5324
V. Padmavathi et al. / European Journal of Medicinal Chemistry 46 (2011) 5317e5326
199e201 ꢁC; IR (KBr): 3281 (NH), 1674 (CONH), 1624 (C]N) cmꢀ1
1H NMR (DMSO-d6, 400 MHz):
JMX ¼ 11.1 Hz), 4.02 (dd, 1H, HM, JAM ¼ 11.6 Hz, JMX ¼ 11.1 Hz), 4.43
(dd, 1H, HA, JAM ¼ 11.6 Hz, JAX ¼ 6.1 Hz), 7.09e7.68 (m, 11H, AreH
and C5eH), 8.41 (bs, 1H, COeNH), 8.98 (bs, 1H, NeNH) ppm; 13C
;
JAX ¼ 6.0 Hz, JMX ¼ 11.3 Hz), 4.23 (dd, 1H, HM, JAM ¼ 11.5 Hz,
JMX ¼ 11.3 Hz), 4.41 (dd, 1H, HA, JAM ¼ 11.5 Hz, JAX ¼ 6.0 Hz),
7.08e7.73 (m, 10H, AreH and C5eH), 8.51 (bs, 1H, COeNH), 8.83 (bs,
0
d 48.2 (C4 ), 56.8
d
3.60 (dd, 1H, HX, JAX ¼ 6.1 Hz,
1H, NeNH) ppm; 13C NMR (DMSO-d6, 100 MHz):
0
0
(C5 ), 104.2 (C5), 142.3 (C3 ), 150.2 (C4), 164.8 (C2), 167.5 (C]O), 127.7,
128.5, 128.7, 129.1, 129.6, 131.5, 135.0, 136.5 (aromatic carbons)
ppm; Anal. Calcd. for C19H15ClN4OS: C, 59.60; H, 3.94; N, 14.63;
Found: C, 59.67; H, 3.92; N, 14.60%.
0 0
d 48.3 (C4 ), 58.8 (C5 ), 139.2 (C5), 141.3
NMR (DMSO-d6, 100 MHz):
0
(C4), 142.2 (C3 ), 151.2 (C2), 153.5 (C]O), 125.9, 126.8, 128.3, 130.3,
133.8,139.5 (aromatic carbons) ppm; Anal. Calcd. for C19H16N4O2: C,
68.66; H, 4.85; N, 16.85; Found: C, 68.72; H, 4.84; N, 16.89%.
5.1.3.7. 40,50-Dihydro-40-phenyl-N-(4-phenyl-1H-imidazol-2-yl)-10H-
5.1.3.2. 40,50-Dihydro-40-phenyl-N-(4-p-tolyloxazol-2-yl)-10H-pyr-
pyrazole-30-carboxamide (12a). Pale yellow solid (0.63 g, 77%); m.p.
azole-30-carboxamide (10b). Pale yellow solid (0.64 g, 75%); m.p.
222e224 ꢁC; IR (KBr): 3243 (NH), 1684 (CONH), 1594 (C]N) cmꢀ1
;
216e218 ꢁC; IR (KBr): 3275 (NH), 1671 (CONH), 1619 (C]N) cmꢀ1
;
1H NMR (DMSO-d6, 400 MHz):
d
3.66 (dd, 1H, HX, JAX ¼ 6.4 Hz,
1H NMR (DMSO-d6, 400 MHz):
d
2.31 (s, 3H, AreCH3), 3.58 (dd, 1H,
JMX ¼ 11.3 Hz), 4.11 (dd, 1H, HM, JAM ¼ 11.5 Hz, JMX ¼ 11.3 Hz), 4.40
(dd, 1H, HA, JAM ¼ 11.5 Hz, JAX ¼ 6.4 Hz), 7.19e7.70 (m, 11H, AreH
and C5eH), 8.02 (bs, 1H, COeNH), 8.13 (bs, 1H, NeNH), 11.21 (bs, 1H,
HX, JAX ¼ 6.0 Hz, JMX ¼ 11.0 Hz), 4.00 (dd, 1H, HM, JAM ¼ 11.5 Hz,
JMX ¼ 11.0 Hz), 4.39 (dd, 1H, HA, JAM ¼ 11.5 Hz, JAX ¼ 6.0 Hz),
7.06e7.70 (m, 10H, AreH and C5eH), 8.38 (bs, 1H, COeNH), 8.92 (bs,
C5eNH) ppm; 13C NMR (DMSO-d6, 100 MHz):
d
48.6 (C4 ), 59.1 (C5 ),
0
0
1H, NeNH) ppm; 13C NMR (DMSO-d6, 100 MHz):
d
24.2 (AreCH3),
0
119.7 (C5), 134.2 (C2), 141.0 (C4), 143.2 (C3 ), 153.5 (C]O), 127.5,
128.3, 129.5, 130.0, 133.0, 136.5 (aromatic carbons) ppm; Anal.
Calcd. for C19H17N5O: C, 68.86; H, 5.16; N, 21.13; Found: C, 68.81; H,
5.18; N, 21.24%.
