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N. Samaan et al. / European Journal of Medicinal Chemistry 75 (2014) 123e131
4.3.5. (3E,5E)-1-Methyl-3,5-bis((1-methyl-1H-pyrazol-5-yl)
methylene)piperidin-4-one (25)
4H), 3.82 (s, 6H), 7.02 (s, 2H), 7.32 (s, 2H), 7.55 (s, 2H). 13C NMR
(75 MHz, CDCl3)
190.1.
d: 21.5, 28.5, 33.3, 118.6, 123.0, 130.3, 138.7, 144.3,
This compound was prepared by method A in 92% yield as a
yellow crystal: mp. 155e157 ꢀC. IR (neat) nmax: 2944, 1672, 1612,
1583, 1453, 1267, 1187, 925, 608 cmꢁ1. 1H NMR (300 MHz, CD3OD)
d:
4.3.12. (2E,6E)-2,6-Bis((1-isopropyl-1H-imidazole-2-yl)methylene)
cyclohexanone (32)
This compound was prepared by method A in 74% yield as a
yelloweorange solid: mp. 158.5e160 ꢀC. IR (neat) nmax: 3104, 2977,
2933, 1660, 1608, 1567, 1463, 1248, 1157 cmꢁ1. 1H NMR (300 MHz,
2.56 (s, 3H), 3.77 (br.s, 4H), 4.00 (s, 6H), 6.56 (d, J ¼ 2.1 Hz, 2H), 7.57
(d, J ¼ 2.1 Hz, 2H), 7.69 (s, 1H). 13C NMR (75 MHz, CD3OD)
d: 35.7,
44.5, 56.0, 108.6, 120.7, 133.3, 136.8, 138.3, 185.3. HR-MS (ESI) m/z:
calcd for C16H20N5O [M þ H]: 298.1668; found 298.1662.
CDCl3)
J ¼ 5.5 Hz, 4H), 4.62 (sep, J ¼ 6.6 Hz, 2H), 7.03 (s, 2H), 7.20 (s, 2H),
7.54 (s, 2H). 13C NMR (75 MHz, CDCl3)
: 21.7, 23.7, 28.6, 47.5, 117.3,
119.3, 130.6, 138.2, 143.0, 190.2. HR-MS (ESI) m/z: calcd for
20H27N4O [M þ H]: 339.2185; found 339.2193.
d: 1.52 (d, J ¼ 6.6 Hz, 6H), 1.78 (quin, J ¼ 6.0 Hz, 2H), 3.28 (t,
4.3.6. (3E,5E)-1-Methyl-3,5-bis(thiazole-2-yl methylene)piperidin-
4-one (26)
d
This compound was prepared by method A in 71% yield as a
yellow solid: mp. 110e111 ꢀC. IR (neat) nmax: 3078, 2939, 1670, 1608,
C
1582, 1481, 1271, 1180 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d: 2.61 (s,
3H), 4.16 (s, 4H), 7.54 (d, J ¼ 3.0 Hz, 2H), 7.76 (s, 2H), 8.03 (d,
4.3.13. (2E,6E)-2,6-Bis((1-(sec-butyl)-1H-imidazol-2-yl)methylene)
cyclohexanone (33)
J ¼ 3.0 Hz, 2H). 13C NMR (75 MHz, CDCl3)
d: 45.9, 57.3, 122.4, 124.9,
135.7, 145.3, 163.1, 186.7. HR-MS (ESI) m/z: calcd for C14H14N3OS2
[M þ H]: 304.0578; found 304.0566.
This compound was prepared by method A in 72% yield as a
yellow-orange solid. 1H NMR (300 MHz, CDCl3)
d
: 0.84 (t, J ¼ 7.3 Hz,
6H), 1.45 (d, J ¼ 6.6 Hz, 6H), 1.74e1.88 (m, 6H), 3.35 (t, J ¼ 5.1 Hz,
4H), 4.43 (sex, J ¼ 6.8 Hz, 2H), 7.06 (s, 2H), 7.31 (s, 2H), 7.61 (s, 2H).
