K. Kumar et al. / European Journal of Medicinal Chemistry 86 (2014) 113e121
117
1H, H2), 6.19 (dd, J ¼ 7.2 Hz, 15.9 Hz, 1H, H3), 6.71 (d, J ¼ 15.9 Hz, 1H,
H4), 6.93e7.71 (m, 13H, 11ArH þ H9 þ H10), 7.76 (s, 1H, triazole-H6),
7.94 (d, J ¼ 8.4 Hz, 2H, eArH); 13C NMR (CDCl3, 75 MHz): 49.6, 58.6,
60.5, 61.2, 63.3, 69.0, 69.8, 71.4, 79.3, 114.3, 115.8, 115.9, 116.2, 118.7,
118.8, 122.2, 125.1, 126.7, 126.8, 128.7, 128.8, 130.7, 132.4, 135.4,
135.5, 143.1, 146.5, 161.8, 188.4. HRMS (ESI-micrOTOF-QII) calcd for
75 MHz): 23.6, 28.4, 32.7, 48.6, 49.7, 58.5, 60.2, 66.7, 69.2, 69.5, 71.1,
76.4, 79.7, 114.9, 117.4, 118.6, 126.3, 126.5, 126.8, 128.2, 129.5, 131.9,
132.5, 134.8, 136.6, 146.4, 146.8, 161.9, 188.5. HRMS (ESI-micrOTOF-
QII) calcd for C42H45FeN5O3 [MþH]þ 724.5272, found 724.5267.
4.1.6. 3-[(1-{2-[4-(3-Ferrocenyl-acryloyl)-phenoxy]-ethyl}-1H-
[1,2,3]triazol-4-ylmethyl)-amino]-1-cyclohexyl-4-styryl-azetidin-2-
one (8f)
C
41H36FFeN5O3 [MþH]þ 722.3751, found 722.3749.
4.1.2. 3-[(1-{2-[4-(3-Fereocenyl-acryloyl)-phenoxy]-ethyl}-1H-
[1,2,3]triazol-4-ylmethyl)-amino]-4-styryl-1-p-tolyl-azetidin-2-one
(8b)
Yield 82%; Brick Red Solid; mp. 116e117 ꢂC; 1H NMR (CDCl3,
300 MHz):
d 1.43e2.25 (m, 10H, cyclohexyl); 3.52e3.55 (m, 1H,
cyclohexyl H), 4.17 (s, 5H, H13), 4.37 (s, 2H, H5), 4.45 (s, 2H, H12), 4.58
(s, 2H, H11), 4.67 (s, 2H, H7), 4.91 (t, J ¼ 6.0 Hz, eNH, exchangeable
with D2O), 5.11e5.27 (m, 3H, H1 þ H8), 5.74 (dd, J ¼ 5.7 Hz, 7.2 Hz,
1H, H2), 6.17 (dd, J ¼ 7.2 Hz, 15.9 Hz, 1H, H3), 6.71 (d, J ¼ 15.9 Hz, 1H,
H4), 6.91e7.66 (m, 9H, 7ArH þ H9 þ H10), 7.75 (s, 1H, triazole-H6),
7.94 (d, J ¼ 8.4 Hz, 2H, eArH); 13C NMR (CDCl3, 75 MHz): 22.1, 27.3,
31.5, 47.4, 49.6, 58.7, 60.4, 66.5, 69.6, 69.8, 71.2, 76.7, 79.3, 114.8,
117.1,118.5,126.2,126.4,126.7, 128.6,129.2,131.8,132.4,134.6,136.9,
146.1, 146.9, 161.4, 188.3. HRMS (ESI-micrOTOF-QII) calcd for
Yield 81%; Brick Red Solid; mp. 114e115 ꢂC; 1H NMR (CDCl3,
300 MHz):
d
2.28 (s, 3H, eCH3), 4.16 (s, 5H, H13), 4.37 (s, 2H, H5),
4.47 (s, 2H, H12), 4.57 (s, 2H, H11), 4.65 (s, 2H, H7), 4.90 (t, J ¼ 6.0 Hz,
eNH, exchangeable with D2O), 5.16e5.29 (m, 3H, H1 þ H8), 5.72
(dd, J ¼ 5.7 Hz, 7.2 Hz, 1H, H2), 6.17 (dd, J ¼ 7.2 Hz, 15.9 Hz, 1H, H3),
6.72 (d, J ¼ 15.9 Hz, 1H, H4), 6.90e7.69 (m, 13H, 11ArH þ H9þH10),
7.75 (s, 1H, triazole-H6), 7.95 (d, J ¼ 8.6 Hz, 2H, eArH); 13C NMR
(CDCl3, 75 MHz): 21.0, 49.7, 58.6, 60.1, 61.1, 66.3, 69.0, 69.8, 71.4,
79.3, 114.3, 117.2, 118.7, 122.4, 125.3, 126.7, 126.8, 128.8, 128.9, 129.6,
129.7, 130.7, 131.3, 132.4, 134.3, 136.5, 146.3, 146.4, 161.1, 188.6.
