JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
741
6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 6.25 (1H, d, J ¼ 14.6 Hz), 5.97 (2H, dichloromethane, yield 77%. 1H NMR (400 MHz, CDCl3), d(ppm):
s), 3.56 (4H, m), 1.98 (2H, m), 1.88 (2H, m); 13 C NMR (100 MHz,
7.43 (1H, dd, J ¼ 15.1, 15.2 Hz), 6.98 (1H, d, J ¼ 1.3 Hz), 6.89 (1H, dd,
CDCl3), d(ppm): 164.9, 148.2, 148.2, 141.7, 138.7, 131.0, 125.2,
J ¼ 8.1, 1.3 Hz), 6.78 (1H, d, J ¼ 15.4 Hz), 6.77 (1H, d, J ¼ 8.1 Hz),
122.5, 121.4, 108.5, 105.7, 101.2, 46.4, 45.9, 26.1, 24.3; HRMS (ESI)þ
calculated for C16H17NO3, [M þ H]þ: m/z 272.1281, found 272.1282;
Rf ¼ 0.31 (25%, methanol/dichloromethane).
6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 6.37 (1H, d, J ¼ 14.6 Hz), 5.97 (2H,
s), 3.93 (4H, m), 2.65 (4H, m); 13 C NMR (100 MHz, CDCl3), d(ppm):
165.7, 148.3, 148.2, 143.4, 139.0, 130.8, 125.0, 122.6, 119.1, 108.5,
105.7, 101.3, 48.5, 44.9, 28.0, 27.4; HRMS (ESI)þ calculated for
C16H17NO3S, [M þ H]þ: m/z 304.1002, found 304.1002; Rf ¼ 0.35
(25%, methanol/dichloromethane).
2.2.3.5.4. (2E,4E)-N-((3s,5s,7s)-adamantan-1-yl)-5-(benzo[d][1,3]dioxol-
5-yl)penta-2,4-dienamide (9d). Light yellow solid, purified with 5%
methanol/dichloromethane, yield 81%. 1H NMR (400 MHz, CDCl3),
d(ppm): 7.27 (1H, dd, J ¼ 15.1, 15.2 Hz), 6.96 (1H, d, J ¼ 1.3 Hz), 6.88
(1H, dd, J ¼ 8.1, 1.3 Hz), 6.76 (1H, d, J ¼ 15.4 Hz), 6.74 (1H, d,
J ¼ 8.1 Hz), 6.65 (1H, d, J ¼ 14.6 Hz), 5.96 (2H, s), 5.85 (1H, d,
J ¼ 15.0 Hz), 5.24 (1H, s), 2.09 (3H, m), 2.06 (6H, m), 1.69 (6H, m);
13 C NMR (100 MHz, CDCl3), d(ppm): 165.2, 148.2, 148.1, 140.2,
138.3, 130.9, 124.7, 124.7, 122.4, 108.4, 105.7, 101.2, 52.1, 41.7,
41.7, 36.3, 36.3, 29.4, 29.4, 29.4, 29.4, 29.4; HRMS (ESI)þ calculated
for C22H25NO3, [M þ H]þ: m/z 352.1907, found 352.1906; Rf ¼ 0.35
(25%, methanol/dichloromethane).
2.2.3.5.9.
(2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1–(1,1-dioxidothiomor-
pholino)penta-2,4-dien-1-one (9i). Light yellow solid, purified with
5% methanol/dichloromethane, yield 91%. 1H NMR (400 MHz,
CDCl3), d(ppm): 7.44 (1H, dd, J ¼ 15.1, 15.2 Hz), 6.98 (1H, d,
J ¼ 1.3 Hz), 6.89 (1H, dd, J ¼ 8.1, 1.3 Hz), 6.78 (1H, d, J ¼ 15.4 Hz),
6.77 (1H, d, J ¼ 8.1 Hz), 6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 6.41 (1H, d,
J ¼ 14.6 Hz), 5.97 (2H, s), 3.74 (4H, m), 2.00 (4H, m); 13 C NMR
(100 MHz, CDCl3), d(ppm): 165.6, 148.3, 148.2, 143.9, 139.3, 130.7,
124.8, 122.7, 118.5, 108.5, 105.7, 101.3, 42.5, 39.0, 34.6, 34.5; HRMS
(ESI)þ calculated for C16H17NO5S, [M þ H]þ: m/z 336.0900, found
336.0902; Rf ¼ 0.37 (25%, methanol/dichloromethane).
