Toluene → HCID 66599389, compound

Participants

Reaction Conditions

Reaction Steps

A 125 ml pressure flask was loaded with tert-butyl 4-(4-(4-bromo-2-cyanophenylamino)benzoyl)piperazine-1-carboxylate (6.55 g, 13.49 mmol), 3-fluoro-4-methoxyphenylboronic acid (2.75 g, 16.19 mmol) and Pd(Ph3P)4 (0.43 g, 0.372 mmol). Toluene (45 mL), MeOH (22.50 mL) and a 2 molar solution of Na2CO3 (16.87 mL, 33.7 mmol) were added, the flask flushed with nitrogen, sealed and heated to 105° C. for 5 hours. The reaction mixture was poured into a separating funnel loaded with water and dichloromethane, the layers separated and the aqueous layer extracted one more time with dichloromethane. The combined organic layers were washed with brine and dried over MgSO4, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica. Gradient from 100% CH2Cl2 to 67% CH2Cl2+33 ethyl acetate. Product containing fractions were combined and concentrated in vacuum. 6.88 g tert-butyl 4-(4-(3-cyano-3′-fluoro-4′-methoxybiphenyl-4-ylamino)benzoyl)-piperazine-1-carboxylate were isolated as a pale yellow foam of ˜80% purity. The material was used in then next step without further purification. MS (ESI) m/z 529 (M−H).

Provenance & Evidence