J. Gowda et al. / European Journal of Medicinal Chemistry 46 (2011) 4100e4106
4105
(benzothiazine C-2), 38.41 (C between triazole and benzothiazine),
(s, 1H, N]CH); 13C NMR (DMSO-d6):
d
23.30 (piperidine C-4), 25.40
50.04 (piperidine C-2 and C-6), 69.23 (C between piperidine and
triazole), 118.83 (benzothiazine C-6), 124.09 (benzothiazine C-7),
124.09 (benzothiazine C-8), 128.12 (benzothiazine C-5), 129.85
(benzothiazine C-10), 131.19 (benzothiazine C-9), 129.85 (phenyl C-
3 and C-5), 123.65 (phenyl C-2 and C-6), 137.99 (nitrophenyl C-4),
149.52 (nitrophenyl C-1), 145.55 (C]S), 160.22 (N¼CHR), 162.16
(N¼CRR), 165.14 (C]O). Direct-MS: m/z, 524.1, 427.3, 86.1 (Mþþ1).
(piperidine C-3 and C-5), 30.52 (benzothiazine C-2), 38.42 (C
between triazole and benzothiazine), 50.04 (piperidine C-2 and C-6),
69.23 (C between piperidine and triazole), 118.74 (benzothiazine C-
6), 123.46 (benzothiazine C-7), 123.67 (benzothiazine C-5), 127.07
(benzothiazine C-8), 128.10 (benzothiazine C-10), 130.89 (benzo-
thiazine C-9), 129.23 (chlorophenyl C-2 and C-6), 130.46 (chlor-
ophenyl C-3 and C-5), 137.42 (chlorophenyl C-4), 138.34
(chlorophenyl C-1),145.68 (C]S),162.42 (N¼CHR),162.64 (N¼CRR),
165.13 (C]O); Direct-MS:m/z, 513.2, 515.2, 416.1, 418.3, 86.2 (Mþþ1).
5.6.7. 4-{[1-N-methyl piperazinomethyl-4-(p-chloro-benzylidenea-
mino)-5-sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-2H-
1,4-benzothiazin-3(4H)-one 6g
5.6.10. 4-{[1-N-methyl piperazinomethyl-4-(p-hydroxy-benzylide-
neamino)-5-sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-
2H-1,4-benzothiazin-3(4H)-one 6j
IR (KBr)
(DMSO-d6):
g
/cmꢁ1: 1674 (C]O), 1575 (C]N), 1264 (C]S); 1H NMR
d
2.2 (s, 3H, N-CH3), 2.25 (t, 4H, CH2N-CH2), 2.58 (t, 4H,
CH2N-CH2), 3.55 (s, 2H, benzothiazine S-CH2), 4.99 (s, 2H, triazole
N-CH2), 5.42 (s, 2H, benzothiazine N-CH2), 7.01e7.05 (t, 1H,
J ¼ 7.4 Hz, benzothiazine 6eH), 7.22e7.27 (t, 1H, J ¼ 8.40 Hz, ben-
zothiazine 7eH), 7.34e7.36 (d, 2H, J ¼ 8.26 Hz, benzothiazine 5-H
and 8eH), 7.62e7.64 (m, 2H, J ¼ 8.36 Hz protons ortho to the
chloro group), 7.89e7.92 (d, 2H, J ¼ 8.48 Hz, protons meta to the
IR (KBr)
g
/cmꢁ1: 3549 (OH), 1676 (C]O), 1575 (C]N), 1265 (C]
S); 1H NMR (DMSO-d6):
d
2.1 (s, 3H, N-CH3), 2.23 (t, 4H, CH2N-CH2),
2.56 (t, 4H, CH2N-CH2), 3.56 (s, 2H, benzothiazine S-CH2), 4.99 (s,
2H, triazole N-CH2), 5.41 (s, 2H, benzothiazine N-CH2), 7.03e7.04 (t,
1H, J ¼ 7.2 Hz, benzothiazine 6eH), 7.24e7.26 (t, 1H, J ¼ 7.24 Hz,
benzothiazine 7eH), 7.36e7.39 (d, 2H, J ¼ 6.4 & 7.08 Hz, benzo-
thiazine 5-H and 8eH), 7.66e7.68 (t, 2H, J ¼ 7.2 Hz, protons meta to
the hydroxyl group), 6.85e6.87 (t, 2H, J ¼ 7.4 Hz, protons ortho to
the hydroxyl group), 9.82 (s, 1H, N]CH); 13C NMR (DMSO-d6):
chloro group), 9.93 (s, 1H, N]CH); 13C NMR (DMSO-d6):
d 30.42
(benzothiazine C-2), 38.82 (C between triazole and benzothiazine),
45.74 (N-CH3), 49.47 (N-methylpiperazine C-3 and C-5), 54.52 (N-
methylpiperazine C-2 and C-6), 68.38 (C between N-methylpiper-
azine and triazole), 118.74 (benzothiazine C-6), 123.46 (benzothia-
zine C-7), 123.67 (benzothiazine C-5), 127.07 (benzothiazine C-8),
128.10 (benzothiazine C-10), 130.89 (benzothiazine C-9), 129.23
(chlorophenyl C-2 and C-6), 130.46 (chlorophenyl C-3 and C-5),
137.42 (chlorophenyl C-4), 138.34 (chlorophenyl C-1), 145.68 (C]
S), 162.42 (N¼CHR), 162.64 (N¼CRR),165.13 (C]O). Direct-MS: m/z,
528.6, 530.6, 416.1, 418.3, 101.3 (Mþþ1).
