| 主权项 |
1. A process for the preparation of a compound of formula (I) wherein Ar2 is a monocyclic or bicyclic ring system, unsaturated, saturated or aromatic, optionally fused, optionally including between 1 and 5 heteroatom ring moieties independently selected from the group consisting of O, S, N, SO2 and C═O; wherein said Ar2 ring system is optionally substituted with between 1 and 4 substituents; W represents O, S, NR27, C═O, (C═O)NH, NH(C═O), CHR28, or a covalent bond; R27 is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, naphthyl, benzyl, phenethyl, C1-5heterocyclyl, C2-8acyl, aroyl, R29OC═O, R30R31NC═O, R29SO, R29S, R29SO2 or R30R31 NSO2; or alternatively, R27 and part of Ar2 can be taken together to form an optionally substituted 5- to 6-membered heterocyclic ring with optionally 1 to 3 additional heteroatom moieties in the ring selected from O, NR9, NR10, N, SO2, C═O and S; which ring may be saturated, unsaturated or aromatic; wherein R9 and R10 are independently selected from the group consisting of H, C1-3alkyl, and —CH2CO2(C1-4alkyl); R28 is hydrogen, C1-5alkyl, C3-5alkenyl, hydroxy, phenyl, benzyl, C1-5heterocyclyl, R29O, R30R31NC═O, R29S, R29SO, R29SO2 or R30R31NSO2; R29 is C1-5alkyl, C3-5alkenyl, phenyl, benzyl or C1-5heterocyclyl; R30 and R31 are each independently selected from the group consisting of hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, naphthyl, and C1-5heteroaryl; alternatively R30 and R31 can be taken together to form an optionally substituted 4- to 7-membered ring carbocyclic or heterocyclic ring, which ring may be saturated, unsaturated or aromatic; Rz is H or OH and the dashed line is absent; or Rz is absent where the dashed line is an sp2 bond; R5 and R6 are each independently selected from the group consisting of hydrogen and C1-5alkyl; n is an integer selected from 0, 1 or 2; R7 and R8 are each independently hydrogen, C1-5alkyl, C2-5alkenyl, C1-5alkoxy, C1-5alkylthio, halogen, or a 4-7 membered carbocyclyl or heterocyclyl; alternatively, R7 and R8 can be taken together to form an optionally substituted 5- to 7-membered carbocyclic or heterocyclic ring, which ring may be unsaturated or aromatic, and may be optionally substituted with between one and three substituents independently selected from the group consisting of halo, cyano, amino, hydroxy, nitro, R4, R4O—, R4S—, R4O(C1-5alkylene)-, R4O(C═O)—, R4(C═O)—, R4(C═S)—, R4(C═O)O—, R4O(C═O)(C═O)—, R4SO2, NHR44(C═NH)—, NHR44SO2—, an NHR44(C═O)—; R4 is H, C1-5alkyl, C2-5alkenyl, C1-5heterocyclyl, (C1-5heterocyclyl)C1-6alkylene, phenyl, benzyl, phenethyl, NH2, mono- or di(C1-6alkyl)N-, (C1-6alkoxy)carbonyl- or R42OR43—; wherein R42 is H, C1-5alkyl, C2-5alkenyl, phenyl, benzyl, phenethyl, C1-5heterocyclyl, or (C1-5heterocyclyl)C1-6alkylene- and R43 is C1-5alkylene, phenylene, or divalent C1-5heterocyclyl; R44 is H, C1-5alkyl, C2-5alkenyl, C1-5heterocyclyl, (C1-5heterocyclyl)C1-6alkylene, phenyl, benzyl, phenethyl, NH2, mono- or di(C1-6alkyl)N-, (C1-6alkoxy)carbonyl- or R42OR43—; wherein R42 is H, C1-5alkyl, C2-5alkenyl, phenyl, benzyl, phenethyl, C1-5heterocyclyl, or (C1-5heterocyclyl)C1-6alkylene- and R43 is C1-5alkylene, phenylene, or divalent C1-5heterocyclyl; Ar represents a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with between 1 and 3 substituents independently selected from the group consisting of halogen, C1-5alkoxy, C1-5alkyl, C2-5alkenyl, cyano, azido, nitro, R22R23N, R24SO2, R24SO, R24OC═O, R22R23NC═O, C1-5haloalkyl, C1-5haloalkoxy, C1-5haloalkylthio and C1-5alkylthio; R22 is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, phenethyl, benzyl, C1-5heterocyclyl, C2-8acyl, aroyl, R38OC═O, R25R26NC═O, R38SO, R38SO2, R38S, or R25R26NSO2; R23 is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl or C1-5heterocyclyl; alternatively, R22 and R23 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic; R24 is C1-5alkyl, C3-5alkenyl, phenyl, benzyl, or C1-5heterocyclyl; R25 and R26 independently are hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl or C1-5heterocyclyl; or alternatively, R25 and R26 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic; R38 is H, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl or C1-5heterocyclyl; wherein each of the above hydrocarbyl or heterocarbyl groups, unless otherwise indicated, and in addition to any specified substituents, is optionally and independently substituted with between 1 and 3 substituents selected from the group consisting of methyl, halomethyl, hydroxymethyl, halo, hydroxy, amino, nitro, cyano, C1-5alkyl, C1-5alkoxy, —COOH, C2-6acyl, [di(C1-4alkyl)amino]C2-5alkylene, [di(C1-4alkyl)amino]C2-5alkyl-NH—CO—, and C1-5haloalkoxy; or a pharmaceutically acceptable salt, amide or ester thereof; or a stereoisomeric form thereof; comprising reacting a compound of formula (V) with a compound of formula (VI), wherein LG1 is a leaving group; in the presence of an organic or inorganic base; to yield the corresponding compound of formula (VII); reacting the compound of formula (VII) with a compound of formula (X); in an organic solvent; to yield the corresponding compound of formula (I). |