4.3.7. (3E,5E)-1-Methyl-3,5-bis(thiazol-4-ylmethylene)piperidin-4-
one (27)
13C NMR (75 MHz, CDCl3)
d: 10.6, 21.8, 28.7, 30.9, 53.4, 117.6, 119.5,
This compound was prepared by method A in 65% yield as a
130.7, 138.3, 143.6, 190.3. HR-MS (ESI) m/z: calcd for C22H31N4O
[M þ H]: 367.2498; found 367.2494.
yellow crystal: mp. 131e132 ꢀC. IR (neat) nmax: 3101, 2940, 1671,
1616, 1581, 1471, 1263, 1180 cmꢁ1. 1H NMR (300 MHz, DMSO-d6)
d
:
2.43 (s, 3H), 4.01 (s, 4H), 7.58 (s, 2H), 8.24 (s, 2H), 9.27 (s, 2H). 13
NMR (75 MHz, DMSO-d6)
C
4.3.14. (2E,6E)-2,6-Bis((1-isobutyl-1H-imidazol-2-yl)methylene)
cyclohexanone (34)
d: 46.1, 57.4, 126.1, 126.4, 133.7, 152.6,
155.6, 187.8. HR-MS (ESI) m/z: calcd for C14H14N3OS2 [M þ H]:
This compound was prepared by method A in 72% yield as a
yellow-orange solid. 75% yield. IR (neat) nmax: 3103, 2960, 1663,
304.0578; found 304.0577.
1605, 1570, 1281, 1168, 1131 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d: 0.92
4.3.8. (3E,5E)-1-Methyl-3,5-bis((2-methyloxazol-4-yl)methylene)
piperidin-4-one (28)
(d, J ¼ 6.6 Hz, 12H), 1.85 (quin, J ¼ 6.3 Hz, 2H), 2.06 (m, J ¼ 6.7 Hz,
2H), 3.35 (t, J ¼ 5 Hz, 4H), 3.87 (d, J ¼ 7.4 Hz, 4H), 6.97 (s, 2H), 7.26 (s,
This compound was prepared by method A in 6% yield as a
2H), 7.54 (s, 2H). 13C NMR (75 MHz, CDCl3)
d: 19.9, 21.6, 28.5, 30.4,
yellow crystal: mp. 138e139.5 ꢀC. 1H NMR (300 MHz, CDCl3)
d
: 2.51
(s, 6H), 2.63 (s, 3H), 4.14 (s, 4H), 7.51 (s, 2H), 7.77 (s, 2H). 13C NMR
(75 MHz, CDCl3) : 14.0, 44.9, 56.2, 124.3, 131.6, 137.6, 141.4, 162.1,
53.8, 119.4, 122.3, 130.1, 138.1, 143.9, 190.1. HR-MS (ESI) m/z: calcd
for C22H31N4O [M þ H]: 367.2498; found 367.2488.
d
185.8. HR-MS (ESI, M þ H) m/z: calcd for C16H18N3O3 [M þ H]:
4.3.15. (2E,6E)-2,6-Bis((1-methyl-1H-pyrazol-4-yl)methylene)
cyclohexanone (35)
300.1348; found 300.1351.
This compound was prepared by method A in 83% as a yellow
4.3.9. (2E,6E)-2,6-Bis((5-methylisoxazol-3-yl)methylene)
cyclohexanone (29)
solid: mp. 188.5e190 ꢀC. IR (neat) nmax: 2940, 1662, 1609, 1566,
1544, 1155 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d
: 1.93 (quin, J ¼ 6.0 Hz,
2H), 2.98 (t, J ¼ 6.0 Hz, 4H), 3.96 (s, 6H), 7.59 (s, 2H), 7.65 (s, 2H),
7.72 (s, 2H). 13C NMR (75 MHz, CDCl3)
: 21.9, 28.4, 39.2,118.8, 127.2,
This compound was prepared by method A in 49% yield as a
yellow crystal: mp. 155e156 ꢀC. IR (neat) nmax: 3129, 2943, 1685,
1636, 1598, 1426, 1267, 1181, 910, 783 cmꢁ1 1H NMR (300 MHz,
.
d
131.7, 132.7, 140.9, 189.0. HR-MS (ESI) m/z: calcd for C16H19N4O
[M þ H]: 283.1559; found 283.1567.
