Pd-catalyzed coupling of pyrazole amides

摘要

A novel process for the preparation of imidazo[1,2-a]pyridine compounds of the formula;whereinR1 is C1-4-alkoxy or NR4R5 wherein
R4 and R5 are independently hydrogen or C1-4-alkyl orR4 and R5, together with the nitrogen atom to which they are attached, form a saturated 4- to 6-membered heterocyclic ring which may contain one further heteroatom selected from nitrogen or oxygen;R2 is C1-4-alkyl, C1-4-alkoxycarbonyl, halogen, phenyl which is optionally substituted with C1-4-alkyl, C1-4-alkoxy or halogen or is NR4R5 wherein
R4 and R5 are independently hydrogen or C1-4-alkyl orR4 and R5, together with the nitrogen atom to which they are attached, form a saturated 4- to 6-membered heterocyclic ring which may contain one further heteroatom selected from nitrogen or oxygen;R3 is C1-4-alkyl andX is nitrogen or CHis described.;The imidazo[1,2-a]pyridine compounds of the formula I are either precursors for active principles or active principles itself, acting as phosphodiesterase (PDE) inhibitors, particularly PDE10 inhibitors which have the potential to treat psychotic disorders like schizophrenia (Int. Patent Publication WO 2012/076430).

主权项

1. A process for the preparation of imidazo[1,2-a]pyridine compounds of the formula (I) wherein R1 is C1-4-alkoxy or NR4R5 wherein
R4 and R5 are independently hydrogen or C1-4-alkyl, or,R4 and R5, together with the nitrogen atom to which they are attached, form a saturated 4- to 6-membered heterocyclic ring which may contain one additional heteroatom selected from nitrogen or oxygen; R2 is C1-4-alkyl, C1-4-alkoxycarbonyl, halogen, phenyl which is optionally substituted with C1-4-alkyl, C1-4-alkoxy or halogen or is NR4R5 wherein R4 and R5 are independently hydrogen or C1-4-alkyl or
R4 and R5, together with the nitrogen atom to which they are attached, form a saturated 4- to 6-membered heterocyclic ring which may contain one further heteroatom selected from nitrogen or oxygen; R3 is C1-4-alkyl and X is nitrogen or CH; comprising the reaction of a pyrazole carboxamide derivative of formula (II) wherein R1 and R3 are as above; with a halogen imidazo[1,2-a]pyridine derivative of the formula wherein R2 and X are as above and Y is halogen, C1-4-alkylsulfonyloxy, mono- or polyhalogen-C1-4-alkylsulfonyloxy, mono- or poly-C1-4-alkylphenylsulfonyloxy or phenylsulfonyloxy; in the presence of a palladium catalyst, a base and an organic solvent.