Isopropanol → 4-Chloro-6-(3,4-dimethoxyphenyl)-2-(methylthio)pyrimidine

Participants

Reaction Conditions

Reaction Steps

Argon is bubbled through a mixture of 4,6-dichloro-2-(methylthio)pyrimidine [4.98 g, 25.55 mmol, Intermediate (29)], 3,4-dimethoxyphenylboronic acid [3.874 g, 21.29 mmol, Intermediate (32)], and Cs2CO3 (17.34 g, 53.23 mmol) in ethylene glycol dimethyl ether (56 mL) and water (14 mL), for a period of 15 minutes. To this mixture is added tetrakis(triphenylphosphine)palladium (0) (1.22 g, 1.06 mmol) the reaction vessel is heated to 100° C. After stirring overnight the mixture is diluted with water (250 mL) and extracted three times with EtOAc (100 mL). The organic extracts are combined, washed with brine (100 mL), and dried over magnesium sulfate. The mixture is filtered and concentrated to provide a solid that is dissolved in boiling isopropyl alcohol (40 mL) and allowed to cool to ambient temperature. After standing for 24 hours the solid is collected by filtration, washed with cold isopropyl alcohol and dried under high vacuum to afford 4-chloro-6-(3,4-dimethoxy-phenyl)-2-methylsulfanyl-pyrimidine [5.28 g, 83.5%, Intermediate (48)].

Provenance & Evidence