Reaction #168

ord-2bb50d74d5eb4051be498e22a50f1370

Reaction equation

Clc1cc(I)c(Cl)cn1
Clc1cc(I)c(Cl)cn1
CNC(=O)c1cc(F)ccc1N
CNC(=O)c1cc(F)ccc1N
CNC(=O)c1cc(F)ccc1Nc1cc(Cl)ncc1Cl
CNC(=O)c1cc(F)ccc1Nc
Yield 13.3%

Solvents

Conditions

Temperature
80°CELSIUS

Procedure

palladium acetate (31.2 mg, 0.14 mmol) was added to 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (121 mg, 0.21 mmol), Cesium carbonate (2266 mg, 6.95 mmol), 2-amino-5-fluoro-N-methylbenzamide (585 mg, 3.48 mmol) and 2,5-dichloro-4-iodopyridine (1000 mg, 3.65 mmol) in dioxane (20 mL) under nitrogen. The resulting suspension was stirred at 80 °C for 18hrs then cooled. Product appeared to be out of solution. Product and bis product suggested. Disappointing! The reaction mixture was evaporated to dryness and redissolved in EtOAc (100 mL), and washed sequentially with saturated Na2CO3 (50 mL), water (50 mL), and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford desired product as an beige solid.

Source

750 AstraZeneca ELN dataset