J. Dennis Bilavendran, et al.
BioorganicChemistryxxx(xxxx)xxxx
NMR (400 MHz, CDCl3) δ ppm: 7.77 (d, J = 8.0 Hz, 2H), 7.52 (s, 1H),
7.17 (d, J = 8.0 Hz, 2H), 7.14 (s, 1H), 3.31 (d, J = 4.0 Hz, 4H),
2.64–2.60 (m, 4H), 2.22 (s, 3H), 1.27 (t, J = 8.0 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ ppm: 186.4, 146.7, 146.6, 142.2, 142.0, 141.9,
141.8, 141.7, 135.9, 135.7, 135.6, 126.9, 126.8, 64.0, 56.7, 44.9, 24.2,
2.83–2.69 (m, 2H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm:
164.5, 164.4, 162.1, 162.0, 156.0, 147.2, 147.1, 146.6, 145.7, 145.6,
137.9, 130.4, 130.3, 129.9, 129.8, 129.3, 129.2, 126.2, 126.0, 122.4,
122.3, 122.2, 122.1, 116.9, 114.5, 114.3, 60.1, 57.8, 55.1, 33.7, 31.1;
Elemental Analysis, Calculated: C, 67.49; H, 5.41; N, 10.73; S, 16.38;
Obtained: C, 67.51; H, 5.43; N, 10.71; S, 16.36; HRMS for C22H21N3S2
Calculated [M+] m/z 391.5510, Found 391.5510.
24.1, 16.2, 16.1; HRMS for C20H23NOS2 Calculated [M+
357.5300, Found 357.5300.
] m/z
(3Z,5E)-3,5-bis((4-bromo-5-methylthiophen-2-yl)methylene)-1-
methylpiperidin-4-one (3i): Deep-Yellow solid; Melting point:
96–98 °C: IR (KBr): 2998, 2864, 1847, 1718, 1548, 1356, 1214, 864,
752, 644 cm−1: 1H NMR (400 MHz, CDCl3) δ ppm: 7.74 (s, 2H), 7.56 (s,
1H), 7.08 (s, 1H), 3.31 (d, J = 8.0 Hz, 4H), 2.26 (s, 6H), 2.12 (s, 3H);
13C NMR (100 MHz, CDCl3) δ ppm: 186.2, 146.2, 141.9, 141.8, 138.4,
138.2, 138.0, 137.8, 137.6, 137.0, 123.2, 123.1, 110.2, 108.2, 108.1,
(E)-5-methyl-2-phenyl-3-(thiophen-3-yl)-7-(thiophen-3-yl-
methylene)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine
(5b): Light-Orange solid; Melting point: 178–180 °C: IR (KBr): 3108,
3024, 2934, 2858, 2306, 1742, 1590, 1468, 1406, 1380, 1268, 1234,
1112, 898, 760, 698, 678, 662 cm−1
:
1H NMR (400 MHz, CDCl3) δ
ppm: 8.07–7.81 (m, 6H), 7.50–7.37 (m, 5H), 7.06 (s, 1H), 4.54 (d,
J = 8.0 Hz, 1H), 3.59–3.56 (m, 2H), 2.87–2.65, (m, 3H), 2.30–2.28 (m,
3H); 13C NMR (100 MHz, CDCl3) δ ppm: 156.1, 147.1, 144.1, 142.7,
138.0, 137.9, 137.8, 128.8, 128.7, 128.4, 127.9, 127.8, 127.3, 126.9,
126.0, 125.6, 123.6, 123.6, 115.9, 33.6, 30.9; Elemental Analysis,
calculated: C, 67.49; H, 5.41; N, 10.73; S, 16.38; Obtained: C, 67.48; H,
5.43; N, 10.72; S, 16.40; HRMS for C22H21N3S2 Calculated [M+] m/z
391.5510, Found 391.5510.
62.1, 55.9, 45.9, 15.2, 15.1; HRMS for C18H17Br2NOS2 Calculated [M+
m/z 487.2680, Found 487.2679.
]
(3Z,5E)-1-methyl-3,5-bis((5-nitrothiophen-2-yl)methylene)pi-
peridin-4-one (3j): Deep-Orange solid; Melting point: 112–114 °C: IR
(KBr): 3064, 2994, 2224, 1846, 1756, 1504, 1421, 1202, 864, 752,
640 cm−1: 1H NMR (400 MHz, CDCl3) δ ppm: 8.61 (d, J = 8.0 Hz, 2H),
7.81 (d, J = 8.0 Hz, 2H), 7.56 (s, 1H), 7.12 (s, 1H), 3.31 (d, J = 4.0 Hz,
4H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm: 184.5, 146.1,
1417, 140.4, 137.6, 137.4, 137.0, 130.6, 130.5, 129.2, 129.0, 128.3,
128.1, 64.0, 56.4, 42.4; HRMS for C16H13N3O5S2 Calculated [M+] m/z
391.4160, Found 391.4163.
(E)-3-(5-bromothiophen-2-yl)-7-((5-bromothiophen-2-yl)me-
thylene)-5-methyl-2-phenyl-3, 3a,4,5,6,7-hexahydro-2H-pyrazolo
[4,3-c]pyridine (5c): Pale yellow powder; Melting point: 190–192 °C:
IR (KBr): 3024, 3012, 2924, 2858, 2345, 1818, 1748, 1564, 1432,
1378, 1268, 1234, 1112, 896, 760, 698, 676, 662, 640 cm−1
:
1H NMR
(3Z,5E)-1-methyl-3-((3-methylthiophen-2-yl)methylene)-5-((4-
methylthiophen-2-yl)methyle ne)piperidin-4-one (3k): Orange
solid; Melting point: 108–110 °C: IR (KBr): 3011, 2346, 1802, 1712,
(400 MHz, CDCl3) δ ppm: 7.74–7.32 (m, 2H), 7.27–7.15 (m, 6H), 6.87
(d, J = 4.0 Hz, 1H), 3.73 (d, J = 4.0 Hz, 2H), 3.59–3.40 (m, 2H),
2.80–2.70 (m, 2H), 2.31–2.01 (m, 4H); 13C NMR (100 MHz, CDCl3) δ
ppm: 160.5, 143.4, 142.5, 141.1, 139.5, 138.1, 137.2, 132.9, 130.9,
129.9, 129.8, 128.4, 127.6, 127.5, 127.1, 126.9, 126.3, 124.5, 122.5,
119.4, 116.6, 110.2, 96.4, 60.2, 59.3, 52.7, 43.8, 43.6; Elemental
Analysis, calculated: C, 48.10; H, 3.49; Br, 29.09; N, 7.65; S, 11.67;
Obtained: C, 48.12; H, 3.47; Br, 29.11; N, 7.63; S, 11.67; HRMS for
1564, 1348, 1202, 752, 684, 640 cm−1
:
1H NMR (400 MHz, CDCl3) δ
ppm: 8.02 (d, J = 4.0 Hz, 1H), 7.56 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H),
7.26 (d, J = 8.0 Hz, 1H), 7.08 (s, 1H), 6.67 (d, J = 8.0 Hz, 1H), 3.17 (d,
J = 4.0 Hz, 4H), 2.38 (s, 3H), 2.26 (d, J = 8.0 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ ppm: 186.2, 152.4, 146.8, 146.7, 141.9, 141.8,
138.3, 137.9, 135.1, 131.9, 130.3, 127.7, 125.4, 62.1, 56.1, 45.0, 15.6,
14.5; HRMS for C18H19NOS2 Calculated [M+] m/z 329.4760, Found
329.4765.
C
22H19Br2N3S2 Calculated [M+] m/z 549.3430, Found 549.3432.
(E)-3-(5-chlorothiophen-2-yl)-7-((5-chlorothiophen-2-yl)me-
thylene)-5-methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo
[4,3-c]pyridine (5d): Pale yellow powder; Melting point: 194–196 °C:
IR (KBr): 3024, 2996, 2884, 2320, 1738, 1588, 1470, 1436, 1348,
(3Z,5E)-3,5-bis((4-fluoro-5-methylthiophen-2-yl)methylene)-1-
methylpiperidin-4-one (3l): Brownish solid; Melting point:
120–122 °C: IR (KBr): 3120, 2998, 2214, 1864, 1702, 1564, 1312,
1234, 1208, 1120, 888, 768, 670, 662, 656, 642 cm−1
:
1H NMR
1212, 864, 752, 642 cm−1
:
1H NMR (400 MHz, CDCl3) δ ppm: 7.60 (s,
(400 MHz, CDCl3) δ ppm: 7.15–6.96 (m, 5H), 6.47–6.31 (m, 2H),
6.24–6.17 (m, 2H), 3.95 (d, J = 8.0 Hz, 1H), 3.53–3.42 (m, 2H),
2.86–2.70 (m, 2H), 2.41–2.11 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
ppm: 156.4, 147.3, 144.4, 142.9, 138.3, 138.2, 138.0, 126.2, 125.9,
123.8, 123.8, 116.1, 113.2, 59.8, 58.4, 55.4, 33.8, 31.1; Elemental
Analysis, calculated: C, 57.39; H, 4.16; Cl, 15.40; N, 9.13; S, 13.93;
Obtained: C, 57.37; H, 4.18; Cl, 15.42; N, 9.11; S, 13.95; HRMS for
1H), 7.27 (d, J = 8.0 Hz, 2H), 7.12 (s, 1H), 3.21 (d, J = 4.0 Hz, 4H),
2.34 (s, 6H), 2.22 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm: 184.1,
146.8, 141.9, 140.8, 137.8, 137.1, 137.0, 130.6, 130.5, 129.2, 129.1,
128.3, 128.0, 64.1, 56.8, 42.9; HRMS for C18H17F2NOS2 Calculated
[M+] m/z 365.4568, Found 365.4571.
