Reacción #331488

Ecuación de reacción

cesium fluoride

sodium 3,3′,3″-phosphinetriyltribenzenesulfonate

2-(4-Chloro-2,3-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

methyl 6-amino-2-chloropyrimidine-4-carboxylate

→

title compound

Rendimiento 68.3%

methyl 6-amino-2-(4-chloro-2,3-difluorophenyl)-pyrimidine-4-carboxylate

Rendimiento 68.3%

Disolventes

water

water

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe cooled reaction mixture
2. 2
   Extracciónextracted with dichloromethane (5×100 mL)
3. 3
   SecadoThe combined organic layers were dried (magnesium sulfate)
4. 4
   Filtracióngravity-filtered
5. 5
   Concentraciónconcentrated under vacuum
6. 6
   OtroThe product was purified by flash chromatography (SiO2, 40% ethyl acetate in hexane)

Procedimiento

2-(4-Chloro-2,3-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.4 g, 5.1 mmol, 1.2 equiv) and methyl 6-amino-2-chloropyrimidine-4-carboxylate (800 mg, 4.3 mmol, 1.0 equiv) were sequentially added to a 20 mL Biotage microwave vessel, followed by cesium fluoride (1.3 g, 8.5 mmol, 2.0 equiv), palladium(II) acetate (38 mg, 0.17 mmol, 0.04 equiv), and sodium 3,3′,3″-phosphinetriyltribenzenesulfonate (190 mg, 0.34 mmol, 0.08 equiv). A 3:1 mixture of water:acetonitrile (8.5 mL) was added and the resulting brown mixture was placed in a Biotage microwave and heated at 150° C. for 5 m. The cooled reaction mixture was diluted with water (300 mL) and extracted with dichloromethane (5×100 mL). The combined organic layers were dried (magnesium sulfate), gravity-filtered, and concentrated under vacuum. The product was purified by flash chromatography (SiO2, 40% ethyl acetate in hexane) to afford the title compound as an off-white powder (880 mg, 68% yield): mp 192-195° C.; 1H NMR (300 MHz, CDCl3) δ 7.77 (m, 1H), 7.21-7.28 (m, 2H), 7.15 (s, 1H), 5.23 (br s, 2H), 4.00 (s, 3H); IR (neat film) 3493 (w), 3393 (m), 3342 (m), 3211 (s), 1730 (m), 1649 (m); ESIMS m/z 300 ([M+H]+).

Fuente