A. Kamal et al. / Bioorg. Med. Chem. 14 (2006) 650–658
655
6.4. N0-(4-Methyl-1,1-dioxido-4H-1,2,4-benzothiadiazin-
3-yl)pyrazine-2-carbohydrazide (8c)
Yield 72%; mp 284–286 ꢁC; 1H NMR (400 MHz,
CDCl3 + DMSO-d6): d 10.6 (s, 1H), 9.3 (s, 1H), 8.8 (d,
1H, J = 2.2 Hz), 8.6 (s, 1H), 7.75 (d, 1H, J = 2.2 Hz),
7.55 (dd, 1H, J = 8.92 Hz, 2.2 Hz), 7.3 (d, 1H,
J = 8.9 Hz), 3.6 (s, 3H); FABMS m/z 367 (M++1, 60);
IR (KBr) (mmax/cmꢁ1) 3274, 3031, 2940, 1690, 1592,
1551, 1477, 1409, 1367, 1285, 1154, 1114. Anal. Calcd
for C13H11ClN6O3S: C, 42.57; H, 3.02; N, 22.91%.
Found: C, 42.54; H, 3.12; N, 22.58%.
The title compound was obtained from 3-hydrazino-4-
methyl-4H-1,2,4-benzothiadiazine
1,1-dioxide
(5a,
226 mg, 1 mmol), pyrazinoyl chloride (6c, 143 mg,
1 mmol) and triethyl amine (0.17 mL, 1.22 mmol) as de-
scribed in method A (yield 65%) or from 3-chloro-4-
methyl-4H-1,2,4-benzothiadiazine
231 mg, 1 mmol) and pyrazine-2-carbohydrazide (7c,
1,1-dioxide
(4a,
137 mg, 1 mmol) as described in method B (yield 70%).
6.8. N0-(4-Ethyl-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-
yl)nicotinohydrazide (8g)
Mp 266–268 ꢁC; 1H NMR (400 MHz, CDCl3 + DMSO-
d6): d 10.8 (s, 1H), 10.0 (br s, 1H), 9.2 (s, 1H), 8.8 (d, 1H,
J = 2.3 Hz), 8.7 (d, 1H, J = 2.3 Hz), 7.7 (d, 1H,
J = 7.6 Hz), 7.6 (t, 1H, J = 7.6 Hz), 7.35 (m, 2H), 3.65
The title compound was obtained from 3-chloro-4-ethyl-
4H-1,2,4-benzothiadiazine 1,1-dioxide (4b, 245 mg,
1 mmol) and nicotinic hydrazide (7a, 137 mg, 1 mmol)
as described in method B.
(s, 3H); FABMS m/z 333 (M++1, 60); IR (KBr) (mmax
/
cmꢁ1) 3357, 3085, 3009, 1711, 1592, 1546, 1505, 1475,
1374, 1291, 1176, 1097; Anal. Calcd for C13H12N6O3S:
C, 46.98: H, 3.64: N, 25.29%. Found: C, 46.61; H,
3.65; N, 25.34%.
Yield 78%; mp 184–186 ꢁC; 1H NMR (400 MHz,
CDCl3 + DMSO-d6): d 10.95 (s, 1H), 9.8 (br s, 1H),
9.2 (s, 1H), 8.7 (br s, 1H), 8.3 (d, 1H, J = 7.0 Hz), 7.8
(d, 1H, J = 7.0 Hz), 7.6 (m, 1H), 7.4 (m, 2H), 7.3 (t,
1H, J = 7.0 Hz) 4.2 (q, 2H, J = 7.0 Hz), 1.4 (t, 3H,
6.5. 6-Chloro-N0-(4-methyl-1,1-dioxido-4H-1,2,4-benzo-
thiadiazin-3-yl)nicotinohydrazide (8d)
J = 7.0 Hz); EIMS m/z 346 (M++1); IR (KBr) (mmax
/
cmꢁ1) 3205, 2990, 1664, 1594, 1532, 1391, 1282, 1170,
1100. Anal. Calcd for C15H15N5O3S: C, 52.16; H, 4.38;
N, 20.28%. Found: C, 52.24; H, 4.44; N, 20.32%.
The title compound was obtained from 3-hydrazino-4-
(5a,
methyl-4H-1,2,4-benzothiadiazine
1,1-dioxide
226 mg, 1 mmol), 6-chloro-nicotinoyl chloride (6d,
176 mg, 1 mmol) and triethyl amine (0.17 mL,
1.22 mmol) as described in method A. Yield 68%; mp
226–228 ꢁC; H NMR (400 MHz, CDCl3 + DMSO-d6):
6.9. N0-(4-Ethyl-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-
yl)isonicotinohydrazide (8h)
1
d 10.95 (s, 1H), 9.9 (br s, 1H), 9.0 (s, 1H), 8.3 (d, 1H,
J = 8.2 Hz), 7.7 (d, 1H, J = 8.2 Hz), 7.56 (t, 1H,
J = 8.2 Hz), 7.42 (m, 1H), 7.3 (m, 2H), 3.62 (s, 3H); FAB-
MS m/z 366 (M++1, 60); IR (KBr) (mmax/cmꢁ1) 3218,
3063, 2963, 1693, 1593, 1543, 1465, 1375, 1267, 1160,
1099; Anal. Calcd for C14H12ClN5O3S: C, 45.97; H,
3.31; N, 19.15%. Found: C, 45.97; H, 3.31; N, 19.15%.
