反应详情

温度

110 °C

3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate A4) (3 g, 10.03 mmol), 2,4-dichlorophenylboronic acid (2.297 g, 12.04 mmol), potassium phosphate (4.26 g, 20.06 mmol) and Fibrecat® 1034A (Johnson Matthey, polymer supported palladium complex) (500 mg, 10.03 mmol) were suspended in toluene (50 ml) and water (15 ml). The reaction mixture was heated to 110° C. under vigorous stirring for 3 hours. The mixture was allowed to cool to RT and EtOAc (100 ml) was added. The organic layer was separated and washed with brine (15 ml). MP-TMT (macroporous polystyrene-bound trimercaptotriazine, 3 g, Polymern labs) was added and stirred for 1 hour at RT. MgSO4 was added and the suspension filtered off. The filtrate was concentrated in vacuo and purification of the residue by reverse phase chromatography (130 g C18 column) eluting with water/MeOH afforded the title compound as a white solid; LS-MS Rt=1.55 mins [M+H]+ 365 (Method 2 minLC_v002).

1. temperatureto cool to RT
2. customThe organic layer was separated
3. washwashed with brine (15 ml)
4. additionMP-TMT (macroporous polystyrene-bound trimercaptotriazine, 3 g, Polymern labs) was added
5. stirringstirred for 1 hour at RT
6. additionMgSO4 was added
7. filtrationthe suspension filtered off
8. concentrationThe filtrate was concentrated in vacuo and purification of the residue by reverse phase chromatography (130 g C18 column)
9. washeluting with water/MeOH