2-Amino-7-hydroxy-1,8-naphthyridine

Yellow-Brown Solid

8.9 5-(4-Butyrylpiperazin-1-yl)carbonyloxy-6-(7-chloro-1, 8-naphthyridin-2-yl)-7-oxo-2, 3, 6, 7-tetrahydro-5H-1, 4-dithiino[2, 3-c]pyrrole (1.95 g.), which melts at 248 C., is thus obtained. 6-(7-Chloro-1, 8-naphthyridin-2-yl)-7-oxo-5-(piperazin-1-yl)carbonyloxy-2, 3, 6, 7-tetrahydro-5H-1, 4-dithiino[2, 3-c]pyrrole employed as starting material can be prepared in the following manner: 5-(4-t.-Butoxycarbonylpiperazin-1-yl)carbonyl-oxy-6-(7-chloro-1, 8-naphthyridin-2-yl)-7-oxo-2, 3, 6, 7-tetrahydro-5-H-1, 4-dithiino[2, 3-c]pyrrole (3.40 g.) is added, over the course of 20 minutes, to trifluoroacetic acid (14 cc.) cooled to between -5 and -10 C. The solution obtained at the end of the addition is kept for a further half an hour at the same temperature and is then diluted with ice-water (140 cc.). The resulting precipitate is filtered off, washed twice with distilled water (total 50 cc.) and treated, until complete dissolution has taken place, with 2N aqueous sodium hydroxide solution (100 cc.) and methylene chloride (150 cc). The organic solution is washed three times with distilled water (total 150 cc.), dried over anhydrous sodium sulphate, treated with decolourising charcoal (0.2 g.) and evaporated. The crystals obtained are washed with boiling acetonitrile (40 cc.). 6-(7-Chloro, 1, 8-naphthyridin-2-yl)-7-oxo-5-(piperazin-1-yl)-carbonyloxy-2, 3, 6, 7-tetrahydro-5-H-1, 4-dithiino[2, 3-c]-pyrrole (2.20 g.), which melts at 300 C. with decomposition, is obtained. 5-(4-t.-Butoxycarbonylpiperazin-1-yl)-carbonyloxy-6-(7-chloro-1, 8-naphthyridin-2-yl)-7-oxo-2, 3, 6, 7-tetrahydro-5H-1, 4-dithiino[2, 3-c]pyrrole can be prepared by treating 6-(7-chloro-1, 8-naphthyridin-2-yl)-5-hydroxy-7-oxo-2, 3, 6, 7-tetrahydro-5H-1, 4-dithiino-[2, 3-c]pyrrole (40.5 g.) with sodium hydride (3.15 g.) in anhydrous dimethylformamide (400 cc.) at 2 C., and by adding a solution of 4-chlorocarbonyl-1-t.-butoxycarbonylpiperazine (45.0 g.) in anhydrous dimethylformamide (200 cc.). The reaction mixture is kept at 2 C. for 2 hours and is then diluted with ice-water (3, 000 cc.). The precipitate obtained is filtered off, washed three times with distilled water (total 600 cc.) and dried by means of warm air (approximately 60 C.). The product obtained (71.0 g.), which melts at 200 C., is dissolved in methylene chloride (1, 500 cc.) and the solution is filtered through silica gel (71.0 g.) contained in a column of diameter 5.8 cm. Elution is carried out using methylene chloride (4, 000 cc.). This elude is discarded. Elution is then carried out using methylene chloride (2, 000 cc.), a mixture of methylene chloride and methanol (99.5-0.5 by volume; 2, 000 cc.) and then a mixture of methylene chloride and methanol (99-1 volume; 6, 000 cc.). These eluates are combined and evaporated to dryness under reduced pressure (20 mm.Hg). The residue (51.0 g.) is purified by recrystallisation from acetonitrile (850 cc.). 5-(4-t.-Butoxycarbonylpiperazin-1-yl)carbonyloxy-6-(7-chloro-1, 8-naphthyridin-2-yl)-7-oxo-2, 3, 6, 7-tetrahydro-5H-1, 4-dithiino[2, 3-c]pyrrole (38.0 g.), which melts at 242 C., a compound of general formula I, is obtained. 6-(7-Chloro-1, 8-naphthyridin-2-yl)-5-hydroxy-7-oxo-2, 3, 6, 7-tetrahydro-5H-1, 4-dithiino[2, 3-c]pyrrole can be prepared in the following manner: Preparation of 2-Amino-7-hydroxy-l, 8-naphthyridine (10'g, 62'mmol) was ground to a fine powder and added to concentrated sulfuric acid (80'mL), and then sodium nitrite (5'g, 74'mmol) was added. The mixture was allowed to stand for 10'min, poured over crushed ice, and allowed to stand for 10'min. Excess acid was neutralized with sodium carbonate, and then the solution was acidified with glacial acetic acid (pH?=?3), giving 2, 7-dihydroxy-1, 8-naphthyridine as a brown powder. Yield?=?8'g (80%). 1H NMR (500'MHz, DMSO-d6): delta?=?7.54 (d, J?=?8.9'Hz, 2H), 5.98 (d, J?=?9.1'Hz, 2H), 3.31'ppm (brs, 2H); 13C NMR (126'MHz; DMSO-d6): delta?=?166.2, 149.8, 139.4, 112.6, 102.0'ppm; MS (ESI; CH3OH): m/z 163.05 ([M+H]+).

Molecular Weight:161.16
XLogP3:0.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Exact Mass:161.058911855
Monoisotopic Mass:161.058911855
Topological Polar Surface Area:68
Heavy Atom Count:12
Complexity:226
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes