A. Kamal et al. / Bioorg. Med. Chem. 19 (2011) 7136–7150
7147
4H-1,2,4-benzothiadiazine 1,1-dioxide (11a, 158 mg, 0.7 mmol) to
obtain the pure product 5b as a white solid. Yield 65%; mp 250–
254 °C; 1H NMR (200 MHz, CDCl3+DMSO-d6): d 9.99 (s, 1H),
8.46(d, J = 7.8 Hz, 1H), 8.28(d, J = 3.9 Hz, 1H), 8.08 (d, J = 7.8 Hz,
1H), 7.91–7.72 (m, 1H); 7.66–7.31 (m, 4H), 6.94–6.79 (m, 1H),
3.89 (s,3H); MS (ESI): m/z 459 [M+1]+; HRMS (ESI m/z) for
C
(
20H15Cl2N6O2S, calcd 473.0349, found 473.0354 [M+1]+; IR (KBr)
m
max/cmÀ1): 3290, 3198, 3106, 1594, 1562, 1439, 1339, 1311,
1174, 763; Anal. Calcd for C20H14Cl2N6O2S: C, 50.75; H, 2.98; N,
17.75. Found: C, 50.71; H, 2.99; N, 17.71.
4.2.28. 2-[2-(4-Methoxyphenyl)-3-pyridyl]-10-phenyl-5,10-
dihydro-5k6-benzo[e][1,2,4]triazolo [1,5-b][1,2,4]thiadiazine-
5,5-dione (5f)
C
(
20H14N6O2,F3S calcd 459.0836, found 459.0851 [M+1]+; IR (KBr)
m
max/cmÀ1): 3425, 3316, 3148, 1646, 1587, 1563, 1523, 1441,
1355, 1186, 756; Anal. Calcd for C20H13F3N6O2S: C, 52.40; H,
2.86; N, 18.33. Found: C, 52.35; H, 2.83; N, 18.30.
The compound 5f was prepared according to the method de-
scribed for compound 5a, employing 2-(4-methoxy phenylami-
no)nicotinic acid (9a, 244 mg, 1 mmol) and 3-hydrazino-4-
phenyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (11b, 201 mg,
0.7 mmol)to obtain the pure product 11f as a white solid. Yield
65%; mp 223–234 °C; 1H NMR (300 MHz, CDCl3): d 9.70 (br s,
1H), 8.34 (dd, J = 7.7, 1.9 Hz, 1H), 8.24 (dd, J = 4.7, 1.9 Hz, 1H),
8.18 (dd, J = 8.1, 1.5 Hz, 1H), 7.76–7.68 (m, 3H), 7.63–7.49 (m,
1H), 7.41 (t, J = 8.9 Hz, 3H), 6.84 (d, J = 8.9 Hz, 3H), 6.72–6.65 (m,
1H), 3.81 (s, 3H); MS (ESI): m/z 497 [M+1]+; HRMS (ESI m/z) for
C26H21N6O3S, calcd 497.1382, found 497.1396 [M+1]+; IR (KBr)
4.2.25. 2-(2-Anilino-3-pyridyl)-10-methyl-5,10-dihydro-5k6-
benzo[e][1,2,4]triazolo[1,5-b][1,2,4]thiadiazine-5,5-dione (5c)
The compound 5c was prepared according to the method de-
scribed for compound 5a, employing 2-(phenyl amino)nicotinic
acid (9c, 214 mg, 1 mmol) and 3-hydrazino-4-methy-4H-1,2,4-
benzothiadiazine 1,1-dioxide (11a, 158 mg, 0.7 mmol) to obtain
the pure product 5c as a white solid. Yield 62%; mp 246–248 °C;
1H NMR (200 MHz, CDCl3 +DMS0-d6): dd 9.91(br s, 1H), 8.51 (dd,
J = 7.5, 1.7 Hz, 1H), 8.32 (dd, J = 5.0, 1.7 Hz, 1H), 8.17 (dd, J = 8.3,
1.7 Hz, 1H), 7.86 (dt, J = 8.3, 6.6 Hz, 1H), 7.75 (d, J = 7.5 Hz, 3H),
7.52–7.44 (m, 2H), 7.35 (t, J = 8.3 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H),
