反应详情

温度

100 °C

A suspension of 8-chloro-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (500 mg, 2.38 mmol), 4-bromo-2-fluoroaniline (543 mg, 2.86 mmol), Pd2dba3 (110 mg, 0.12 mmol), 2-dicyclohexylFphosphino-2′,6′-diisopropoxybiphenyl (224 mg, 0.48 mmol) and K3PO4 (710 mg, 3.33 mmol) in toluene (10 mL) was degassed and then heated at 100° C. for 18 hours. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate and filtered. The filtrate was washed with water and brine, then loaded onto a 10 g Isolute® SCX-2 cartridge which was eluted with methanol and then a 2M solution of ammonia in methanol. The appropriate fractions were combined and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 20%, ethyl actetate in DCM) to afford the title compound as a yellow oil (240 mg, 28%). LCMS (method B): RT=3.40 min, [M+H]+=364/366.

1. customwas degassed
2. temperatureThe reaction mixture was then cooled to room temperature
3. additiondiluted with ethyl acetate
4. filtrationfiltered
5. washThe filtrate was washed with water and brine
6. washwas eluted with methanol
7. concentrationconcentrated in vacuo