CDCl3)
d
: 2.47 (s, 6H), 2.52 (s, 3H), 3.90 (s, 4H), 6.11 (s, 2H), 7.42 (s,
: 12.2, 45.7, 57.5, 103.6, 121.9, 138.1,
2H). 13C NMR (75 MHz, CDCl3)
d
158.8, 169.9, 186.5. HR-MS (ESI) m/z: calcd for C16H18N3O3 [M þ H]:
4.3.16. (2E,6E)-2,6-Bis((1-methyl-1H-pyrazol-5-yl)methylene)
cyclohexanone (36)
300.1348; found 300.1345.
This compound was prepared by method A in 97% yield as a
4.3.10. (3E,5E)-1-Methyl-3,5-bis((3-methylisoxazol-5-yl)
methylene)piperidin-4-one (30)
This compound was prepared by method A in 36% yield as a
yellow crystal: mp. 162e164 ꢀC. IR (neat) nmax: 3135, 2935, 1679,
1631, 1605, 1600, 1446, 1412, 1273, 1185 cmꢁ1. 1H NMR (300 MHz,
yellow solid: mp.153e154 ꢀC. IR (neat) nmax: 3097, 2943,1664,1607,
1450, 1265, 1172, 923 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d
: 1.87 (quin,
J ¼ 6.3 Hz, 2H), 2.84 (t, J ¼ 6.3 Hz, 4H), 3.97 (s, 6H), 6.47 (s, 2H), 7.51
(s, 2H), 7.66 (s, 2H). 13C NMR (75 MHz, CDCl3)
: 21.6, 28.1, 37.1,
108.3, 122.1, 136.1, 137.5, 138.5, 188.5. HR-MS (ESI) m/z: calcd for
16H19N4O [M þ H]: 283.1559; found 283.1553.
d
CDCl3)
d
: 2.37 (s, 6H), 3.02 (s, 3H), 4.07 (s, 4H), 6.36 (s, 2H), 7.48 (s,
: 11.3, 45.6, 56.6, 109.5, 118.6, 136.0,
2H). 13C NMR (75 MHz, CDCl3)
d
C
160.2, 166.0, 185.9. HR-MS (ESI) m/z: calcd for C16H18N3O3 [M þ H]:
300.1348; found 300.1347.
4.3.17. (2E,6E)-2,6-Bis(thiazole-2-yl methylene)cyclohexanone (37)
This compound was prepared by method A in 84% yield as a
yellow solid: mp. 158.5e159 ꢀC. IR (neat) nmax: 3073, 2929, 1654,
4.3.11. (2E,6E)-2,6-Bis((1-methyl-1H-imidazol-2-yl)methylene)
cyclohexanone (31)
1594, 1562, 1463, 1259, 1178, 737 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d:
This compound was prepared by method A in 72.5% yield as a
1.97 (quin, J ¼ 6.3 Hz, 2H), 3.22 (t, J ¼ 5.4 Hz, 4H), 7.53 (s, 2H), 7.87 (s,
yellow solid: mp. 190e192 ꢀC. IR (neat) nmax: 3129, 3105, 3042,
2H), 8.02 (s, 2H). 13C NMR (75 MHz, CDCl3)
d
: 21.2, 28.7, 122.0, 127.4,
2942, 1663, 1605, 1567, 1505, 1477, 1266, 1176, 742 cmꢁ1
.
1H NMR
138.6, 144.7, 163.5, 189.2. HR-MS (ESI) m/z: calcd for C14H13N2OS2
[M þ H]: 289.0469; found 289.0457.
(300 MHz, CDCl3)
d: 1.89 (quin, J ¼ 6.3 Hz, 2H), 3.37 (t, J ¼ 5.4 Hz,