d
30.42 (benzothiazine C-2), 38.80 (C between triazole and ben-
zothiazine), 45.74 (N-CH3), 49.44 (N-methylpiperazine C-3 and C-
5), 54.52 (N-methylpiperazine C-2 and C-6), 68.38 (C between N-
methylpiperazine and triazole), 118.71 (benzothiazine C-6), 123.41
(benzothiazine C-7), 123.65 (benzothiazine C-5), 127.07 (benzo-
thiazine C-8),128.07 (benzothiazine C-10),131.92 (benzothiazine C-
9), 129.02 (hydroxyphenyl C-3 and C-5), 129.24 (hydroxyphenyl C-2
and C-6), 137.08 (hydroxyphenyl C-4), 138.80 (hydroxyphenyl C-1),
145.70 (C]S), 162.45 (N¼CHR), 164.35 (N¼CRR), 165.13 (C]O);
Direct-MS: m/z, 510.5, 398.05, 101.2 (Mþþ1).
5.6.8. 4-{[1- morpholinomethyl-4-(p-chloro-benzylideneamino)-5-
sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-2H-1,4-
benzothiazin-3(4H)-one 6h
5.6.11. 4-{[1- morpholinomethyl-4-(p-hydroxy-benzylideneamino)-
5-sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-2H-1,4-
benzothiazin-3(4H)-one 6k
IR (KBr)
(DMSO-d6):
g
/cmꢁ1: 1679 (C]O), 1577 (C]N), 1260 (C]S); 1H NMR
d
2.52 (m, 4H, CH2N-CH2), 3.48 (t, 4H, CH2OCH2), 3.54
(s, 2H, benzothiazine S-CH2), 4.97 (s, 2H, triazole N-CH2), 5.41 (s,
2H, benzothiazine N-CH2), 7.00e7.05 (t, 1H, J ¼ 7.47 Hz, benzo-
thiazine 6eH), 7.20e7.25 (t, 1H, J ¼ 8.43 Hz, benzothiazine 7eH),
7.35e7.37 (d, 2H, J ¼ 8.2 Hz, benzothiazine 5-H and 8eH), 7.60e7.62
(m, 2H, J ¼ 8.46 Hz protons ortho to the chloro group), 7.91e7.94 (d,
2H, J ¼ 8.52 Hz, protons meta to the chloro group), 9.91 (s, 1H, N]
IR (KBr)
g
/cmꢁ1: 3540 (OH), 1676 (C]O), 1575 (C]N), 1265 (C]
S); 1H NMR (DMSO-d6):
d
2.52 (t, 4H, CH2N-CH2), 3.46 (t, 4H,
CH2OCH2), 3.53 (s, 2H, benzothiazine S-CH2), 4.99 (s, 2H, triazole N-
CH2), 5.41 (s, 2H, benzothiazine N-CH2), 7.03e7.05 (t,1H, J ¼ 7.34 Hz,
benzothiazine 6eH), 7.23e7.25 (t, 1H, J ¼ 7.26 Hz, benzothiazine
7eH), 7.35e7.38 (d, 2H, J ¼ 8.07 Hz, benzothiazine 5-H and 8eH),
7.67e7.68 (t, 2H, J ¼ 7.1 Hz, protons meta to the hydroxyl group),
6.85e6.86 (t, 2H, J ¼ 7.3 Hz, protons ortho to the hydroxyl group),
CH); 13C NMR (DMSO-d6):
d 30.44 (benzothiazine C-2), 38.82 (C
between triazole and benzothiazine), 50.04 (morpholine C-3 and C-
5), 65.96 (morpholine C-2 and C-6), 68.38 (C between morpholine
and triazole), 118.74 (benzothiazine C-6), 123.46 (benzothiazine C-
7), 123.67 (benzothiazine C-5), 127.07 (benzothiazine C-8), 128.10
(benzothiazine C-10), 130.89 (benzothiazine C-9), 129.23 (chlor-
ophenyl C-2 and C-6), 130.46 (chlorophenyl C-3 and C-5), 137.42
(chlorophenyl C-4), 138.32 (chlorophenyl C-1), 145.68 (C]S),
162.42 (N¼CHR), 162.64 (N¼CRR), 165.13 (C]O); Direct-MS: m/z,
515.3, 517.2, 416.1, 418.3, 88.2 (Mþþ1).
