Reacción #1994293

Ecuación de reacción

6-amino-5-chloro-2-(4-chloro-2-fluorophenyl)-pyrimidine-4-carboxylic acid

HCl

acetyl chloride

ethyl acetate hexane

→

title compound

Rendimiento 63.5%

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

Rendimiento 63.5%

Disolventes

ethanol

ethanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooled in an ice bath
2. 2
   ConcentraciónThe reaction mixture was concentrated
3. 3
   Otrothe residue partitioned between ethyl acetate and water
4. 4
   OtroThe organic phase was dried
5. 5
   Concentraciónconcentrated
6. 6
   Otrothe product was purified by column chromatography (dichloromethane/ethyl acetate gradient)

Procedimiento

A 1N solution of HCl in ethanol was generated by adding 0.565 mL of acetyl chloride dropwise to 12 mL of ethanol cooled in an ice bath. This solution was added to 200 mg of 6-amino-5-chloro-2-(4-chloro-2-fluorophenyl)-pyrimidine-4-carboxylic acid and the resulting solution was heated at 62° C. overnight. The reaction mixture was concentrated and the residue partitioned between ethyl acetate and water. The organic phase was dried and concentrated, and the product was purified by column chromatography (dichloromethane/ethyl acetate gradient). A second chromatography utilizing an amine-functionalized silica gel column (Biotage KP-NH) and an ethyl acetate/hexane gradient solvent system yielded the title compound (139 mg, 63.5% yield): mp 131-132° C.: 1H NMR (CDCl3): δ 7.97 (m, 1H), 7.2 (m, 2H), 5.63 (br s, 2H), 4.48 (q, 2H), 1.44 (t, 3H).

Fuente