Med Chem Res (2012) 21:1403–1410
1407
quinolone), 4.4–4.6 (d, 2H, OCH2 oxazine), 3.2–3.4 (m,
1H, CH oxazine), 2.3 (s, 3H, N–CH3), 1.2 (d, 3H, CH3
oxazine). IR mmax cm-1 (KBr): 3068.85, 3045.27, 1047.38,
1616.40, 1587.47, 750.33. MS: 498.60 (M?, 100%).
(KBr): 3068.85, 3045.27, 1047.38, 1616.40 (C=O), 1587.47.
MS: 489.37 (M?, 100%).
9-Fluoro-3,7-dihydro-3-methyl-6-(N0-
methylenebenzohydrazide) 10-(4-methyl piperazin-1-yl)-
2H-[1,4]oxazino[2,3,4-ij]quinolin-7-one (3f)
9-Fluoro-3,7-dihydro-3-methyl-6-(4-methoxy-N-
methylenebenzohydrazide)10-(4-methylpiperazin-1-yl)-2H-
[1,4]oxazino[2,3,4-ij]quinolin-7-one (3b)
1
Yield: 59%. m.p. 200–203°C. H NMR (DMSO-d6) d :8.9
(s, 1H, NH (CONH)), 8.1 (d, 1H, N=CH),7.5 (m, 4H, Ar–H
benzene), 7.9 (s, 8H, CH2 piperazine), 7.7 (m, 1H, Ar–H
quinolone), 4.4–4.6 (d, 2H, OCH2 oxazine), 3.2–3.4 (m,
1H, CH oxazine), 2.3 (s, 3H, N–CH3) 1.2 (d, 3H, CH3
oxazine). IR mmax cm-1 (KBr): 3068.85, 3045.27, 1047.38,
1616.40, 1587.47. MS: 464.13 (M?, 100%).
1
Yield: 42%. m.p. 176–179°C. H NMR (DMSO-d6) d: 8.9
(s, 1H, NH–CONH), 8.1 (d, 1H, N=CH), 7.5 (m, 4H, Ar–
H), 7.9 (s, 8H, CH2 piperazine), 7.7 (m, 1H, Ar–H), 6.8 (d,
1H, Ar–H), 4.4–4.6 (d, 2H, OCH2), 3.73 (s, 3H, OCH3),
3.2–3.4 (m, 1H, CH oxazine), 2.3 (s, 3H, N–CH3), 1.2 (d,
3H, CH3 oxazine). IR mmax cm-1 (KBr): 3068.85, 3045.27,
1047.38, 1616.40, 1587.47. MS: 494.51 (M?, 100%).
Synthesis of 9-fluoro-2,3-dihydro-6-(4,5-dihydro-5-thioxo-
1,3,4-oxadiazol-2-yl)-3-methyl-1,10-(4-methylpiperazin-1-
yl)-[1,4]oxazino[2,3,4-ij]quinolin-7-one (4)
9-Fluoro-3,7-dihydro-3-methyl l-6-(2-hydroxy-N0-
methylenebenzohydrazide)10-(4-methylpiperazin-1-yl)-2H-
[1,4]oxazino[2,3,4-ij]quinolin-7-one (3c)
To a solution containing ethanol (20 ml) and potassium
hydroxide (0.28 g, 5 mmol), the hydrazide (1.87 g,
5 mmol) was added. After solution has occurred, carbon
disulphide (0.42 g, 5.51 mmol) was added and the mixture
was stirred at room temperature for 14 h. After concen-
tration of the solution to a small volume, the residue was
dissolved in water (10 ml).A precipitate was obtained by
adding the solution to ice containing concentrated hydro-
chloric acid. The solid was filtered under suction and re-
crystallized with ethanol.
