反应 #593644

反应方程式

water

6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester

trans-propenyl boronic acid

cesium fluoride

→

title compound

6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-((E)-propenyl)pyrimidine-4-carboxylic acid methyl ester

溶剂

1,2-dimethoxyethane

反应条件

后处理

1. 1
   其他The cooled reaction mixture
2. 2
   其他was partitioned between ethyl acetate and water
3. 3
   其他and the organic phase was dried
4. 4
   浓缩concentrated
5. 5
   其他The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)
6. 6
   其他then purified again by reverse phase HPLC

实验过程

6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester (400 mg, 1.02 mmol), trans-propenyl boronic acid (2132 mg, 1.54 mmol), bis(triphenylphosphine)palladium(II) dichloride (72 mg, 0.1 mmol), and cesium fluoride (311 mg, 2.05 mmol) were combined in 1,2-dimethoxyethane (2 mL) and water (2 mL) and heated at 100° C. for 15 min in a CEM microwave reactor. The cooled reaction mixture was partitioned between ethyl acetate and water; and the organic phase was dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) then purified again by reverse phase HPLC to yield the title compound: mp 133-135° C.: 1H NMR (CDCl3) δ 7.63 (m, 1H), 7.22 (m, 1H), 6.43 (m, 1H), 6.12 (m, 1H), 5.35 (br s, 2H), 3.99 (d, 3H), 3.94 (s, 3H), 1.94 (dd, 3H).

来源