反応 #1994291

反応方程式

6-Amino-2,5-dichloropyrimidine-4-carboxylic acid methyl ester

cesium fluoride

4-chloro-2-fluorophenylboronic acid

→

title compound

収率 40.8%

6-Amino-5-chloro-2-(4-chloro-2-fluorophenyl)pyrimidine-4-carboxylic acid methyl ester

収率 40.8%

溶媒

water

1,2-dimethoxyethane

ethyl acetate

反応条件

後処理

1. 1
   その他The cooled reaction mixture
2. 2
   洗浄washed with water
3. 3
   その他dried
4. 4
   濃縮concentrated
5. 5
   その他The product was purified by column chromatography (methylene chloride/ethyl acetate gradient)
6. 6
   その他then purified again by column chromatography (ethyl acetate/hexane gradient)

実験手順

6-Amino-2,5-dichloropyrimidine-4-carboxylic acid methyl ester (1.11 g, 5 mmol, see WO 2007/082076 A1 for preparation), 4-chloro-2-fluorophenylboronic acid (1.13 g, 6.5 mmol), bis(triphenylphosphine)-palladium(II) dichloride (350 mg, 0.5 mmol), and cesium fluoride (1.52 g, 10 mmol) were combined in 10 mL of 1,2-dimethoxyethane (DME) and 10 mL of water. The reaction mixture was heated in a CEM microwave at 100° C. for 15 minutes. The cooled reaction mixture was diluted with ethyl acetate, washed with water, dried and concentrated. The product was purified by column chromatography (methylene chloride/ethyl acetate gradient) then purified again by column chromatography (ethyl acetate/hexane gradient) to yield the title compound (574 mg, 40.8% yield): mp 194-196° C.; 1H NMR (CDCl3): δ 7.96 (m, 1H), 7.2 (m, 2H), 5.64 (br s, 2H), 4.01 (s, 3H).

出典