反应详情

温度

105 °C

t-Amyl alcohol (41 mL) was placed in a flask and argon was bubbled through it for several minutes. 2-Amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (2.50 g, 8.0 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (1.90 g, 4 mmol), Pd2(dba)3 (0.73 g, 0.8 mmol), and potassium carbonate (1.22 g, 8.8 mmol) were placed in a reaction vessel that was purged with argon. Degassed t-amyl alcohol (10 mL) was used to transfer 1-[(6-bromopyridin-2-yl)methoxy]-2-methylpropan-2-ol (2.08 g, 8.0 mmol) to the reaction vessel and the remaining t-amyl alcohol was added. Seven argon/vacuum cycles were performed. The solution was heated at 105° C. overnight. The reaction was then cooled to ambient temperature, diluted with methanol, and silica gel was added. The resulting mixture was concentrated in vacuo and then purified by column chromatography (silica, 0-5% methanol/ethyl acetate). Purification via mass guided reverse phase HPLC (Agilent 1100 HPLC-MSD, Phenomenex Gemeni-C18, 10 μM, 250 mm×50 mm i.d. column, 20-95% acetonitrile/water+0.01% formic acid modifier, 75-100 mL/min flow rate) afforded the title compound.

1. customargon was bubbled through it for several minutes
2. customthat was purged with argon
3. temperatureThe reaction was then cooled to ambient temperature
4. additionwas added
5. concentrationThe resulting mixture was concentrated in vacuo
6. custompurified by column chromatography (silica, 0-5% methanol/ethyl acetate)
7. customPurification via mass