Reacción #48799

Ecuación de reacción

1-Chloro-N,N,2-trimethyl-1-propenylamine

3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid

2-Amino-5-methylpyrazine

pyridine

→

desired compound

Rendimiento 101.6%

3-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-(5-methylpyrazin-2-yl)benzamide

Rendimiento 101.6%

Disolventes

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe reaction stirred for a further 30 mins
2. 2
   OtroThe solvent was removed in vacuo
3. 3
   workup.ADDITIONWater (100 mL) was added
4. 4
   Extracciónthe mixture extracted with ethyl acetate (3×50 mL)
5. 5
   Lavadowashed with water (1100 mL), brine (100 mL)
6. 6
   Secadodried (MgSO4)
7. 7
   Filtraciónfiltered
8. 8
   Otroevaporated in vacuo
9. 9
   Otroto give the crude product which
10. 10
    Otrowas chromatographed on silica
11. 11
    Lavadoeluting with a gradient of 50-100% ethyl acetate in isohexane

Procedimiento

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.86 g, 6.56 mmol) was added to a solution of 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid (3 g, 5.96 mmol) in DCM (100 mL) and stirred at RT for 11 hour. 2-Amino-5-methylpyrazine (1.3 g, 11.9 mmol) and pyridine (0.94 mL, 11.9 mmol) were added and the reaction stirred for a further 30 mins. The solvent was removed in vacuo. Water (100 mL) was added and the mixture extracted with ethyl acetate (3×50 mL). The extracts were combined and washed with water (1100 mL), brine (100 mL), dried (MgSO4), filtered, and evaporated in vacuo to give the crude product which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (3.6 g).

Fuente