[O:1]=[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6][NH:5][C:4]2[N:13]=[CH:14][CH:15]=[CH:16][C:3]1=2.[I:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1.[H-].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O.O>[I:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][N:5]2[C:4]3[N:13]=[CH:14][CH:15]=[CH:16][C:3]=3[C:2](=[O:1])[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6]2)=[CH:20][CH:19]=1Ethyl 4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate (1.00 g, 4.56 mmol) and 2-chloro-5-(chloromethyl)pyridine [(Example 5, Step 1), 500 mg, 2.28 mmol] and 4-iodobenzylbromide (745 mg, 2.51 mmol, 1.1 equiv) were dissolved in degassed N,N-dimethylformamide (5 mL) and cooled to 0° C. The mixture was treated with sodium hydride (109 mg, 2.74 mmol, 1.2 equiv) portionwise over 5 minutes. After stirring for 2 hours at 0° C., the mixture was warmed to ambient temperature and stirred for an additional 2 hours. The mixture was treated with sodium bicarbonate (10 mL, aqueous saturated), poured into water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried with sodium sulfate, filtered, concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound.
불러오는 중…