2.2. Synthesis of (E)-5-methyl-2-phenyl-3-(thiophen-2-yl)-7-(thiophen-2-
ylmethylene)-3,3a,4,5,6, 7-hexahydro-2H-pyrazolo[4,3-c]pyridine (5a-l)
C
22H19Cl2N3S2 Calculated [M+] m/z 460.4350, Found 460.4350.
(E)-3-(5-fluorothiophen-2-yl)-7-((5-fluorothiophen-2-yl)methy-
lene)-5-methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-
c]pyridine (5e): Yellowish solid; Melting point: 186–188 °C: IR (KBr):
3088, 3021, 2918, 2866, 2331, 1734, 1586, 1464, 1432, 1387, 1265,
A mixture of intermediate 3 (0.0025 mol) and phenylhydrazine (4)
(0.0025 mol) was refluxed in 25 ml of isopropanol. The completion of
reaction was monitored by TLC using ethyl acetate and hexane mixture
(1:9) as eluent. Once the reaction completed, the reaction mixture was
kept aside to reach room temperature and poured into the crushed ice
with continuous stirring and the solid obtained was filtered and washed
with water. The crude product was dried and purified over column
chromatography using ethyl acetate and hexane (1:9) as an eluen. The
isolated pure and final product from column chromatography was re-
crystallized using ethanol and THF in 1:1 ratio.
1213, 1118, 894, 754, 696, 674, 664, 641 cm−1
:
1H NMR (400 MHz,
CDCl3) δ ppm: 7.24 (d, J = 2.8 Hz, 2H), 7.14–7.06 (m, 5H), 6.96–6.88
(m, 1H), 6.69–6.63 (m, 1H), 6.57–6.37 (m, 1H), 3.74 (d, J = 4.0 Hz,
1H), 2.85–2.75 (m, 2H), 2.17–2.10 (m, 2H), 1.56–1.45 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ ppm: 164.6, 164.5, 162.1, 162.0, 156.0,
147.1, 147.0, 146.7, 145.8, 145.7, 137.9, 130.5, 130.4, 130.0, 129.9,
129.3, 122.2, 122.1, 117.1, 114.5, 113.8, 113.2, 97.8, 60.18, 57.8,
33.7, 31.2; Elemental Analysis calculated: C, 61.81; H, 4.48; F, 8.89; N,
9.83; S, 15.00; Obtained: C, 61.83; H, 4.46; F, 8.89; N, 9.81; S, 15.02; S,
9.13; HRMS for C22H19F2N3S2 Calculated [M+] m/z 427.5318, Found
427.5317.
(E)-5-methyl-2-phenyl-3-(thiophen-2-yl)-7-(thiophen-2-yl-
methylene)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine
(5a): Pale yellow powder; Melting point: 168–170 °C: IR (KBr): 3096,
3022, 2916, 2870, 2334, 1732, 1584, 1462, 1432, 1386, 1260, 1212,
1116, 897, 756, 694, 672, 666, 642 cm−1: 1H NMR (400 MHz, CDCl3) δ
ppm: 8.13 (s, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.91–7.90 (m, 2H),
7.48–7.16 (m, 8H), 3.96 (d, J = 3.6 Hz, 2H), 3.72–3.64 (m, 2H),
(E)-5-methyl-3-(5-methylthiophen-2-yl)-7-((5-methylthiophen-
2-yl)methylene)-2-phenyl-3,
3a,4,5,6,7-hexahydro-2H-pyrazolo
[4,3-c]pyridine (5f): Light-brown powder; Melting point: 182–184 °C:
IR (KBr): 3084, 3016, 2977, 2836, 2334, 1750, 8 1464, 1434, 1386,
3