H)R (14) N(—C (15) CH(O), (16) C(O)—C (17) C(O)O—C (18) C(O)NH (19) C(O)N(H)—C (20) C(O)N(—C (21) C (22) AryQ, with the proviso that no more than one of the optional substituents is AryQ; AryA independently has the same definition as AryC; AryB independently has the same definition as AryC; L is C 1-6 alkylene; R 5 is H or C 1-6 alkyl; R 6 is: (1) HetP, (2) C (3) C(O)—C (4) C(O)—HetP, (5) CycQ, (6) O-CycQ, (7) C(O)-CycQ, (8) C(O)O-CycQ, (9) AryQ, (10) O-AryQ, (11) C(O)-AryQ, (12) C(O)O-AryQ, (13) HetQ, (14) O-HetQ, (15) C(O)—HetQ, or (16) C(O)O-HetQ; R E is a branched C 3-6 alkyl; HetP is a 4- to 7-membered saturated or mono-unsaturated heterocyclic ring containing 1 N atom through which the ring is attached to the rest of the compound and optionally containing an additional heteroatom wherein the additional heteroatom is selected from N, O, and S; wherein the optional S in the ring is optionally in the form of S(O) or S(O) 2 and the optional N in the ring is substituted with C 1-6 alkyl, C(O)—C 1-6 alkyl, or C(O)O—C 1-6 alkyl when the ring is saturated and is part of the ring double bond when the ring is mono-unsaturated; CycQ is a C 3-7 cycloalkyl which is optionally substituted with from 1 to 3 substituents each of which is independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, O—C 1-6 alkyl, O—C 1-6 haloalkyl, oxo, N(C 1-6 alkyl) 2 , C(O)N(C 1-6 alkyl) 2 , C(O)—C 1-6 alkyl, or C(O)O—C 1-6 alkyl; each AryQ is independently phenyl which is optionally substituted with from 1 to 4 substituents each of which is independently halogen, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, O—C 1-6 alkyl, O—C 1-6 haloalkyl, S—C 1-6 alkyl, N(C 1-6 alkyl) 2 , C(O)N(C 1-6 alkyl) 2 , C(O)—C 1-6 alkyl, or C(O)O—C 1-6 alkyl; and HetQ is a heteroaryl which is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from N, O and S, to which is optionally fused a benzene ring; wherein the heteroaryl is optionally substituted with from 1 to 4 substituents each of which is independently halogen, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, O—C 1-6 alkyl, O—C 1-6 haloalkyl, S—C 1-6 alkyl, N(—C 1-6 alkyl) 2 , C(O)N(—C 1-6 alkyl) 2 , C(O)—C 1-6 alkyl, or C(O)O—C 1-6 alkyl.