6.90–6.81 (m, 1H), 3.97 (s, 3H); 13C NMR (75 MHz, DMSO-d6) d
156.2, 154.7, 151.7, 139.9, 138.9, 131.8, 131.7, 128.6, 122.0,
120.0, 119.5, 119.4, 119.3, 115.1, 113.6, 110.7, 105.0, 55.6; MS
(ESI): m/z 405 [M+1]+; HRMS (ESI m/z) for C20H17N6O2S, calcd
(m
max/cmÀ1): 3325, 3143, 2920, 1594, 1508, 1444, 1355, 1232,
1165, 765; Anal. Calcd for C26H20N6O3S: C, 62.89; H, 4.06; N,
16.93. Found: C, 62.84; H, 4.04; N, 16.92.
4.2.29. 10-Phenyl-2-[2-(3,4,5-trifluoroanilino)-3-pyridyl]-
5,10-dihydro-5k6-benzo[e] [1,2,4]triazolo[1,5-
b][1,2,4]thiadiazine-5,5-dione (5g)
405.1123, found 405.1133 [M+1]+; IR (KBr) (
m
max/cmÀ1): 3310,
The compound 5 g was prepared according to the method de-
scribed for compound 5a, employing 2-(3,4,5-trifluoro phenylami-
no)nicotinic acid (9b, 252 mg, 1 mmol) and 3-hydrazino-4-phenyl-
4H-1,2,4-benzothiadiazine 1,1-dioxide (11b, 201 mg, 0.7 mmol) to
obtain the pure product 5 g as a white solid. Yield 70%; mp 290–
293 °C charred; 1H NMR (200 MHz, CDCl3+DMSO-d6): d 10.21(s,
1H), 8.47–8.37 (m, 1H), 8.32–8.22 (m, 1H), 8.20–8.08 (m, 1H),
7.83–7.40 (m, 8H); 7.12–6.98 (m, 1H), 6.89–6.76 (m, 1H); MS
(ESI): m/z 521 [M+1]+; HRMS (ESI m/z) for C25H16F3N6O2S, calcd
3218, 3143, 3025, 1630, 1585, 1562, 1497, 1445, 1392, 1346,
1178, 1127, 760; Anal. Calcd for C20H16N6O2S: C, 59.39; H, 3.99;
N, 20.78. Found: C, 59.45; H, 3.96; N, 20.75.
4.2.26. 2-[2-(4-Chloroanilino)-3-pyridyl]-10-methyl-5,10-
dihydro-5k6-benzo[e][1,2,4]triazolo[1,5-b][1,2,4]thiadiazine-
5,5-dione (5d)
The compound 5d was prepared according to the method de-
scribed for compound 11a, employing 2-(4-chloro phenylamino)
nicotinic acid (9e, 249 mg, 1 mmol and 3-hydrazino-4-methy-4H-
1,2,4-benzothiadiazine 1,1-dioxide (10a, 158 mg, 0.7 mmol) to ob-
tain the pure product 5d as a white solid. Yield 64%; mp 218–
220 °C; 1H NMR (200 MHz, CDCl3) d 9.93 (br s, 1H), 8.52 (dd,
J = 7.7, 2.6 Hz, 1H), 8.32 (dd, J = 5.1, 2.6 Hz, 1H), 8.14 (d,
J = 7.7 Hz, 1H), 7.86 (t, J = 9.0 Hz, 1H), 7.74 (d, J = 9.0 Hz, 2H),
7.52–7.38 (m, 2H), 7.28 (d, J = 9.0 Hz, 2H), 6.86 (dd, J = 7.7, 5.1 Hz,
1H), 3.97 (s, 3H); MS (ESI): m/z 439 [M+1]+; HRMS (ESI m/z) for
521.1001, found 521.1008 [M+1]+; IR (KBr) (
m
max/cmÀ1): 3423,
3315, 3143, 1644, 1587, 1564, 1525, 1440, 1355, 1186, 757 cmÀ1
;
Anal. Calcd forC25H15F3N6O2S: C, 57.69; H, 2.90; N, 16.15. Found:
C, 57.62; H, 2.93; N, 16.17.
