Sodium Carbonate → HCID 66604798, compound

Participants

Reaction Conditions

Reaction Steps

A 5 ml microwave vial was loaded with 5-bromo-2-(4-(morpholine-4-carbonyl)phenylamino)benzonitrile (125 mg, 0.259 mmol, Example 160A), 2-benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (79 mg, 0.362 mmol) and Pd(Ph3P)4 (15 mg, 0.013 mmol). Toluene (1 mL), MeOH (0.500 mL) and a 2 molar solution of Na2CO3 (0.324 mL, 0.647 mmol) were added, the flask flushed with nitrogen, sealed and heat to 110° C. for 4 hours. LCMS after 4 hours showed product and starting material (1:2.5 ratio) (product m/e−=396, consistent with [M−H]−). Additional 2-benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (400 mg, 1.834 mmol) and Pd(Ph3P)4 (30 mg, 0.026 mmol), Toluene (1 mL), MeOH (0.500 mL) and a 2 molar solution of Na2CO3 (0.324 mL, 0.647 mmol) were added. The flask was flushed with nitrogen, sealed and heated to 110° C. for additional 8 hours. The reaction mixture was poured into a separating funnel loaded with water and dichloromethane. The layers were 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, using a gradient from 100% CH2Cl2 to 50% CH2Cl2+50 EtOAc. Product containing fraction were combined and evaporated to dryness to give 42.3 mg 5-benzyl-2-(4-(morpholine-4-carbonyl)phenylamino)benzonitrile. (estimated purity 76%). The material was used without further purification. MS (ESI) m/e−=396, m/e+=398 consistent with [M−H]− and [M+H]+.

Provenance & Evidence