Reacción #48796

Ecuación de reacción

2-amino-5 methylpyrazine

pyridine

3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoic acid

oxalyl chloride

→

desired compound

Rendimiento 98.2%

3-{[(1S)-1-Methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)-5-[(phenylmethyl)oxy]benzamide

Rendimiento 98.2%

Disolventes

DCM

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe DCM and excess oxalyl chloride evaporated in vacuo
2. 2
   workup.DISSOLUTIONThe residual acid chloride was dissolved in DCM
3. 3
   workup.STIRRINGStirred at ambient temperature for 24 hours
4. 4
   OtroThe DCM was evaporated in vacuo
5. 5
   Otrothe residue partitioned between ethyl acetate (100 mL) and 1N hydrochloric acid (50 mL)
6. 6
   LavadoThe ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL)
7. 7
   Secadodried (MgSO4)
8. 8
   Otroevaporated in vacuo
9. 9
   OtroThe residue was chromatographed on silica
10. 10
    Lavadoeluting with a gradient of 30-100% ethyl acetate in isohexane

Procedimiento

DMF (2 drops) was added to a solution of 3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoic acid (6.0 g, 19.0 mmol) and oxalyl chloride (1.99 mL, 22.8 mmol) in DCM (40 mL) The mixture was stirred at ambient temperature for 2 hours and the DCM and excess oxalyl chloride evaporated in vacuo. The residual acid chloride was dissolved in DCM and added dropwise to 2-amino-5 methylpyrazine [Tett lett. 2002, 9287-90] (2.28 g, 19.8 mmol) and pyridine (2.56 mL, 38 mmol) in DCM (40 mL), at 0° C. Stirred at ambient temperature for 24 hours. The DCM was evaporated in vacuo, and the residue partitioned between ethyl acetate (100 mL) and 1N hydrochloric acid (50 mL). The ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL), dried (MgSO4), and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 30-100% ethyl acetate in isohexane, to give the desired compound (7.6 g)

Fuente