4-tributylstannanyl-1-(2,3,5-trifluoro-phenyl)-1H-imidazole → 2-[1-(2,3,5-trifluoro-phenyl)-1H-imidazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Participants

Reaction Conditions

Reaction Steps

To the crude 4-tributylstannanyl-1-(2,3,5-trifluoro-phenyl)-1H-imidazole from Step 3 was added crude 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (0.087 g, from Step 1) in 3 mL of DMF, Pd(PPh3)4 (0.032 g, 0.027 mmol) and CuI (0.021 g, 0.110 mmol). The dark yellow mixture was stirred at 80° C. for 16 h, then allowed to cool. The mixture was partitioned between 20 mL of ethyl acetate and 20 mL of a sat. aq. NH4Cl solution. The organic layer was washed with 20 mL of water+20 mL of a sat. aq. NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. Column chromatography (0-10% MeOH/EtOAc) of the residue afforded 0.005 g (5%) of 2-[1-(2,3,5-trifluoro-phenyl)-1H-imidazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a yellow solid, ca. 85% pure. MS: (M+Na)+=543.

Provenance & Evidence