2.2.3.5.5. (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-morpholinopenta-2,4-
dien-1-one (9e). Light yellow solid, purified with 5% methanol/
dichloromethane, yield 78%. 1H NMR (400 MHz, CDCl3), d(ppm):
7.45 (1H, dd, J ¼ 15.1, 15.2 Hz), 6.98 (1H, d, J ¼ 1.3 Hz), 6.89 (1H, dd,
J ¼ 8.1, 1.3 Hz), 6.78 (1H, d, J ¼ 15.4 Hz), 6.77 (1H, d, J ¼ 8.1 Hz),
6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 6.36 (1H, d, J ¼ 14.6 Hz), 5.97 (2H,
s), 3.70 (4H, m), 3.64 (4H, m); 13 C NMR (100 MHz, CDCl3), d(ppm):
165.7, 148.3, 148.2, 143.4, 139.1, 130.8, 125.0, 122.7, 118.7, 108.5,
105.7, 101.3, 66.8, 66.8, 46.1, 42.3; HRMS (ESI)þ calculated for
C16H17NO4, [M þ H]þ: m/z 288.1230, found 288.1227; Rf ¼ 0.28
(25%, methanol/dichloromethane).
2.2.3.5.10. (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(2-(dimethylamino)e-
thyl)penta-2,4-dienamide (9j). Light yellow solid, purified with 7%
methanol/dichloromethane, yield 69%. 1H NMR (400 MHz, CDCl3),
d(ppm): 7.35 (1H, dd, J ¼ 15.1, 15.2 Hz), 6.97 (1H, d, J ¼ 1.3 Hz), 6.88
(1H, dd, J ¼ 8.1, 1.3 Hz), 6.78 (1H, d, J ¼ 15.4 Hz), 6.77 (1H, d,
J ¼ 8.1 Hz), 6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 6.42 (1H, t, J ¼ 4.6 Hz),
5.97 (2H, s), 5.96 (1H, d, J ¼ 14.7 Hz), 3.46 (2H, q, J ¼ 5.5 Hz), 2.54
(2H, t, J ¼ 6.1 Hz), 2.30 (6H, s); 13 C NMR (100 MHz, CDCl3), d(ppm):
166.2, 148.2, 140.8, 138.7, 130.9, 124.7, 123.2, 122.5, 108.4, 105.7,
101.2, 57.9, 44.9, 36.6, 29.6; HRMS (ESI)þ calculated for
C16H20N2O3, [M þ H]þ: m/z 289.1547, found 289.1545; Rf ¼ 0.37
(25%, methanol/dichloromethane).
2.2.3.5.6. (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-((R)-3-methylmorpholi-
no)penta-2,4-dien-1-one (9f). Light yellow solid, purified with 7%
methanol/dichloromethane, yield 83%. 1H NMR (400 MHz, CDCl3),
d(ppm): 7.45 (1H, dd, J ¼ 15.1, 15.2 Hz), 6.98 (1H, d, J ¼ 1.3 Hz), 6.89
(1H, dd, J ¼ 8.1, 1.3 Hz), 6.78 (1H, d, J ¼ 15.4 Hz), 6.77 (1H, d,
J ¼ 8.1 Hz), 6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 6.36 (1H, d, J ¼ 14.6 Hz),
5.97 (2H, s), 4.19 (2H, m), 3.93 (2H, d, J ¼ 8.1 Hz), 3.73 (1H, d,
J ¼ 11.1 Hz), 3.63 (1H, dd, J ¼ 11.1, 3.1 Hz), 3.47 (1H, td, J ¼ 12.2,
3.1 Hz), 1.35 (3H, d, J ¼ 7.1 Hz); 13 C NMR (100 MHz, CDCl3), d(ppm):
165.7, 148.3, 148.2, 143.4, 139.0, 130.8, 125.1, 122.6, 118.9, 108.5,
105.7, 101.3, 77.0, 70.9, 67.0, 29.6, 15.3; HRMS (ESI)þ calculated for
C17H19NO4, [M þ H]þ: m/z 302.1382, found 302.1385; Rf ¼ 0.30
(25%, methanol/dichloromethane).
