Hydrochloric Acid → 5-(4-Chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)-2-methoxybenzoic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 4,6-dichloro-2-(4-phenoxyphenyl)nicotinonitrile (41.2 mg, 0.121 mmol, from Step 3 of Example 152), 5-borono-2-methoxybenzoic acid (18.9 mg, 0.096 mmol), palladium(II) acetate (4 mg, 0.018 mmol), potassium phosphate (125.8 mg, 0.593 mmol) and 1,1′-bis(di-t-butylphosphino)ferrocene (8.3 mg, 0.017 mmol) in N,N-dimethylformamide (0.5 mL) was pumped and backfilled with nitrogen twice. The reaction vial was then sealed and heated to 85° C. for 3 h. The crude material was poured into a mixture of ethyl acetate (20 mL) and diluted HCl (1 mmol, 5 mL). The aqueous pH was tested as pH 5. The ethyl acetate phase was concentrated and purified by reverse phase HPLC (Sunfire S10 30×250 mm column), eluting with 80-100% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA), to give impure 5-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)-2-methoxybenzoic acid (43 mg). This material was taken to next reaction without further purification. MS (ES+) m/z: 457 (M+H).

Provenance & Evidence