4.2.30. 2-(2-Anilino-3-pyridyl)-10-phenyl-5,10-dihydro-5k6-
benzo[e] [1,2,4]triazolo[1,5-b][1,2,4]thiadiazine-5,5-dione (5h)
The compound 5h was prepared according to the method de-
scribed for compound 5a, employing 2-(phenyl amino)nicotinic acid
(9c, 214 mg, 1 mmol) and 3-hydrazino-4-phenyl-4H-1,2,4-benzo-
thiadiazine 1,1-dioxide (11b, 201 mg, 0.7 mmol) to obtain the pure
product 11h as a white solid. Yield 66%; mp 233–234 °C charred;
1H NMR (300 MHz, CDCl3): d 9.96 (br s, 1H), 8.40 (dd, J = 8.3,
2.3 Hz, 1H), 8.29 (dd, J = 5.3, 2.3 Hz, 1H), 8.19 (dd, J = 7.5, 1.5 Hz,
1H), 7.78–7.70 (m, 3H), 7.66–7.39 (m, 6H), 7.31–7.25 (m, 3H), 6.98
(t, J = 8.3 Hz, 1H), 6.87 (d, J = 8.3 Hz, 1H), 6.79–6.71 (m, 1H); 13C
NMR (75 MHz, CDCl3): d 161.1, 153.3, 152.5, 150.1, 140.5, 137.6,
137.3, 136.3, 134.7, 130.9, 130.3, 129.0, 128.6, 124.6, 124.1, 121.8,
119.7, 117.3, 113.6, 107.9; MS (ESI): m/z 467 [M+1]+; HRMS (ESI
m/z) for C25H19N6O2S, calcd 467.1271, found 467.1290 [M+1]+; IR
C
(
20H16ClN6O2S, calcd 439.0742, found 439.0743 [M+1]+; IR (KBr)
m
max/cmÀ1): 3311, 3215, 3133, 1589, 1490, 1441, 1354, 1308,
1178, 823, 759, 603; Anal. Calcd for C20H15ClN6O2S: C, 54.73; H,
3.44; N, 19.15. Found: C, 54.68; H, 3.42; N, 19.16.
4.2.27. 2-[2-(2,4-Dichloroanilino)-3-pyridyl]-10-methyl-5,10-
dihydro-5k6-benzo[e][1,2,4]triazolo [1,5-b][1,2,4]thiadiazine-
5,5-dione (5e)
The compound 5e was prepared according to the method de-
scribed for compound 5a, employing 2-(2,4-dichloro phenylami-
no)nicotinic acid (7 g, 283 mg, 1 mmol) and 3-hydrazino-4-
methy-4H-1,2,4-benzothiadiazine1,1-dioxide
(10a,
158 mg,
(KBr) (m
max/cmÀ1): 3326, 3216, 3138, 3049, 2923, 1562, 1493,
0.7 mmol) to obtain the pure product 5e as a white solid. Yield
76%; mp 260–262 °C Charred; 1H NMR (200 MHz, CDCl3+DMSO-
d6): d 10.49 (br s, 1H), 8.95 (d, J = 8.7 Hz, 1H), 8.62 (dd, J = 7.7,
1.9 Hz, 1H), 8.46 (dd, J = 4.8, 1.9 Hz, 1H), 8.27 (d, J = 8.7 Hz, 1H),
8.02 (t, J = 8.7 Hz, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.64–7.58 (m, 2H),
7.42 (dd, J = 8.7, 1.9 Hz, 1H), 7.14 (dd, J = 7.7, 4.9 Hz, 1H), 4.02 (s,
3H); 13C NMR (75 MHz, CF3COOD): d 160.4, 156.5, 151.9, 151.7,
147.9, 140.2, 139.1, 138.7, 138.6, 135.6, 133.8, 131.8, 131.7,
130.4, 127.1, 126.7, 122.5, 118.7, 116.8, 116.3, 115., 111.3, 111.0,
36.04; MS (ESI): m/z 473 [M+1]+; HRMS (ESI m/z) for
1438, 1349, 1183, 751, 696, 659;. Anal. Calcd for C25H18N6O2S: C,
64.36; H, 3.89; N, 18.01. Found: C, 64.43; H, 3.86; N, 18.02.
4.2.31. 2-[2-(4-Chloroanilino)-3-pyridyl]-10-phenyl-5,10-
dihydro-5k6-benzo[e][1,2,4]triazolo[1,5-b][1,2,4]thiadiazine-
5,5-dione (5i)
The compound 5i was prepared according to the method de-
scribed for compound 11a, employing 2-(4-chlorophenylamino)
nicotinic acid (9e, 249 mg, 1 mmol and 3-hydrazino-4-phenyl-4H-
1,2,4-benzothiadiazine 1,1-dioxide (11b, 201 mg, 0.7 mmol) to