Reacción #47633

Ecuación de reacción

2-amino-3-bicyclo[2.2.1]hept-2-yl-propionic acid methyl ester

N,N-diisopropylethylamine

4-bromo-3-(2,6-difluoro-phenoxy)-but-2-enoic acid ethyl ester

(S)-3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide

→

3-bicyclo[2.2.1]hept-2-yl-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid methyl ester

Rendimiento 21.4%

Disolventes

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroIn a round bottom flask was placed
2. 2
   OtroThis mixture was then split into two 5 mL portions
3. 3
   Otroplaced in two sealed microwave reaction tubes
4. 4
   OtroThe contents of the two reaction tubes
5. 5
   Concentraciónconcentrated in vacuo
6. 6
   workup.ADDITIONdiluted with dichloromethane (20 mL)
7. 7
   Lavadowashed with a 1N aqueous hydrochloric acid solution (10 mL)
8. 8
   Secadoa saturated sodium bicarbonate solution (10 mL), dried over magnesium sulfate
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated in vacuo
11. 11
    OtroPurification by AnaLogix IntelliFlash flash chromatography (12 g column, 15% ethyl acetate/hexanes to 30% ethyl acetate/hexanes)

Procedimiento

In a round bottom flask was placed 2-amino-3-bicyclo[2.2.1]hept-2-yl-propionic acid methyl ester (206 mg, 1.04 mmol), N,N-diisopropylethylamine (390 μL, 2.24 mmol) and 4-bromo-3-(2,6-difluoro-phenoxy)-but-2-enoic acid ethyl ester (prepared as in Example 36, 390 mg, 2.24 mmol) in acetonitrile (10 mL). This mixture was then split into two 5 mL portions and placed in two sealed microwave reaction tubes and heated in a microwave reactor at 140° C. for 1 h. The contents of the two reaction tubes were combined, concentrated in vacuo and diluted with dichloromethane (20 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), a saturated sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (12 g column, 15% ethyl acetate/hexanes to 30% ethyl acetate/hexanes) afforded 3-bicyclo[2.2.1]hept-2-yl-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid methyl ester (87 mg, 15%) as a yellow oil.

Fuente