反应详情

温度

130 °C

In a microwave tube was charged with methyl 4-[(5-bromo-2-pyridyl)amino]-4-oxo-butanoate (commercially available or prepared as described in example II using as starting material the commercially available: 5-bromo-2-aminopyridine; 200 mg, 0.696 mmol, 1 equiv.), 2-thienylboronic acid (3 equiv., 2.09 mmol, 3 equiv.), bis(tri-tert-butylphosphine)palladium(0) (22 mg, 0.043 mmol, 0.06 equiv.), potassium carbonate (179 mg, 1.28 mmol, 1.8 equiv.) and dissolved in glycol dimethyl ether (5 ml)/water (2 ml). The reaction mixture was heated at 130° C. for 20 minutes in the microwave. The reaction was stopped and the solution was partitioned between ethyl acetate and alkaline water. The aqueous layer was separated and extracted with ethyl acetate (2×). The combined organic layer was dried on magnesium sulfate, and then concentrated under vacuum. The solid obtained was purified by flash chromatography (RF-machine) eluting with a gradient of cyclohexane-ethyl acetate to give methyl 4-oxo-4-[[5-(2-thienyl)-2-pyridyl]amino]butanoate A71 (8%). %). LC-MS (Method F) RT 0.85, 291 (M+H+). The aqueous layer was acidified with hydrogen chloride until pH 1-2 and extracted with ethyl acetate (2×). The combined organic layer was dried on magnesium sulfate, and then concentrated under vacuum. The solid was washed with ethyl acetate, filtered and dried to give 4-oxo-4-[[5-(2-thienyl)-2-pyridyl]amino]butanoic acid A72 (31% yield). %). LC-MS (Method F) RT 0.74, 277 (M+H+).

1. customprepared
2. customthe solution was partitioned between ethyl acetate
3. customThe aqueous layer was separated
4. extractionextracted with ethyl acetate (2×)
5. customThe combined organic layer was dried on magnesium sulfate
6. concentrationconcentrated under vacuum
7. customThe solid obtained
8. customwas purified by flash chromatography (RF-machine)
9. washeluting with a gradient of cyclohexane-ethyl acetate