2-Chloro-1,5-naphthyridine

(2) 2-chloro-l, 5-naphthyridine.; To a 50 mL round-bottomed flask was added 1, 5-naphthyridine N-oxide(l 98 mg, 1355 μmol), phosphorus oxychloride (2 mL, 21457 μmol). The reaction mixture was stirred at 100 A 250 mL round bottomed flask charged with 1, 5-naphthyridin-2(1H)-one (2.98 g, 20.37 mmol) and phosphorus oxychloride (40 ml, 437 mmol) was heated at 100° C. for 3 h. To the compound 0001-1 (2.76 g), phosphorous oxychloride (8.3 mL) was added, and the mixture was stirred at 100°C for 5 hours. The reaction solution which had been cooled to room temperature was added dropwise to a mixture of ethyl acetate (30 mL), water (30 mL), and sodium carbonate (9.57 g) in an ice-cooling bath over one hour. Further, water (10 mL) was added thereto, and sodium carbonate was added thereto until the pH reached 8.3. After stirring at room temperature for 10 minutes, the resulting mixture was subjected to liquid separation by the addition of ethyl acetate (270 mL) and water (200 mL). Further, the aqueous layer was extracted with ethyl acetate (200 mL) twice. The collected organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure to obtain a compound 0001-2 (2.86 g) was obtained as a pale yellow solid. 0001-2 A 250 mL round bottomed flask charged with 1, 5-naphthyridin-2(1H)-one (2.98 g, 20.37 mmol) and phosphorus oxychloride (40 ml, 437 mmol) was heated at 100 C. for 3 h. The reaction was cooled to room temperature and excess POCl3 was removed in vacuo. The residue was poured onto ice and neutralized with NaHCO3. The mixture was extracted with DCM (4*) and the combined organic layers were evaporated onto silica gel and purified by flash chromatography (ISCO (80 gram)) eluting with EtOAc:DCM (0:1'1:4) to give 1.08 g (32%, 2 steps) of a light-yellow amorphous solid. ESI-MS 164.9, 166.9 [M+1].To the compound 0001-1 (2.76 g), phosphorous oxychloride (8.3 mL) was added, and the mixture was stirred at 100C for 5 hours. The reaction solution which had been cooled to room temperature was added dropwise to a mixture of ethyl acetate (30 mL), water (30 mL), and sodium carbonate (9.57 g) in an ice-cooling bath over one hour. Further, water (10 mL) was added thereto, and sodium carbonate was added thereto until the pH reached 8.3. After stirring at room temperature for 10 minutes, the resulting mixture was subjected to liquid separation by the addition of ethyl acetate (270 mL) and water (200 mL). Further, the aqueous layer was extracted with ethyl acetate (200 mL) twice. The collected organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure to obtain a compound 0001-2 (2.86 g) was obtained as a pale yellow solid. 1H-NMR (DMSO-d6) delta: 9.05 (1H, dd), 8.50 (1H, dd, J=8.9), 8.41 (1H, ddd), 7.87, (1H, d), 7.86 (1H, m).

Molecular Weight:164.59
XLogP3:2.2
Hydrogen Bond Acceptor Count:2
Exact Mass:164.0141259
Monoisotopic Mass:164.0141259
Topological Polar Surface Area:25.8
Heavy Atom Count:11
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes