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V. Markovic et al. / Bioorganic Chemistry 39 (2011) 18–27
20
1279, 749. Anal. Calcd for C17H14N4O3 (322.32 g/mol): C, 63.35; H,
4.38; N, 17.38. Found: C, 63.66; H, 4.39; N, 17.43.
(s, 1H, C(@S)NH), 11.44 (bs, 1H, NH). 13C NMR (50 MHz, DMSO-
d6): d = 12.59, 106.37, 118.00, 124.55, 129.14, 138.69, 144.01,
150.06, 164.02, 181.66. IR (KBr disc, cmꢀ1): 3438, 3358, 3319,
3178, 1671, 1633, 1608, 1597, 1498, 1233, 1163, 1004, 756. Anal.
Calcd for C12H12N4OS (260.32 g/mol): C, 55.37; H, 4.65; N, 21.52;
S, 12.32. Found: C, 55.49; H, 4.65; N, 21.53; S, 12.37.
2.2.7. 4-{[(4-Hydroxyphenyl)amino]methylidene}-3-methyl-1-
phenyl-4,5-dihydro-1H-pyrazol-5-one (3g)
0.38 g (86%); yellow powder; Mp = 277–278 °C. 1H NMR
(200 MHz, DMSO-d6): 2.26 (s, 3H, CH3), 6.83 (d, 2H, J = 9.0 Hz,
ArAH), 7.11 (t, 1H, J = 7.4 Hz, ArAH), 7.35–7.43 (m, 4H, ArAH),
8.00 (dd, 2H, J = 7.4 and 1.2 Hz, ArAH), 8.45 (bs, 1H, @CHAN),
9.62 (s, 1H, OH), 11.36 (bs, 1H, NH). 13C NMR (50 MHz, DMSO-
d6): d = 12.69, 100.93, 116.29, 117.80, 119.77, 123.83, 128.96,
130.88, 139.47, 146.18, 149.01, 155.80, 165.20. IR (KBr disc,
cmꢀ1): 3411, 1665, 1650, 1596, 1522, 1485, 1306, 1267, 752. Anal.
Calcd for C17H15N3O2 (293.33 g/mol): C, 69.61; H, 5.15; N, 14.33.
Found: C, 69.94; H, 5.19; N, 14.38.
2.2.12. 4-{[(4-Methoxy-5-methyl-1H-pyrazol-3-yl)amino]methyli-
dene}-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (3l)
0.36 g (74%); yellow powder; Mp = 274–275 °C (dec). 1H NMR
(200 MHz, DMSO-d6): d = 2.27 (s, 3H, CH3), 2.45 (s, 3H, CH3), 2.56
(s, 3H, CH3), 7.14 (t, 1H, J = 7.4 Hz, ArAH), 7.41 (t, 2H, J = 7.4 Hz,
ArAH), 7.98 (dd, 2H, J = 7.4 and 1.2 Hz, ArAH), 8.43 (d, 1H,
J = 12.6 Hz, @CHAN), 12.40 (d, 1H, J = 12.6 Hz, NH), 13.11 (s, 1H,
NH, Pz). 13C NMR (50 MHz, DMSO-d6): d = 12.48, 12.66, 29.66,
103.43, 108.10, 117.83, 124.04, 129.01, 139.16, 142.35, 144.24,
149.06, 149.23, 164.78, 193.88. IR (KBr disc, cmꢀ1): 3444, 3254,
1674, 1644, 1619, 1593, 1535, 1494, 1321, 1271, 951, 584. Anal.
Calcd for C17H17N5O2 (323.35 g/mol): C, 63.15; H, 5.30; N, 21.66.
Found: C, 63.20; H, 5.31; N, 21.69.
2.2.8. 3-Methyl-1-phenyl-4-{[(thiophen-2-ylmethyl)-
amino]methylidene}-4,5-dihydro-1H-pyrazol-5-one (3h)
0.28 g (62%); light yellow crystals; Mp = 116–117 °C. 1H NMR
(200 MHz, DMSO-d6): d = 2.17 (s, 3H, CH3), 4.83 (s, 2H, CH2),
7.02–7.16 (m, 3H, 2H(Thi) and 1H(Ar)), 7.32 (t, 2H, J = 7.4 Hz,
ArAH), 7.52 (dd, 1H, J = 5.2 and 1.2 Hz, ThiAH), 7.96 (dd, 2H,
J = 7.4 and 1.2 Hz, ArAH), 8.13 (d, 1H, J = 12.0 Hz, @CHAN), 9.89
(bs, 1H, NH). 13C NMR (50 MHz, DMSO-d6): d = 12.52, 47.00,
99.50, 117.66, 123.53, 126.60, 127.03, 127.47, 128.86, 139.67,
140.42, 148.55, 153.05, 165.16. IR (KBr disc, cmꢀ1): 3446, 3283,
1662, 1621, 1593, 1553, 1499, 1308, 1286, 1254, 758, 701, 693.
