10
L. Li et al. / Bioorg. Med. Chem. xxx (2016) xxx–xxx
1557, 1495, 1276. 1H NMR (400 MHz, DMSO) d 9.64 (s, 1H), 7.41 (d,
J = 7.3 Hz, 2H), 7.29 (dt, J = 12.7, 7.0 Hz, 6H), 7.10–6.97 (m, 4H),
6.72 (d, J = 8.4 Hz, 2H), 5.72–5.56 (m, 1H), 5.05 (d, J = 15.2 Hz,
1H), 4.67 (d, J = 9.9 Hz, 1H), 3.90–3.73 (m, 1H), 3.53 (d,
J = 15.2 Hz, 1H), 3.17 (dd, J = 17.0, 13.3 Hz, 1H), 2.81–2.69 (m,
1H). 13C NMR (100 MHz, DMSO) d 168.35, 158.50, 138.42, 136.95,
129.93, 129.36, 129.11, 128.85, 128.63, 128.31, 128.00, 127.50,
125.99, 116.06, 93.31, 64.06, 46.34, 43.00, 38.00. ESI-MS [MÀH]À
(m/z):401.1. C24H22N2O4 [402.16].
4.1.4.11. ( )-1-(3,4-Dimethoxybenzyl)-6-(4-hydroxyphenyl)-5-
nitro-4-phenylpiperidin-2-one (7f). White powder, yield:
43.5%, mp 275.3–277.6 °C. Purity: 94.4%, tR = 5.41 min. IR (KBr)
r
/
cmÀ1 3467, 2961, 1610, 1560, 1450, 1271. 1H NMR (400 MHz,
DMSO) d 9.70 (s, 1H), 7.44 (d, J = 7.1 Hz, 2H), 7.36 (t, J = 7.3 Hz,
2H), 7.30 (t, J = 7.2 Hz, 1H), 7.11 (d, J = 8.5 Hz, 2H), 6.93 (d,
J = 8.3 Hz, 1H), 6.79 (d, J = 8.5 Hz, 2H), 6.65 (dd, J = 8.2, 1.7 Hz,
1H), 6.55 (d, J = 1.8 Hz, 1H), 5.63 (dd, J = 11.6, 9.9 Hz, 1H), 5.08 (d,
J = 14.8 Hz, 1H), 4.69 (d, J = 9.8 Hz, 1H), 3.90–3.61 (m, 7H), 3.48
(d, J = 14.8 Hz, 1H), 3.20 (dd, J = 16.9, 13.2 Hz, 1H), 2.77 (dd,
J = 17.0, 4.7 Hz, 1H). 13C NMR (100 MHz, DMSO) d 168.30, 158.49,
149.00, 148.42, 138.38, 129.99, 129.29, 129.10, 128.31, 128.01,
126.18, 120.53, 116.03, 112.33, 112.23, 93.48, 63.84, 55.96, 55.83,
45.98, 43.04, 37.96. ESI-MS [MÀH]À (m/z):461.1. C26H26N2O6
[462.18].
4.1.4.7. ( )-1-(4-Fluorobenzyl)-6-(4-hydroxyphenyl)-5-nitro-4-
phenylpiperidin-2-one (7b).
269.1–271.0 °C. Purity: 96.7%, tR = 10.77 min. IR (KBr)
White foam, yield: 26.7%, mp
r
/cmÀ1
3448, 2923, 1613, 1558, 1459, 1245. 1H NMR (400 MHz, DMSO) d
9.70 (s, 1H), 7.45 (d, J = 7.3 Hz, 2H), 7.37 (t, J = 7.4 Hz, 2H), 7.30
(t, J = 7.2 Hz, 1H), 7.18–7.07 (m, 6H), 6.75 (d, J = 8.5 Hz, 2H),
5.73–5.63 (m, 1H), 4.95 (d, J = 15.1 Hz, 1H), 4.74 (d, J = 9.8 Hz,
1H), 3.86 (td, J = 12.5, 4.7 Hz, 1H), 3.70 (d, J = 15.2 Hz, 1H), 3.21
(dd, J = 17.0, 13.2 Hz, 1H), 2.77 (dd, J = 17.0, 4.8 Hz, 1H). 13C NMR
4.1.4.12. ( )-1-Benzyl-4-(2-chlorophenyl)-6-(4-hydroxyphenyl)-
5-nitropiperidin-2-one (7g).
236.1–237.5 °C. Purity: 96.9%, tR = 10.88 min. IR (KBr)
White powder, yield: 44.2%, mp
r
/cmÀ1
(100 MHz, DMSO)
d
168.44, 160.46, 158.51, 138.42, 133.33,
3468, 1618, 1561, 1453, 1271. 1H NMR (400 MHz, DMSO) d 9.65
(s, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.38 (t,
J = 7.5 Hz, 1H), 7.32–7.21 (m, 4H), 7.08 (d, J = 8.4 Hz, 2H), 7.00 (d,
J = 7.1 Hz, 2H), 6.70 (d, J = 8.4 Hz, 2H), 5.87–5.76 (m, 1H), 4.90 (d,
J = 15.2 Hz, 1H), 4.75 (d, J = 9.8 Hz, 1H), 4.32 (td, J = 12.4, 4.9 Hz,
1H), 3.70 (d, J = 15.2 Hz, 1H), 3.06 (dd, J = 16.8, 13.2 Hz, 1H), 2.76
(dd, J = 17.1, 4.9 Hz, 1H). 13C NMR (100 MHz, DMSO) d 167.92,
158.55, 137.20, 135.53, 133.17, 130.23, 130.13, 129.94, 128.78,
128.31, 127.99, 127.48, 125.66, 115.99, 91.62, 64.30, 46.82, 37.30.
ESI-MS [MÀH]À (m/z):435.1. C24H21ClN2O4 [436.12].
133.30, 130.09, 130.02, 129.13, 128.32, 128.00, 125.87, 116.00,
115.61, 115.40, 93.19, 64.18, 45.92, 42.97, 38.00. ESI-MS [MÀH]À
(m/z):419.1. C24H21FN2O4 [420.15].
4.1.4.8. ( )-6-(4-Hydroxyphenyl)-1-(4-methylbenzyl)-5-nitro-4-
phenylpiperidin-2-one (7c).
275.6–278.1 °C. Purity: 95.4%, tR = 8.95 min. IR (KBr)
White powder, yield: 37.2%, mp
r
/cmÀ1 3449,
3125, 1617, 1561, 1456, 1273. 1H NMR (400 MHz, DMSO) d 9.70 (s,
1H), 7.42 (d, J = 7.3 Hz, 2H), 7.33 (t, J = 7.4 Hz, 2H), 7.27 (d,
J = 7.2 Hz, 1H), 7.13 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.4 Hz, 2H),
6.94 (d, J = 7.9 Hz, 2H), 6.76 (d, J = 8.5 Hz, 2H), 5.63 (dd, J = 11.5,
10.1 Hz, 1H), 5.12 (d, J = 15.0 Hz, 1H), 4.63 (d, J = 9.9 Hz, 1H), 3.77
(td, J = 12.6, 4.6 Hz, 1H), 3.40 (d, J = 15.1 Hz, 1H), 3.18 (dd,
J = 16.9, 13.2 Hz, 1H), 2.75 (dd, J = 17.0, 4.7 Hz, 1H), 2.30 (s, 3H).
13C NMR (100 MHz, DMSO) d 168.27, 158.50, 138.38, 136.68,
133.77, 129.88, 129.50, 129.11, 128.32, 128.09, 128.02, 126.05,
116.10, 93.37, 63.82, 45.83, 42.98, 37.98, 21.17. ESI-MS [MÀH]À
(m/z):415.1. C25H24N2O4 [416.17].
4.1.4.13.
methylbenzyl)-5-nitropiperidin-2-one (7h).
yield: 48.6%, mp 265.6–266.3 °C. Purity: 99.3%, tR = 12.97 min. IR
(KBr)
/cmÀ1 3224, 1619, 1558, 1460, 1271. 1H NMR (400 MHz,
( )-4-(2-Chlorophenyl)-6-(4-hydroxyphenyl)-1-(4-
White powder,
r
DMSO) d 9.67 (s, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 7.9 Hz,
1H), 7.37 (t, J = 7.5 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.09 (t,
J = 7.7 Hz, 4H), 6.90 (d, J = 7.8 Hz, 2H), 6.74 (d, J = 8.4 Hz, 2H),
5.87–5.73 (m, 1H), 4.98 (d, J = 15.0 Hz, 1H), 4.68 (d, J = 9.7 Hz,
1H), 4.28 (td, J = 12.4, 4.8 Hz, 1H), 3.53 (d, J = 15.0 Hz, 1H), 3.06
(dd, J = 16.8, 13.3 Hz, 1H), 2.75 (dd, J = 17.1, 4.9 Hz, 1H), 2.27 (s,
3H). 13C NMR (100 MHz, DMSO) d 167.82, 158.57, 136.69, 135.47,
133.98, 133.16, 130.22, 130.04, 129.93, 129.45, 128.30, 128.09,
125.76, 116.07, 91.73, 64.06, 46.26, 37.29, 21.15. ESI-MS [MÀH]À
(m/z):449.1. C25H23ClN2O4 [450.13].
