2-CHLORO-7,8-DIHYDRO-1,7-NAPHTHYRIDIN-8-ONE can be prepared by first oxidizing 7H-[1,7]naphthodi-8-one as a raw material to prepare 1-oxy-7H-[1,7]naphthodi-8-one, and then chlorinating it.
Step 1: 1-Oxy-7H-[1,7]naphthidium-8-one
3-chloroperbenzoic acid (4.3 g, 70%, 17 mmol) was added to 100 ml of a chloroform solution of 7H-[1,7]naphthidium-8-one (2.3 g, 16 mmol) (the preparation of 7H-[1,7]naphthidium-8-one is described in Chem. Pharm. Bull. 1985, 33(2), 626). After stirring at room temperature for 70 hours, the mixture was dissolved by adding methanol. Aminopropyl-modified silica gel was added and the mixture was concentrated to dryness. The residue was transferred to an aminopropyl-modified silica column. Elution with dichloromethane/methanol yielded a yellow solid, 1-oxy-7H-[1,7]naphthyl-8-one (2.4 g, 94%), MSm/e(%) = 163 (M+H+, 100).
Step 2: 2-Chloro-1,7-Naphthyl-8(7H)-one>
Oxaloyl chloride (0.77 ml, 9.0 mmol) was added dropwise to 45 ml of a dry N,N-dimethylformamide suspension of 1-oxy-7H-[1,7]naphthyl-8-one (1.1 g, 6.9 mmol) at 0 °C. After addition, the mixture was heated to room temperature and stirred for 30 min. Methanol was added to dissolve excess oxalyl chloride, and the mixture was then concentrated under vacuum. The residue was redissolved in methanol and treated with aminoamino-modified silica gel. The solvent was evaporated, and the residue was then transferred to an aminopropyl-modified silica column. Eluting with dichloromethane/methanol yielded a white solid, 2-CHLORO-7,8-DIHYDRO-1,7-NAPHTHYRIDIN-8-ONE (0.72 g, 57%), MS m/e (%) = 181 (M+H+, 100).
