Reacción #48882

Ecuación de reacción

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

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

2-Amino-5-methylpyrazine

pyridine

→

desired compound

Rendimiento 12.4%

3-[4-(Azetidin-1-ylcarbonyl)-2-chlorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-pyrazin-2-ylbenzamide

Rendimiento 12.4%

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 (10 mL) was added
4. 4
   Extracciónthe mixture extracted with ethyl acetate (2×10 mL)
5. 5
   Lavadowashed with 1N citric acid, water (10 mL) and brine (10 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 (0.073 mL, 0.55 mmol) was added to a solution of 3-[4-(azetidin-1-ylcarbonyl)-2-chlorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid (260 mg, 0.5 mmol) in DCM (10 mL) and stirred at RT for 1 hour. 2-Amino-5-methylpyrazine (95 mg, 1 mmol) and pyridine (0.081 mL, 1.0 mmol) were added and the reaction stirred for a further 30 mins. The solvent was removed in vacuo. Water (10 mL) was added and the mixture extracted with ethyl acetate (2×10 mL). The extracts were combined and washed with 1N citric acid, water (10 mL) and brine (10 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 (37 mg).

Fuente