C
41H43FeN5O3 [MþH]þ 710.7537, found 710.7531.
HRMS (ESI-micrOTOF-QII) calcd for
718.5279, found 718.5275.
C
42H39FeN5O3 [MþH]þ
4.1.7. 3-[(1-{3-[4-(3-Ferrocenyl-acryloyl)-phenoxy]-propyl}-1H-
[1,2,3]triazol-4-ylmethyl)-amino]-1-(4-fluoro-phenyl)-4-styryl-
azetidin-2-one (8g)
4.1.3. 3-[(1-{2-[4-(3-Fereocenyl-acryloyl)-phenoxy]-ethyl}-1H-
[1,2,3]triazol-4-ylmethyl)-amino]-1-(4-chloro-phenyl)-4-styryl-
azetidin-2-one (8c)
Yield 85%; Brick Red Solid; mp. 118e119 ꢂC; 1H NMR (CDCl3,
300 MHz): d
2.34e2.36 (m, 2H, H8), 4.00 (s, 2H, H5), 4.16 (s, 5H, H13),
4.46 (s, 4H, H7 þ H14), 4.58 (s, 2H, H12), 4.89 (t, J ¼ 6.0 Hz, eNH,
exchangeable with D2O), 5.15e5.28 (m, 3H, H1 þ H9), 5.81 (dd,
J ¼ 5.7 Hz, 7.2 Hz, 1H, H2), 6.20 (dd, J ¼ 7.2 Hz, 15.9 Hz, 1H, H3), 6.74
(d, J ¼ 15.9 Hz,1H, H4), 6.89e6.98 (m, 4H, eArH), 7.14 (d, J ¼ 15.9 Hz,
1H, H10), 7.25e7.55 (m, 7H, ꢀArH), 7.64 (s, 1H, triazole-H6), 7.72 (d,
J ¼ 15.9 Hz, 1H, H11), 7.98 (d, J ¼ 8.9 Hz, 2H, eArH); 13C NMR (CDCl3,
75 MHz): 19.2, 47.0, 58.7, 60.5, 64.3, 69.0, 69.8, 71.3, 71.8, 79.4,114.2,
115.9, 116.2, 118.7, 118.8, 122.5, 124.4, 126.7, 126.8, 128.7, 128.8, 130.7,
131.9, 132.7, 135.5, 136.8, 143.0, 146.2, 161.9, 188.2. HRMS (ESI-
micrOTOF-QII) calcd for C42H38FFeN5O3 [MþH]þ 736.1041, found
736.1037.
