Efficient Synthesis of Novel 3-(5-(2-Hydroxy-2-Phenylethylsulfonyl)-4- Phenyl-4H-1,2,4-Triazol-3-yl)-1,8-Naphthyridin-4(1H)-Ones

The reaction of 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbohydrazide (4) with substituted phenyl isothiocyanates (5) in ethanol under reflux for 30 min gave thiosemicarbazide derivatives 6, which on cyclization in 2N NaOH under refluxing conditions for 1h resulted in 3-(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (7). Alternatively, 7 could also be prepared from 4 through intermediacy of 8, i.e. 4 → 8 → 7. In another sequence of reactions, condensation of 7 with α-bromoacetylbenzene (10) in DMF and K2CO3 as base at 120°C for 2h gave 3-[5-(2-oxo-2- phenyl-ethylsulfanyl)-4-phenyl-4H-[1,2,4]triazol-3-yl]-1H-[1,8]naphthyridin-4-one (11). The latter, on oxidation with H2O2 in acetic acid at 100°C for 6h resulted in 3-[5-(2-oxo-2-phenyl-ethanesulfonyl)-4-phenyl-4H-[1,2,4]triazol-3-yl]-1H- [1,8]naphthyridin-4-one (12) which on reduction with NaBH4 in methanol at RT for 30 min yielded 3-(5-(2-hydroxy-2- phenylethylsulfonyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (13). Alternatively, 13 could also be prepared by reducing 11 using NaBH4 in methanol at RT for 30 min giving 3-(5-(2-hydroxy-2-phenylethylthio)-4-phenyl- 4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one(14) followed by oxidation with H2O2 in acetic acid at 100°C for 6h.