Reacción #588

Ecuación de reacción

CCOC(=O)c1ccc(Cl)nc1

CCOC(=O)c1cnc(N)o1

→

CCOC(=O)c1ccc(Nc2ncc

Rendimiento 67.2%

Disolventes

C1COCCO1

Condiciones de reacción

Procedimiento

Objective: Test of scope in the coupling of ester substituted aminooxazole To an oven-dried microwave vial was added ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.075 mmol) and the vial was capped and purged with nitrogen. ethyl 6-chloronicotinate (185 mg, 1.00 mmol) and dioxane (4 mL) (degassed) were added and the reaction mixture was heated to 160 °C for 1 h under microwave irradiation. LCMS of the crude reaction mixture indicated that the desired product had formed with minimal formation of side-products. DCM (20 mL) was added to the crude reaction mixture together with silica (2 g). The solvent was removed under reduced pressure and the resulting residue was placed in a dry-load tube prior to chromatography. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% Methanolic ammonia in DCM. Pure fractions were evaporated to dryness to afford the desired product (270 mg, 88% isolated yield in 86% purity). This solid was triturated with hot MeCN and allowed to cool to room temperature to give a solid which was collected by filtration and dried under vacuum to give ethyl 2-(5-(ethoxycarbonyl)pyridin-2-ylamino)oxazole-5-carboxylate (205 mg, 67.2 %) as a cream solid. Conclusion: The desired product was isolated in moderate yield and high purity.

Fuente