Piperidine → HCID 56837973, compound

Participants

Reaction Conditions

Reaction Steps

8-Bromo-1,6-naphthyridine-2-carboxamide (22.4 g, 99 mmol) produced in Example 12 (12a) was dissolved in piperidine (152 g, 1.78 mol), to which potassium carbonate (36.9 g, 267 mmol) and tetrabutylammonium iodide (TBAI) (11.8 g, 99 mmol) were then added, followed by stirring at 110° C. for four hours. Piperidine was distilled off under reduced pressure. Toluene and water were added to the residue thus obtained, and the resulting mixture was partitioned (the pH of the aqueous layer was adjusted to be weakly basic). The aqueous layer was extracted with dichloromethane again, and then combined with the toluene layer. The resulting mixture was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue thus obtained was sequentially purified by normal phase silica gel column chromatography ((after letting hexane:ethyl acetate, 50:50, flow through, applying ethyl acetate:methanol, 100:0-90:10, V/V), basic silica gel column chromatography (hexane:ethyl acetate, 100:0-0:100, V/V), and reverse phase silica gel column chromatography (water:acetonitrile, 90:10-60:40, V/V) to give the desired title compound (15.7 g, yield 69%).

Provenance & Evidence