Réaction #2075725

Équation de réaction

6-Amino-2-chloro-5-methoxypyrimidine-4-carboxylic acid methyl ester

cesium fluoride

4-chloro-2-fluoro-3-methoxyphenylboronic acid

→

title compound

Rendement 52.7%

6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-methoxypyrimidine-4-carboxylic acid methyl ester

Rendement 52.7%

Solvants

water

1,2-dimethoxyethane

ethyl acetate

Conditions de réaction

Traitement

1. 1
   AutreThe cooled reaction mixture
2. 2
   Lavagewashed with water
3. 3
   Lavagewashed with brine
4. 4
   Autredried
5. 5
   Concentrationconcentrated
6. 6
   AutreThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

Mode opératoire

6-Amino-2-chloro-5-methoxypyrimidine-4-carboxylic acid methyl ester (0.2 g, 0.9 mmol), 4-chloro-2-fluoro-3-methoxyphenylboronic acid (0.29 g, 1.4 mmol), bis(triphenylphosphine)palladium(II) dichloride (65 mg, 0.1 mmol), and cesium fluoride (0.28 g, 1.9 mmol) were combined in 1 mL of 1,2-dimethoxyethane and 1 mL of water. The reaction mixture was heated in a CEM microwave at 100° C. for 15 min (other temperature/time pairs used in the subsequent examples were 110° C. for 15 min and 150° C. for 5 min). The cooled reaction mixture was diluted with ethyl acetate, washed with water, washed with brine, dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to yield the title compound (162 mg, 51.1% yield): mp 155-158° C.; 1H NMR (CDCl3): δ 7.58 (dd, 1H), 7.20 (dd, 1H), 5.56 (br s, 2H) 4.00 (s, 3H), 3.99 (d, 3H), 3.94 (s, 3H).

Source