Patent ID: 6399784
Filing Date: 2002-06-04
Classification: A61P,C07D,C07F

Abstract:
A process for the preparation of compound (I) or a pharmaceutically acceptable salt form thereof,said process comprising:(a) heating a compound of the formula (IV): wherein:R1 is selected from H or NHR1a; R1a is selected from the group consisting of: â€”C(&boxH;O)â€”Oâ€”R1b, â€”C(&boxH;O)â€”R1b, â€”C(&boxH;O)N(R1b)2, â€”C(&boxH;O)NHSO2R1b, â€”C(&boxH;O)NHC(&boxH;O)R1b, â€”C(&boxH;O)NHC(&boxH;O)OR1b, â€”C(&boxH;O)NHSO2NHR1b, â€”C(&boxH;S)â€”NHâ€”R1b, â€”NHâ€”C(&boxH;O)â€”Oâ€”R1b, â€”NHâ€”C(&boxH;O)R1b, â€”NHâ€”C(&boxH;)â€”NHâ€”R1b, â€”SO2â€”Oâ€”R1b, â€”SO2â€”R1b, â€”SO2â€”N(R1b)2, â€”SO2â€”NHC(&boxH;O)OR1b, â€”P(&boxH;S)(OR1b)2, â€”P(&boxH;O)(OR1b)2, â€”P(&boxH;S)(R1b)2, â€”P(&boxH;O)(R1b)2, and R1b is selected from the group consisting of: C1-C8 alkyl substituted with 0-2 R1c, C2-C8 alkenyl substituted with 0-2 R1c, C2-C8 alkynyl substituted with 0-2 R1c, C3-C8 cycloalkyl substituted with 0-2 R1c, aryl substituted with 0-4 R1c, aryl(C1-C6 alkyl)-substituted with 0-4 R1c, a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R1c, and C1-C6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4R1c; R1c is H, halogen, CF3, CN, NO2, C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylalkyl, aryl, aryl(C1-C6 alkyl)-, C1-C6 alkoxy, and C2-C5 alkoxycarbonyl; R2 is selected from H or C1-C10 alkyl; R3 and R4 are independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and aryl substituted with 0-2 R3a; R3a is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, CF3, NO2, and NR3bR3c; R3b and R3c are each independently selected from the group consisting of H, C1-C10 alkyl, C2-C10 alkoxycarbonyl, C2-C10 alkylcarbonyl, C1-C10 alkylsulfonyl, heteroaryl(C1-C4 alkyl)sulfonyl, aryl(C1-C10 alkyl)sulfonyl, arylsulfonyl, aryl, heteroarylcarbonyl, heteroarylsulfonyl, and heteroarylalkylcarbonyl, wherein said aryl and heteroaryl are optionally substituted with 0-3 R3d; R3d is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, CF3, and NO2; R5 is selected from the group consisting of: hydroxy, C1-C10 alkyloxy, C3-C11 cycloalkyloxy, C6-C10 aryloxy, C7-C11 arylalkyloxy, C3-C10 alkylcarbonyloxyalkyloxy, C3-C10 alkoxycarbonyloxyalkyloxy, C3-C10 alkoxycarbonylalkyloxy, C5-C10 cycloalkylcarbonyloxyalkyloxy, C5-C10 cycloalkoxycarbonyloxyalkyloxy, C5-C10 cycloalkoxycarbonylalkyloxy, C8-C11 aryloxycarbonylalkyloxy, C8-C12 aryloxycarbonyloxyalkyloxy, C8-C12 arylcarbonyloxyalkyloxy, C5-C10 alkoxyalkylcarbonyloxyalkyloxy, 5-(C5-C10 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)-methyloxy, (5-aryl-1,3dioxa-cyclopenten-2-one-yl)-methyloxy, and (R5a)HNâ€”(C1-C10 alkoxy)-; R5a is selected from the group consisting of H, C1-C4 alkyl, aryl(C1-C10 alkoxy)carbonyl, C2-C10 alkoxycarbonyl, and C3-C6 alkenyl; R6 is selected from the group consisting of H, CF3, CF2CF3, CF2CF2CF3, CF2CF2CF2CF3, C1-C8 alkyl, C1-C8 perfluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C11 cycloalkyl, C4-C11 cycloalkylalkyl, aryl(C1-C6 alkyl)-, C1-C6 alkoxy, C7-C10 arylalkyloxy, aryloxy and aryl substituted with 0-5 R6c; R6c is selected from the group consisting of H, halo, CF3, CN, NO2, NR6dR6e, C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylalkyl, aryl, aryl(C1-C6 alkyl)-, C1-C6 alkoxy, and C2-C5 alkoxycarbonyl; R6d and R6e are independently selected from the group consisting of H, C1-C10 alkyl, C2-C10 alkoxycarbonyl, C2-C10 alkylcarbonyl, C1-C10 alkylsulfonyl, aryl, aryl(C1-C10 alkyl)sulfonyl, arylsulfonyl, heteroaryl(C1-C4 alkyl)sulfonyl, heteroarylcarbonyl, heteroarylsulfonyl, or heteroarylalkylcarbonyl, wherein said aryl and heteroaryl are optionally substituted with 0-3 substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, CF3, and NO2; n is 0-4; a is a single or double bond, with the proviso that if a is a double bond, it is not simultaneously substituted with R3 and R4; for a time sufficient, and to a temperature sufficient to form a compound of formula (V): and;(b) reacting said compound of formula (V) with hydrogen under a suitable pressure in the presence of a hydrogenation catalyst to form a compound of formula (I) or a salt thereof.