Yield 79%; Brick Red Solid; mp. 117e118 ꢂC; 1H NMR (CDCl3,
300 MHz): d
4.14 (s, 5H, H13), 4.36 (s, 2H, H5), 4.46 (s, 2H, H12), 4.58
(s, 2H, H11), 4.63 (s, 2H, H7), 4.88 (t, J ¼ 6.0 Hz, eNH, exchangeable
with D2O), 5.14e5.31 (m, 3H, H1 þ H8), 5.71 (dd, J ¼ 5.7 Hz, 7.2 Hz,
1H, H2), 6.17 (dd, J ¼ 7.2 Hz, 15.9 Hz, 1H, H3), 6.73 (d, J ¼ 15.9 Hz, 1H,
H4), 6.89e7.67 (m, 13H, 11ArH þ H9 þ H10), 7.76 (s, 1H, triazole-H6),
7.96 (d, J ¼ 8.4 Hz, 2H, eArH); 13C NMR (CDCl3, 75 MHz): 49.4, 58.5,
60.3, 61.1, 63.5, 69.2, 69.6, 71.5, 79.7, 114.4, 115.6, 115.8, 116.5, 118.4,
118.6, 122.4, 125.2, 126.6, 128.3, 128.5, 128.9, 130.5, 132.3, 135.2,
135.4, 143.5, 146.3, 161.2, 188.9. HRMS (ESI-micrOTOF-QII) calcd for
C
41H36ClFeN5O3 [MþH]þ 738.6192, found 738.6184.
4.1.8. 3-[(1-{3-[4-(3-Ferrocenyl-acryloyl)-phenoxy]-propyl}-1H-
[1,2,3]triazol-4-ylmethyl)-amino]-4-styryl-1-p-tolyl-azetidin-2-one
(8h)
4.1.4. 3-[(1-{2-[4-(3-Ferrocenyl-acryloyl)-phenoxy]-ethyl}-1H-
[1,2,3]triazol-4-ylmethyl)-amino]-1-phenyl-4-styryl-azetidin-2-one
(8d)
Yield 84%; Brick Red Solid; mp. 112e113 ꢂC; 1H NMR (CDCl3,
Yield 82%; Brick Red Solid; mp. 116e117 ꢂC; 1H NMR (CDCl3,
300 MHz):
d
2.30e2.34 (m, 2H, H8), 2.32 (s, 3H, ꢀCH3), 4.01 (s, 2H,
300 MHz):
d
4.14 (s, 5H, H13), 4.35 (s, 2H, H5), 4.48 (s, 2H, H12), 4.55
H5), 4.17 (s, 5H, H13), 4.44 (s, 4H, H7 þ H14), 4.59 (s, 2H, H12), 4.88 (t,
J ¼ 6.0 Hz, eNH, exchangeable with D2O), 5.16e5.27 (m, 3H,
H1 þ H9), 5.80 (dd, J ¼ 5.7 Hz, 7.2 Hz, 1H, H2), 6.22 (dd, J ¼ 7.2 Hz,
15.9 Hz, 1H, H3), 6.75 (d, J ¼ 15.9 Hz, 1H, H4), 6.86e6.95 (m, 4H,
eArH), 7.13 (d, J ¼ 15.9 Hz, 1H, H10), 7.23e7.53 (m, 7H, eArH), 7.62
(s, 1H, triazole-H6), 7.71 (d, J ¼ 15.9 Hz, 1H, H11), 7.98 (d, J ¼ 8.9 Hz,
2H, eArH); 13C NMR (CDCl3, 75 MHz): 19.5, 21.4, 47.6, 58.4, 60.3,
64.7, 69.3, 69.5, 71.6, 71.8, 79.7, 114.1, 115.5, 116.4, 118.6, 118.7, 122.3,
124.5, 126.6, 126.9, 128.5, 128.9, 130.5, 131.8, 132.4, 135.6, 136.9,
143.2, 146.1, 161.4, 188.1. HRMS (ESI-micrOTOF-QII) calcd for
(s, 2H, H11), 4.63 (s, 2H, H7), 4.92 (t, J ¼ 6.0 Hz, eNH, exchangeable
with D2O), 5.14e5.28 (m, 3H, H1 þ H8), 5.70 (dd, J ¼ 5.7 Hz, 7.2 Hz,
1H, H2), 6.19 (dd, J ¼ 7.2 Hz, 15.9 Hz, 1H, H3), 6.74 (d, J ¼ 15.9 Hz, 1H,
H4), 6.93e7.66 (m, 14H, 12ArH þ H9þH10), 7.78 (s, 1H, triazole-H6),
7.93 (d, J ¼ 8.6 Hz, 2H, eArH); 13C NMR (CDCl3, 75 MHz): 49.4, 58.8,
60.6, 66.3, 69.8, 69.9, 71.5, 76.8, 79.6, 114.9, 117.3, 118.6, 126.7, 126.8,
126.9, 128.3, 128.5, 128.7, 129.5, 129.7, 130.5, 131.9, 132.7, 134.8,
136.8, 146.4, 146.6, 161.8, 188.4. HRMS (ESI-micrOTOF-QII) calcd for
C
41H37FeN5O3 [MþH]þ 704.6415, found 704.6411.