0
0
0
48.1 (C4 ), 58.5 (C5 ), 139.0 (C5), 140.8 (C4), 142.0 (C3 ), 150.0 (C2),
153.2 (C]O), 125.7, 126.3, 127.8, 128.5, 130.1, 130.8, 138.3, 139.7
(aromatic carbons) ppm; Anal. Calcd. for C20H18N4O2: C, 69.34; H,
5.23; N, 16.17; Found: C, 69.38; H, 5.26; N, 16.11%.
5.1.3.8. 40,50-Dihydro-40-phenyl-N-(4-p-tolyl-1H-imidazol-2-yl)-10H-
5.1.3.3. N-(4-(p-Chlorophenyl)oxazol-2-yl)-40,50-dihydro-40-phenyl-
10H-pyrazole-30-carboxamide (10c). Pale yellow solid (0.74 g, 81%);
m.p. 224e226 ꢁC; IR (KBr): 3288 (NH), 1677 (CONH), 1628 (C]N)
pyrazole-30-carboxamide (12b). Pale yellow solid (0.64 g, 75%); m.p.
241e243 ꢁC; IR (KBr): 3237 (NH), 1681 (CONH), 1582 (C]N) cmꢀ1
;
1H NMR (DMSO-d6, 400 MHz):
d 2.31 (s, 3H, AreCH3), 3.64 (dd, 1H,
cmꢀ1
;
1H NMR (DMSO-d6, 400 MHz):
d
3.62 (dd, 1H, HX,
HX, JAX ¼ 6.7 Hz, JMX ¼ 11.4 Hz), 4.09 (dd, 1H, HM, JAM ¼ 11.4 Hz,
JMX ¼ 11.4 Hz), 4.41 (dd, 1H, HA, JAM ¼ 11.4 Hz, JAX ¼ 6.7 Hz),
7.06e7.65 (m, 10H, AreH and C5eH), 8.00 (bs, 1H, COeNH), 8.11 (bs,
1H, NeNH), 11.19 (bs, 1H, C5eNH) ppm; 13C NMR (DMSO-d6,
JAX ¼ 6.2 Hz, JMX ¼ 11.2 Hz), 4.08 (dd, 1H, HM, JAM ¼ 11.7 Hz,
JMX ¼ 11.2 Hz), 4.47 (dd, 1H, HA, JAM ¼ 11.7 Hz, JAX ¼ 6.2 Hz),
7.07e7.71 (m, 10H, AreH and C5eH), 8.42 (bs, 1H, COeNH), 9.00 (bs,
0
1H, NeNH) ppm; 13C NMR (DMSO-d6, 100 MHz):
d
48.5 (C4 ), 58.9
100 MHz):
d
24.0 (AreCH3), 47.3 (C4 ), 58.2 (C5 ), 119.1 (C5), 133.1
0
0
0
0
0
(C5 ),139.5 (C5),141.4 (C4),142.7 (C3 ),150.5 (C2),153.9 (C]O),126.0,
127.4, 127.8, 128.5, 129.3, 130.0, 137.5, 139.9 (aromatic carbons)
ppm; Anal. Calcd. for C19H15ClN4O2: C, 62.21; H, 4.12; N, 15.27;
Found: C, 62.17; H, 4.14; N, 15.32%.
(C2), 140.5 (C4), 143.0 (C3 ), 153.2 (C]O), 127.2, 127.5, 128.2, 128.9,
129.6, 135.8, 138.1 (aromatic carbons) ppm; Anal. Calcd. for
C20H19N5O: C, 69.54; H, 5.54; N, 20.27; Found: C, 69.60; H, 5.51; N,
20.36%.
5.1.3.4. 40,50-Dihydro-40-phenyl-N-(4-phenylthiazol-2-yl)-10H-pyr-
5.1.3.9. N-(4-(p-Chlorophenyl)-1H-imidazol-2-yl)-40,50-dihydro-40-
phenyl-10H-pyrazole-30-carboxamide (12c). Pale yellow solid
(0.66 g, 73%); m.p. 250e252 ꢁC; IR (KBr): 3245 (NH), 1688 (CONH),
azole-30-carboxamide (11a). Pale yellow solid (0.61 g, 71%); m.p.