4.1.4.9. ( )-6-(4-Hydroxyphenyl)-1-(4-methoxybenzyl)-5-nitro-
4-phenylpiperidin-2-one (7d).
mp 277.9–279.1 °C. Purity: 96.1%, tR = 8.5 min. IR (KBr)
White powder, yield: 38.6%,
r
/cmÀ1
3450, 3125, 1614, 1560, 1439, 1247. 1H NMR (400 MHz, DMSO) d
9.69 (s, 1H), 7.41 (d, J = 8.1 Hz, 2H), 7.32 (t, J = 7.4 Hz, 2H), 7.27
(d, J = 7.2 Hz, 1H), 7.07 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.5 Hz, 2H),
6.87 (d, J = 8.6 Hz, 2H), 6.76 (d, J = 8.5 Hz, 2H), 5.61 (t, J = 10.8 Hz,
1H), 5.08 (d, J = 14.9 Hz, 1H), 4.64 (d, J = 9.8 Hz, 1H), 3.79–3.71
(m, 4H), 3.41 (d, J = 14.9 Hz, 1H), 3.17 (dd, J = 16.8, 13.3 Hz, 1H),
2.73 (dd, J = 17.0, 4.7 Hz, 1H). 13C NMR (100 MHz, DMSO) d
168.25, 158.82, 158.49, 138.38, 129.89, 129.52, 129.11, 128.72,
128.31, 128.01, 126.11, 116.09, 114.29, 93.42, 63.77, 55.47, 45.53,
42.99, 37.99. ESI-MS [MÀH]À (m/z):431.1. C25H24N2O5 [432.17].
4.1.4.14.
methoxybenzyl)-5-nitropiperidin-2-one (7i).
der, yield: 42.4%, mp 268.0–269.7 °C. Purity: 98.6%, tR = 8.57 min.
IR (KBr)
/cmÀ1 3436, 3199, 1618, 1557, 1462, 1272. 1H NMR
( )-4-(2-Chlorophenyl)-6-(4-hydroxyphenyl)-1-(4-
White pow-
r
(400 MHz, DMSO) d 9.67 (s, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.42 (d,
J = 8.0 Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.28 (t, J = 7.5 Hz, 1H), 7.08
(d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.5 Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H),
6.74 (d, J = 8.4 Hz, 2H), 5.85–5.73 (m, 1H), 4.94 (d, J = 14.9 Hz,
1H), 4.69 (d, J = 9.7 Hz, 1H), 4.26 (td, J = 12.4, 4.8 Hz, 1H), 3.74 (d,
J = 9.2 Hz, 3H), 3.53 (d, J = 14.8 Hz, 1H), 3.04 (dd, J = 16.8, 13.3 Hz,
1H), 2.74 (dd, J = 17.1, 4.9 Hz, 1H). 13C NMR (100 MHz, DMSO)
d 167.79, 158.82, 158.55, 135.47, 133.16, 130.22, 130.05, 129.93,
129.52, 128.94, 128.30, 125.81, 116.05, 114.26, 91.76,
64.00, 55.47, 45.95, 38.96, 37.31. ESI-MS [MÀH]À (m/z):465.1.
C25H23ClN2O5 [466.13].
4.1.4.10.
nitro-4-phenylpiperidin-2-one (7e).
41.4%, mp 262.2–263.2 °C. Purity: 97.7%, tR = 9.22 min. IR (KBr)
( )-6-(4-Hydroxyphenyl)-1-(3-methoxybenzyl)-5-
White powder, yield:
r/
cmÀ1 3467, 1618, 1560, 1452, 1278. 1H NMR (400 MHz,) d 9.67
(s), 7.41 (d, J = 7.2 Hz), 7.32 (t, J = 7.4 Hz), 7.28–7.19 (m), 7.06 (d,
J = 8.5 Hz), 6.82 (dd, J = 8.1, 2.3 Hz), 6.72 (d, J = 8.5 Hz), 6.63 (d,
J = 7.6 Hz), 6.52 (s), 5.63 (dd, J = 11.6, 10.0 Hz), 5.00 (d,
J = 15.2 Hz), 4.68 (d, J = 9.9 Hz), 3.79 (td, J = 12.6, 4.7 Hz), 3.71 (s),
3.52 (d, J = 15.2 Hz), 3.16 (dd, J = 17.0, 13.2 Hz), 2.74 (dd, J = 17.1,
4.8 Hz). 13C NMR (100 MHz, DMSO) d 168.35, 159.69, 158.51,
138.61, 130.00, 129.11, 128.32, 128.03, 125.98, 120.12, 116.01,
113.75, 112.93, 93.27, 64.10, 55.37, 43.03. ESI-MS [MÀH]À (m/
z):431.1. C25H24N2O5 [432.17].
4.1.4.15.
methoxybenzyl)-5-nitropiperidin-2-one (7j).
der, yield: 38.8%, mp 228.8–230.4 °C. Purity: 93.9%, tR = 9.89 min.
IR (KBr)
/cmÀ1 3468, 1613, 1560, 1487, 1276. 1H NMR
(400 MHz, DMSO) d 9.65 (s, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.43 (d,
( )-4-(2-Chlorophenyl)-6-(4-hydroxyphenyl)-1-(3-
White pow-
r