C
43H41FeN5O3 [MþH]þ 732.0409, found 732.0401.
4.1.5. 3-[(1-{2-[4-(3-Ferrocenyl-acryloyl)-phenoxy]-ethyl}-1H-
[1,2,3]triazol-4-ylmethyl)-amino]-1-cycloheptyl-4-styryl-azetidin-
2-one (8e)
4.1.9. 3-[(1-{3-[4-(3-Fereocenyl-acryloyl)-phenoxy]-propyl}-1H-
[1,2,3]triazol-4-ylmethyl)-amino]-1-(4-chloro-phenyl)-4-styryl-
azetidin-2-one (8i)
Yield 79%; Brick Red Solid; mp. 115e116 ꢂC; 1H NMR (CDCl3,
300 MHz):
d
1.33e2.26 (m, 12H, cycloheptyl); 3.55e3.59 (m, 1H,
Yield 80%; Brick Red Solid; mp. 119e120 ꢂC; 1H NMR (CDCl3,
cycloheptyl H), 4.16 (s, 5H, H13), 4.39 (s, 2H, H5), 4.46 (s, 2H, H12),
4.58 (s, 2H, H11), 4.63 (s, 2H, H7), 4.92 (t, J ¼ 6.0 Hz, eNH,
exchangeable with D2O), 5.14e5.29 (m, 3H, H1 þ H8), 5.71 (dd,
J ¼ 5.7 Hz, 7.2 Hz, 1H, H2), 6.16 (dd, J ¼ 7.2 Hz, 15.9 Hz, 1H, H3), 6.72
(d, J ¼ 15.9 Hz, 1H, H4), 6.93e7.68 (m, 9H, 7ArH þ H9 þ H10), 7.77 (s,
1H, triazole-H6), 7.94 (d, J ¼ 8.6 Hz, 2H, eArH); 13C NMR (CDCl3,
300 MHz): d
2.32e2.36 (m, 2H, H8), 4.02 (s, 2H, H5), 4.14 (s, 5H, H13),
4.48 (s, 4H, H7 þ H14), 4.59 (s, 2H, H12), 4.88 (t, J ¼ 6.0 Hz, eNH,
exchangeable with D2O), 5.17e5.29 (m, 3H, H1 þ H9), 5.80 (dd,
J ¼ 5.7 Hz, 7.2 Hz, 1H, H2), 6.21 (dd, J ¼ 7.2 Hz, 15.9 Hz, 1H, H3), 6.73
(d, J ¼ 15.9 Hz,1H, H4), 6.88e6.96 (m, 4H, eArH), 7.14 (d, J ¼ 15.9 Hz,
1H, H10), 7.23e7.54 (m, 7H, eArH), 7.66 (s, 1H, triazole-H6),7.74 (d,