213e215 ꢁC; IR (KBr): 3319 (NH), 1653 (CONH), 1592 (C]N) cmꢀ1
;
1H NMR (DMSO-d6, 400 MHz):
JMX ¼ 11.3 Hz), 4.21 (dd, 1H, HM, JAM ¼ 11.9 Hz, JMX ¼ 11.3 Hz), 4.38
(dd,1H, HA, JAM ¼ 11.9 Hz, JAX ¼ 6.1 Hz), 7.17e7.74 (m,11H, AreH and
C5eH), 8.48 (bs, 1H, COeNH), 8.81 (bs, 1H, NeNH) ppm; 13C NMR
d
3.58 (dd, 1H, HX, JAX ¼ 6.1 Hz,
1605 (C]N) cmꢀ1 1H NMR (DMSO-d6, 400 MHz):
; d 3.68 (dd, 1H,
HX, JAX ¼ 6.3 Hz, JMX ¼ 11.2 Hz), 4.16 (dd, 1H, HM, JAM ¼ 11.6 Hz,
JMX ¼ 11.2 Hz), 4.47 (dd, 1H, HA, JAM ¼ 11.6 Hz, JAX ¼ 6.3 Hz),
7.20e7.74 (m, 10H, AreH and C5eH), 8.08 (bs, 1H, NH), 8.25 (bs, 1H,
NeNH), 11.71 (bs, 1H, C5eNH) ppm; 13C NMR (DMSO-d6, 100 MHz):
0 0 0
d 47.8 (C4 ), 56.3 (C5 ), 103.6 (C5), 141.5 (C3 ),
(DMSO-d6, 100 MHz):
0
0
0
149.8 (C4), 164.2 (C2), 167.4 (C]O), 126.5, 127.6, 128.9, 129.8, 133.2,
139.0 (aromatic carbons) ppm; Anal. Calcd. for C19H16N4OS: C,
65.49; H, 4.62; N, 16.08; Found: C, 65.56; H, 4.60; N, 16.16%.
d 48.9 (C4 ), 59.1 (C5 ), 119.9 (C5), 134.6 (C2), 141.5 (C4), 143.6 (C3 ),
153.9 (C]O), 126.8, 127.3, 128.1, 129.4, 129.8, 131.3, 134.4, 136.2
(aromatic carbons) ppm; Anal. Calcd. for C19H16ClN5O: C, 62.38; H,
4.40; N, 19.14; Found: C, 62.32; H, 4.43; N, 19.20%.
5.1.3.5. 40,50-Dihydro-40-phenyl-N-(4-p-tolylthiazol-2-yl)-10H-pyr-
azole-30-carboxamide (11b). Pale yellow solid (0.71 g, 79%); m.p.
5.1.4. General procedure for synthesis of 40-phenyl-N-(4-aryloxazol-
2-yl)-10H-pyrazole-30-carboxamide (13aec)/40-phenyl-N-(4-
arylthiazol-2-yl)-10H-pyrazole-30-carboxamide (14aec)/40-phenyl-
N-(4-aryl-1H-imidazol-2-yl)-10H-pyrazole-30-carboxamide (15aec)
The compound 10/11/12 (1 mmol), chloranil (0.29 g, 1.2 mmol)
and xylene (10 ml) were refluxed for 24e25 h. Then, it was treated
with 5% NaOH solution. The organic layer was separated and
repeatedly washed with water and dried. The solvent was removed
in vacuo. The solid obtained was purified by recrystallization from
2-propanol.
230e232 ꢁC; IR (KBr): 3310 (NH), 1650 (CONH), 1580 (C]N) cmꢀ1
;
1H NMR (DMSO-d6, 400 MHz):
d 2.28 (s, 3H, AreCH3), 3.54 (dd, 1H,
HX, JAX ¼ 6.1 Hz, JMX ¼ 11.1 Hz), 4.18 (dd, 1H, HM, JAM ¼ 11.6 Hz,
JMX ¼ 11.1 Hz), 4.34 (dd, 1H, HA, JAM ¼ 11.6 Hz, JAX ¼ 6.1 Hz),
7.19e7.81 (m, 10H, AreH and C5eH), 8.46 (bs, 1H, COeNH), 8.80 (bs,
1H, NeNH) ppm; 13C NMR (DMSO-d6, 100 MHz):
d 24.5 (AreCH3),
0
0
0
47.2 (C4 ), 56.0 (C5 ), 102.0 (C5), 141.0 (C3 ), 149.1 (C4), 163.9 (C2),
166.3 (C]O), 125.8, 127.0, 128.2, 128.8, 129.7, 130.9, 137.7, 139.4
(aromatic carbons) ppm; Anal. Calcd. for C20H18N4OS: C, 66.27; H,
5.00; N, 15.45; Found: C, 66.32; H, 5.03; N, 15.50%.
5.1.4.1. 40-Phenyl-N-(4-phenyloxazol-2-yl)-10H-pyrazole-30-carbox-
5.1.3.6. N-(4-(p-Chlorophenyl)thiazol-2-yl)-40,50-dihydro-40-phenyl-
10H-pyrazole-30-carboxamide (11c). Pale yellow solid (0.76 g, 80%);
m.p. 237e239 ꢁC; IR (KBr): 3340 (NH), 1662 (CONH), 1601 (C]N)
amide (13a). White solid (0.21 g, 64%); m.p. 228e230 ꢁC; IR (KBr):
3242 (NH), 1643 (CONH), 1627 (C]C), 1578 (C]N) cmꢀ1 1H NMR
;
0
(DMSO-d6, 400 MHz):
d
6.24 (s, 1H, C5 eH), 6.61 (bs, 1H, NeNH),
cmꢀ1
;
1H NMR (DMSO-d6, 400 MHz):
d
3.59 (dd, 1H, HX,
6.82e7.63 (m,11H, AreH and C5eH), 8.52 (bs,1H, COeNH) ppm; 13
C