1
Yield: 55%. m.p. 196–199°C. H NMR (DMSO-d6) d: 12
(s, 1H, OH), 8.9 (s, 1H, NH (CONH)), 8.1 (d, 1H, N=CH),
7.5 (m, 4H, ArH), 7.9 (s, 8H, CH2 piperazine), 7.7 (m, 1H,
Ar–H), 5.1 (s, 1H, OH), 4.4–4.6 (d, 2H, OCH2 oxazine),
3.2–3.4 (m, 1H, CH oxazine), 2.3 (s, 3H, N–CH3), 1.2 (d,
3H, CH3 oxazine). IR mmax cm-1 (KBr): 3435.78, 3068.85,
3045.2, 3007.12, 1047.38, 1616.40, 1587.47.MS: 480.18
(M?, 100%).
1
Yield: 62%. m.p. 228–231°C. H NMR (DMSO-d6) d:
7.7 (m, 1H, Ar–H quinolone),7.9 (s, 8H, CH2 piperazine), 7
(s, 1H, NH oxadiazole), 2.1 (s, 3H, N–CH3), 4.4–4.6 (d,
2H, OCH2 oxazine), 3.2–3.4(m, 1H, CH oxazine), 1.3 (d,
3H, CH3 oxazine). IR mmax cm-1 (KBr): 3406.40, 3041.84,
1624.12, 1207.48, 1055.10, 979.87. MS: 416.44 (M?,
100%).
9-Fluoro-3,7-dihydro-3-methyl l-6-(N0-methylene-hydroxy-
2-carbohydrazide)10-(4-methylpiperazin-1-yl)-2H-
[1,4]oxazino[2,3,4-ij]quinolin-7-one (3d)
1
Yield: 45%. m.p. 172–175°C. H NMR (DMSO-d6) d: 8.9
(s, 1H, NH(CONH)), 8.1 (d, 1H, N=CH), 7.5 (m, 4H, Ar–
H),7.9 (s, 8H, CH2 piperazine),7.7 (m, 1H, Ar–H), 4.4–4.6
(d, 2H, OCH2 oxazine), 3.2–3.4 (m, 1H, CHoxazine), 2.3(s,
3H, N–CH3), 1.2 (d, 3H, CH3 oxazine). IR mmax cm-1
(KBr):3068.85, 3045.27, 1047.38, 1616.40, 1587.47. MS:
442.38 (M?, 100%).
Synthesis of 9-fluoro-2, 3-dihydro-6-[3-(4-Amino -5-
thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)]-3-methyl-10-
(4-methylpiperazin-1-yl)-[1,4]oxazino[2,3,4-ij]quinolin-
7-one (5)
A solution of compound 4 (1.42 g, 3.42 mmol), water
(3 ml) and 95% hydrazine hydrate (0.12 g, 2.42 mmol)
was heated under reflux for 14 h. After cooling, the solu-
tion was diluted with coldwater (20 ml), acidified by drop
wise addition of concentrated HCl and filtered. The solid
was washed with a minimum of cold water and recrystal-
lized from 1:1 ethanol:water.
Yield: 41%. m.p. 256–259°C. 1H NMR (DMSO-d6)
d:7.7 (m, 1H, Ar–H quinolone), 7 (s, 1H, NH),6.9 (s, 2H,
N–NH2), 7.9 (s, 8H, CH2 piperazine), 4.4–4.6 (d, 2H,
OCH2 oxazine), 3.2–3.4 (m, 1H, CH oxazine), 2.3 (s, 3H,
9-Fluoro-3,7-dihydro-3-methyl-6-(N0-methylene-3-
nitrobenzohydrazide) 10-(4-methyl piperazin-1-yl)-2H-
[1,4]oxazino[2,3,4-ij]quinolin-7-one (3e)
Yield: 56%. m.p. 208–211°C. 1H NMR (DMSO-d6) d:
8.6(m, 1H, Ar–H), 8.9(s, 1H, NH(CONH)), 8.1 (d, 1H,
N=CH), 7.5(m, 4H, Ar–H benzene), 7.9(s, 8H, CH2
piperazine), 7.7(m,1H, Ar–H quinolone), 4.4–4.6 (d, 2H,
OCH2 of oxazine), 3.2–3.4 (m, 1H, CH of oxazine), 2.3
(s, 3H, NCH3), 1.2 (d, 3H, CH3 of oxazine). IR mmax cm-1
123