Hydrochloric Acid → HCID 58438624, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (200 mg, 0.39 mmol) (approx 3:1 mix of 5-Br & 5-Cl) and 3-carboxyphenylboronic acid (85.0 mg, 0.51 mmol) in 1,2-DME (4 mL) were added Pd(Ph3P)4 (22.8 mg, 0.02 mmol) and 2.0 M aqueous Na2CO3 (0.8 mL, 1.6 mmol). The reaction mixture was heated at 90° C. overnight then cooled to room temp and diluted with water. The pH was adjusted to 6 with 1.0 M HCl before extracting with EtOAc (2×). The combined organics were dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (0% to 4% MeOH/CH2Cl2 (0.5% NH4OH)) to afford 145 mg (67%) of 3-[7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-benzoic acid as a white foamy solid.

Provenance & Evidence