PROCESS FOR PREPARING BICYCLIC COMPOUNDS

摘要

The present invention relates to a novel process for preparing compounds of formula (IA), which are potent and specific antagonists of corticotropin-releasing factor (CRF) receptors, from intermediate compounds of formula (I), by a coupling reaction catalysed by copper (I) (Ia)wherein R is aryl or heteroaryl, each of which may be substituted by 1 to 4 groups selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, C(O)R₅, nitro, -NR₆R₇, cyano, and a group R₈; R₁ is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkyl, halo C1-C6 alkoxy, halogen, NR₆R₇ or cyano; R₅ is a C1-C4 alkyl, -OR₆ or -NR₆R₇; R₆ is hydrogen or C1-C6 alkyl; R₇ is hydrogen or C1-C6 alkyl; R₈ is a 5-6 membered heterocycle, which may be saturated or may contain one to three double bonds, and which may be substituted by 1 or more R₁₁ groups; R₉ is a C1-C6 alkyl that may be substituted by one or more groups selected from: C3-C7 cycloalkyl, C1-C6 alkoxy, haloC1-C6 alkoxy, hydroxy, haloC1-C6 alkyl; R11 is C3-C7 cycloalkyl, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, hydroxy, halogen, nitro, cyano, or C(O)NR₆R₇; X is halogen; and R'' corresponds to R; R''₁ corresponds to R₁; R₂ is hydrogen, C3-C7 cycloalkyl, or a group R₉; R₃ is C3-C7 cycloalkyl, or a group R₉; or R₂ and R₃ together with N form a 5-14 membered heterocycle, which may be substituted by 1 to 3 R₁₀ groups; R''₄ is hydrogen; R''₅ corresponds to R₅; R''₆ corresponds to R₆; R''₇ corresponds to R₇; R''₈ corresponds to R₈; R''₉ corresponds to R₉; R₁₀ is a group R₈, C3-C7 cycloalkyl, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, hydroxy, halogen, nitro, cyano, C(O)NR₆R₇, phenyl which may be substituted by 1 to 4 R₁₁ groups; R''₁₁ corresponds to R₁₁.