Реакция #187

ord-ad4a7da8a91e4c23abc6ab58d6712f3f

Уравнение реакции

Clc1cc(I)c(Cl)cn1
Clc1cc(I)c(Cl)cn1
CNC(=O)c1ccc(F)cc1N
CNC(=O)c1ccc(F)cc1N
CNC(=O)c1ccc(F)cc1Nc1cc(Cl)ncc1Cl
CNC(=O)c1ccc(F)cc1Nc
Выход 11.0%

Растворители

Условия реакции

Температура
80°CELSIUS

Методика

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-4-fluoro-N-methylbenzamide (585 mg, 3.48 mmol) and 2,5-dichloro-4-iodopyridine (1000 mg, 3.65 mmol) in dioxane (40 mL) under nitrogen. The resulting suspension was stirred at 80 °C for 18hrs then cooled. Product and bis product suggested. Disappointing! The reaction mixture was evaporated to dryness and redissolved in EtOAc (150 mL), and washed sequentially with saturated NaHCO3 (2 x 100 mL), water (100 mL), and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered then evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford desired product as a yellow solid.

Источник

750 AstraZeneca ELN dataset