9.84 (s, 1H, N]CH); 13C NMR (DMSO-d6):
d 30.45 (benzothiazine C-
2), 38.80 (C between triazole and benzothiazine), 50.02 (morpholine
C-3 and C-5), 65.99 (morpholine C-2 and C-6), 68.39 (C between
morpholine and triazole), 118.71 (benzothiazine C-6), 123.41 (ben-
zothiazine C-7), 123.65 (benzothiazine C-5), 127.07 (benzothiazine
C-8), 128.07 (benzothiazine C-10), 131.92 (benzothiazine C-9),
129.04 (hydroxyphenyl C-3 and C-5), 129.26 (hydroxyphenyl C-2
and C-6), 137.06 (hydroxyphenyl C-4), 138.82 (hydroxyphenyl C-1),
145.68 (C]S), 162.45 (N¼CHR), 164.35 (N¼CRR), 165.13 (C]O);
Direct-MS: m/z, 496.7, 398.05, 88.2 (Mþþ1).
5.6.9. 4-{[1- piperidinomethyl-4-(p-chloro-benzylideneamino)-5-
sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-2H-1,4-
benzothiazin-3(4H)-one 6i
5.6.12. 4-{[1- piperidinomethyl-4-(p-hydroxy-benzylideneamino)-
5-sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-2H-1,4-
benzothiazin-3(4H)-one 6l
IR (KBr)
(DMSO-d6):
g
/cmꢁ1: 1679 (C]O), 1576 (C]N), 1260 (C]S); 1H NMR
d
1.22 (m, 2H, CH2), 1.36 (m, 4H, CH2CH2), 2.44 (t, 4H,
CH2N-CH2), 3.54 (s, 2H, benzothiazine S-CH2), 4.95 (s, 2H, triazole N-
CH2), 5.47 (s, 2H, benzothiazine N-CH2), 7.03e7.04 (t, 1H, J ¼ 7 Hz,
benzothiazine 6eH), 7.23e7.25 (t, 1H, J ¼ 7.22 Hz, benzothiazine
7eH), 7.35e7.37 (d, 2H, J ¼ 8.04 Hz, benzothiazine 5-H and 8eH),
7.61e7.63 (m, 2H, J ¼ 8.42 Hz protons ortho to the chloro group),
7.91e7.93 (d, 2H, J ¼ 8.52 Hz, protons meta to the chloro group), 9.92
IR (KBr)
g
/cmꢁ1: 3545 (OH), 1675 (C]O), 1579 (C]N), 1265 (C]
S); 1H NMR (DMSO-d6):
d
1.22 (m, 2H, CH2), 1.35 (m, 4H, CH2CH2),
2.43 (t, 4H, CH2N-CH2), 3.54 (s, 2H, benzothiazine S-CH2), 4.98 (s,
2H, triazole N-CH2), 5.41 (s, 2H, benzothiazine N-CH2), 7.04e7.05 (t,
1H, J ¼ 7 Hz, benzothiazine 6eH), 7.24e7.26 (t, 1H, J ¼ 7.2 Hz,
benzothiazine 7eH), 7.26e7.28 (d, 2H, J ¼ 8.06 Hz, benzothiazine 5-