反应详情

温度

100 °C

In a 250 mL round-bottomed flask, 6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)nicotinic acid (195 mg, 695 μmol), 4-methylpiperidin-4-ol (80.0 mg, 695 μmol), HOBT (138 mg, 903 μmol) and Hunig's base (269 mg, 364 μl, 2.08 mmol) were combined with DMF (13 ml) to give a light yellow suspension. EDC (173 mg, 903 μmol) was added and the reaction mixture was heated to 100° C. and stirred for 24 h. Additional 4-methylpiperidin-4-ol (80.0 mg, 695 μmol), HOBT (106 mg, 695 μmol) and EDC (133 mg, 695 μmol) were added with 2 ml DMF. The reaction mixture was heated to 100° C. and stirred for 24 h. The reaction was cooled to 25° C. and quenched with water. The aqueous layer was back-extracted with EtOAc (3×75 mL). The organic layers were combined, washed with sat NaCl (1×50 mL), dried over Na2SO4 and concentrated in vacuo. The residue was taken up in DCM/MeOH 9:1 and filtered. The filtrate was conc. in vacuo to give a light yellow solid. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 10% MeOH in DCM) to afford 0.033 g (13%) of the title compound as a yellow solid. (M+H)+=378/380 m/e.

1. customto give a light yellow suspension
2. temperatureThe reaction mixture was heated to 100° C.
3. stirringstirred for 24 h
4. temperatureThe reaction was cooled to 25° C.
5. customquenched with water
6. extractionThe aqueous layer was back-extracted with EtOAc (3×75 mL)
7. washwashed with sat NaCl (1×50 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo
10. filtrationfiltered
11. customto give a light yellow solid
12. customThe crude material was purified by flash chromatography (silica gel, 12 g, 0% to 10% MeOH in DCM)