2.2.3.5.11. (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N,N-diisobutylpenta-2,4-
dienamide (9k). Light yellow solid, purified with 7% methanol/
dichloromethane, yield 83%. 1H NMR (400 MHz, CDCl3), d(ppm):
7.43 (1H, dd, J ¼ 15.1, 15.2 Hz), 6.99 (1H, d, J ¼ 1.3 Hz), 6.89 (1H, dd,
J ¼ 8.1, 1.3 Hz), 6.78 (1H, d, J ¼ 15.4 Hz), 6.77 (1H, d, J ¼ 8.1 Hz),
6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 6.39 (1H, t, J ¼ 15.1 Hz), 5.97 (2H, s),
3.28 (2H, d, J ¼ 7.7 Hz), 3.19 (2H, d, J ¼ 7.7 Hz), 2.05 (1H, m), 1.95
(1H, m), 0.93 (6H, d, J ¼ 6.5 Hz), 0.89 (6H, d, J ¼ 6.5 Hz); 13 C NMR
(100 MHz, CDCl3), d(ppm): 166.9, 148.2, 148.1, 142.3, 138.3, 131.0,
125.3, 122.4, 120.5, 108.4, 105.7, 101.2, 77.3, 77.0, 76.7, 56.0, 54.6,
29.6, 28.9, 26.9, 20.2, 20.1; HRMS (ESI)þ calculated for C20H27NO3,
[M þ H]þ: m/z 330.2064, found 330.2063; Rf ¼ 0.35 (25%, metha-
nol/dichloromethane).
2.2.3.5.7. (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-((S)-3-methylmorpholi-
no)penta-2,4-dien-1-one (9g). Light yellow solid, purified with 7%
methanol/dichloromethane, yield 73%. 1H NMR (400 MHz, CDCl3),
d(ppm): 7.45 (1H, dd, J ¼ 15.1, 15.2 Hz), 6.98 (1H, d, J ¼ 1.3 Hz), 6.89
(1H, dd, J ¼ 8.1, 1.3 Hz), 6.78 (1H, d, J ¼ 15.4 Hz), 6.77 (1H, d,
J ¼ 8.1 Hz), 6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 6.36 (1H, d, J ¼ 14.6 Hz),
5.97 (2H, s), 4.19 (2H, m), 3.93 (2H, d, J ¼ 8.1 Hz), 3.73 (1H, d,
J ¼ 11.1 Hz), 3.63 (1H, dd, J ¼ 11.1, 3.1 Hz), 3.47 (1H, td, J ¼ 12.2,
3.1 Hz), 1.35 (3H,d, J ¼ 7.1 Hz); 13 C NMR (100 MHz, CDCl3), d(ppm):
165.7, 148.3, 148.2, 143.4, 139.0, 130.8, 125.1, 122.6, 118.9, 108.5,
105.7, 101.3, 77.3, 70.9, 67.0, 29.6, 15.3; HRMS (ESI)þ calculated for
C17H19NO4, [M þ H]þ: m/z 302.1387, found 302.1385; Rf ¼ 0.30
(25%, methanol/dichloromethane).
2.2.3.5.12. (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(4-fluorobenzyl)penta-
2,4-dienamide (9l). Light yellow solid, purified with 7% methanol/
dichloromethane, yield 72%. 1H NMR (400 MHz, CDCl3), d(ppm):
7.40 (1H, dd, J ¼ 15.1, 15.2 Hz), 7.29 ꢂ 7.26 (2H, m), 7.04 ꢂ 6.97 (3H,
m), 6.89 (1H, dd, J ¼ 8.1, 1.3 Hz), 6.78 (1H, d, J ¼ 15.4 Hz), 6.77 (1H,
d, J ¼ 8.1 Hz), 6.71 (1H, dd, J ¼ 15.4, 15.2 Hz), 5.97 (2H, s), 5.92 (1H,
d, J ¼ 15.1 Hz), 5.81 (1H, t, J ¼ 6.1 Hz), 4.51 (2H, d, J ¼ 5.7 Hz); 13 C
NMR (100 MHz, CDCl3), d(ppm): 165.9, 163.4, 160.9, 148.3, 148.2,
141.7, 139.3, 134.1, 134.1, 130.7, 129.5, 129.5, 124.5, 122.7, 122.5,
115.6, 115.4, 108.5, 105.7, 101.3, 43.0; HRMS (ESI)þ calculated for
C19H16FNO3, [M þ H]þ: m/z 326.1187, found 326.1189. Rf ¼ 0.41
2.2.3.5.8. (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-thiomorpholinopenta-
2,4-dien-1-one (9h). Light yellow solid, purified with 5% methanol/ (25%, methanol/dichloromethane).