Anal. Calcd for C16H15N3OS (297.38 g/mol): C, 64.62; H, 5.08; N,
14.13; S, 10.78. Found: C, 64.90; H, 5.09; N, 14.15; S, 10.83.
2.2.13. 4-{[(4-Ethoxycarbonyl-1H-pyrazol-3-yl)amino]methylidene}-
3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (3m)
0.33 g (65%); yellow crystals; Mp = 244–245 °C (dec). 1H NMR
(200 MHz, DMSO-d6): d = 1.36 (t, 3H, J = 7.2 Hz, CH3), 2.54 (s, 3H,
CH3), 4.32 (q, 2H, J = 7.2 Hz, CH2), 7.13 (t, 1H, J = 7.4 Hz, ArAH),
7.41 (t, 2H, J = 7.4 Hz, ArAH), 7.98 (dd, 2H, J = 7.4 and 1.2 Hz,
ArAH), 8.38 (d, 1H, J = 1.8 Hz, PzAH), 8.44 (d, 1H, J = 12.2 Hz,
@CHAN), 11.78 (d, 1H, J = 12.2 Hz, NH), 13.45 (s, 1H, NH, Pz). 13C
NMR (50 MHz, DMSO-d6): d = 12.58, 14.33, 60.42, 101.11, 103.42,
117.87, 124.08, 128.99, 134.10, 139.10, 142.78, 147.96, 149.16,
162.79, 165.10. IR (KBr disc, cmꢀ1): 3439, 3352, 1661, 1611,
2.2.9. 3-Methyl-1-phenyl-4-{[(pyridin-2-ylmethyl)-
amino]methylidene}-4,5-dihydro-1H-pyrazol-5-one (3i)
0.28 g (63%); white crystals; Mp = 92–93 °C (dec). 1H NMR
(200 MHz, DMSO-d6): d = 2.18 (s, 3H, CH3), 4.68 (s, 2H, CH2), 7.07
(t, 1H, J = 7.4 Hz, ArAH), 7.35 (t, 2H, J = 7.4 Hz, ArAH), 7.42 (two
d, 1H, J = 4.8 and 5.8 Hz, PyAH), 7.82 (dt, 1H, J = 5.8 and 1.6 Hz,
PyAH), 7.98 (dd, 2H, J = 7.4 and 1.2 Hz, ArAH), 8.17 (d, 1H,
J = 8.2 Hz, @CHAN), 8.54 (dd, 1H, J = 4.8 and 1.6 Hz, PyAH), 8.62
(d, 1H, J = 1.6 Hz, PyAH), 9.90 (bs, 1H, NH). 13C NMR (50 MHz,
DMSO-d6): d = 12.57, 50.09, 99.57, 117.65, 123.50, 123.95,
128.86, 133.75, 135.78, 139.73, 148.66, 149.23, 149.40, 153.68,
165.16. IR (KBr disc, cmꢀ1): 3422, 3205, 1668, 1628, 1593, 1547,
1500, 1488, 1440, 1345, 1238, 759. Anal. Calcd for C17H16N4O
(292.34 g/mol): C, 69.85; H, 5.52; N, 19.16. Found: C, 70.01; H,
5.54; N, 19.21.
1601, 1541, 1279, 1089, 751. Anal. Calcd for
C17H17N5O3
(339.35 g/mol): C, 60.17; H, 5.05; N, 20.64. Found: C, 60.28; H,
5.02; N, 20.64.
2.2.14. 4-({[5-(Furan-2-yl)-1H-pyrazol-3-yl]amino}methylidene)-3-
methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (3n)
0.35 g (70%); yellow crystals; Mp = 230–231 °C (dec). 1H NMR
(200 MHz, DMSO-d6): d = 2.27 (s, 3H, CH3), 6.65 (two d, 1H,
J = 2.0 and 1.6 Hz, FurAH), 6.79 (d, 1H, J = 2.0 Hz, FurAH), 6.87 (d,
1H, J = 3.2 Hz, PzAH), 7.13 (t, 1H, J = 7.4 Hz, ArAH), 7.41 (t, 2H,
J = 7.4 Hz, ArAH), 7.82 (d, 1H, J = 1.6 Hz, FurAH), 7.99 (dd, 2H,
J = 7.4 and 1.2 Hz, ArAH), 8.49 (s, 1H, ACH = N), 11.18 (bs, 1H,
OH), 13.29 (d, 1H, J = 2.0 Hz, NH, Pz). 13C NMR (50 MHz, DMSO-
d6): d = 12.64, 90.91, 101.83, 107.69, 112.12, 117.90, 124.03,
129.00, 135.68, 139.26, 143.67, 144.34, 145.70, 149.13, 149.23,
165.13. IR (KBr disc, cmꢀ1): 3446, 3231, 1671, 1614, 1596, 1542,
1498, 1400, 1320, 753. Anal. Calcd for C18H15N5O2 (333.35 g/
mol): C, 64.86; H, 4.54; N, 21.01. Found: C, 65.00; H, 4.86; N, 21.07.
2.2.10. 4-{[(Furan-2-ylmethyl)amino]methylidene}-3-methyl-1-
phenyl-4,5-dihydro-1H-pyrazol-5-one (3j)
0.16 g (38%); yellow-orange powder; Mp = 110–111 °C. 1H NMR
(200 MHz, DMSO-d6): d = 2.17 (s, 3H, CH3), 4.67 (s, 2H, CH2), 6.42–
6.48 (m, 2H, FurAH), 7.08 (t, 1H, J = 7.4 Hz, ArAH), 7.36 (t, 2H,
J = 7.4 Hz, ArAH), 7.68 (dd, 1H, J = 2.6 and 1.0 Hz, FurAH), 7.96
(dd, 2H, J = 7.4 and 1.2 Hz, ArAH), 8.10 (d, 1H, J = 8.8 Hz, @CHAN),
9.75 (bs, 1H, NH). 13C NMR (50 MHz, DMSO-d6): d = 12.50, 45.24,
99.56, 108.65, 110.97, 117.67, 123.55, 128.86, 139.65, 143.53,
148.51, 150.72, 153.44, 165.20. IR (KBr disc, cmꢀ1): 3436, 3290,
1666, 1625, 1593, 1502, 1487, 1310, 1299, 761. Anal. Calcd for
2.2.15. 3-Methyl-4-{[(5-methyl-1H-pyrazol-3-yl)amino]methyli-
dene}-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (3o)
0.26 g (62%); yellow powder; Mp = 213–214 °C (dec). 1H NMR
(200 MHz, DMSO-d6): d = 2.24 (s, 3H, CH3), 2.25 (s, 3H, CH3), 6.25
(d, 1H, J = 1.4 Hz, PzAH), 7.12 (t, 1H, J = 7.4 Hz, ArAH), 7.40 (t,
2H, J = 7.4 Hz, ArAH), 7.98 (dd, 2H, J = 7.4 and 1.2 Hz, ArAH), 8.39
(s, 1H, ACH@N), 11.17 (bs, 1H, OH), 12.45 (s, 1H, NH, Pz). 13C
NMR (50 MHz, DMSO-d6): d = 10.82, 12.62, 93.31, 101.35, 117.89,
123.97, 128.98, 139.32, 140.88, 145.64, 148.44, 149.02, 165.18. IR
(KBr disc, cmꢀ1): 3437, 3245, 1669, 1620, 1595, 1548, 1499,
1320, 1302, 755. Anal. Calcd for C15H15N5O (281.32 g/mol): C,
64.04; H, 5.37; N, 24.89. Found: C, 64.44; H, 5.40; N, 24.94.
C16H15N3O2 (281.31 g/mol): C, 68.31; H, 5.37; N, 14.94. Found: C,
68.67; H, 5.38; N, 14.97.
2.2.11. 3-Methyl-1-phenyl-4-thioureidomethylidene-4,5-dihydro-1H-
pyrazol-5-one (3k)
0.30 g (77%); yellow powder; Mp = 227–228 °C (dec). 1H NMR
(200 MHz, DMSO-d6): d = 2.25 (s, 3H, CH3), 7.16 (t, 1H, J = 7.4 Hz,
ArAH), 7.42 (t, 2H, J = 7.4 Hz, ArAH), 7.92 (dd, 2H, J = 7.4 and
1.2 Hz, ArAH), 8.63 (bs, 1H, @CHAN), 9.38 (s, 1H, C(@S)NH), 9.55