The title compound was obtained from 3-chloro-4-ethyl-
4H-1,2,4-benzothiadiazine 1,1-dioxide (4b, 245 mg,
1 mmol) and isonicotinic hydrazide (7b, 137 mg,
1 mmol) as described in method B.
Yield 78%; mp 102–104 ꢁC; 1H NMR (200 MHz,
CDCl3 + DMSO-d6): d 11.0 (br s, 1H), 9.8 (br s, 1H),
8.8 (d, 2H, J = 5.07 Hz), 7.9 (d, 2H, J = 5.07 Hz) 7.6–
7.8 (m, 2H), 7.3–7.5 (m, 2H), 4.2 (q, 2H, J = 6.3 Hz),
1.45 (t, 3H, J = 6.3 Hz); FABMS m/z 344 (M+ꢁ1, 50).
Anal. Calcd for C15H15N5O3S: C, 52.16; H, 4.38; N,
20.28%. Found: C, 52.18; H, 4.32; N, 20.21%.
6.6. N0-(7-Chloro-4-methyl-1,1-dioxido-4H-1,2,4-benzo-
thiadiazin-3-yl)nicotinohydrazide (8e)
The title compound was obtained from 3,7-dichloro-4-
methyl-4H-1,2,4-benzothiadiazine
1,1-dioxide
265 mg, 1 mmol) and nicotinic hydrazide (7a, 137 mg,
(4e,
6.10. N0-(4-Ethyl-1,1-dioxido-4H-1,2,4-benzothiadiazin-
3-yl)pyrazine-2-carbohydrazide (8i)
1 mmol) as described in method B.
Yield 75%; mp 248 ꢁC (charred) 284–286 ꢁC (melted);
1H NMR (400 MHz, CDCl3 + DMSO-d6): d 11.0 (br s,
1H), 10.0 (br s, 1H), 9.2 (s, 1H), 8.8 (d, 1H,
J = 4.4 Hz), 8.3 (d, 1H, J = 8.1 Hz), 7.7 (s, 1H), 7.5
(m, 1H), 7.4 (m, 1H), 7.3 (dd, 1H, J = 8.8 Hz,
0.74 Hz), 3.6 (s, 3H); FABMS m/z 365 (M++1, 20).
Anal. Calcd for C14H12ClN5O3S: C, 45.97; H, 3.31; N,
19.15%. Found: C, 45.92; H, 3.28; N, 19.27%.
The title compound was obtained from 3-chloro-4-ethyl-
4H-1,2,4-benzothiadiazine 1,1-dioxide (4b, 245.0 mg,
1 mmol) and pyrazine-2-carbohydrazide (7c, 138 mg,
1 mmol) as described in method B (yield 70%) or from
3-hydrazino-4-ethyl-4H-1,2,4-benzothiadizine 1,1-diox-
ide (5b, 240 mg, 1 mmol) and pyrazinoyl chloride (6c,
143 mg, 1 mmol) and triethyl amine (0.167 mL,
1.2 mmol) as described in method A (yield 66%).
6.7. N0-(7-Chloro-4-methyl-1,1-dioxido-4H-1,2,4-benzo-
thiadiazin-3-yl)pyrazine-2-carbohydrazide (8f)
Mp 234–236 ꢁC; 1H NMR (400 MHz, CDCl3 + DMSO-
d6): d 10.6 (br s, 1H), 9.3 (s, 1H), 8.8 (d, 1H, J = 2.3 Hz),
8.7 (d, 1H, J = 2.3 Hz), 7.8 (d, 1H, J = 8.4 Hz), 7.6 (t,
1H, J = 8.4 Hz), 7.3 (m, 2H), 4.2 (q, 2H, J = 6.9 Hz),
1.4 (t, 3H, J = 6.9 Hz); EIMS m/z 346 (M+, 20); IR
(KBr) (mmax/ cmꢁ1) 3392, 3265, 3065, 2984, 1709, 1594,
1547, 1501, 1393, 1276, 1167. Anal. Calcd for
The title compound was obtained from 3,7-dichloro-4-
methyl-4H-1,2,4-benzothiadiazine
265 mg, 1 mmol) and pyrazine-2-carbohydrazide (7c,
1,1-dioxide
(4e,
138 mg, 1 mmol) as described in method B.