JOURNAL OF CHEMICAL RESEARCH 2013 349
−
1
1
1
408, 1369, 1274, 1187, 832 cm ; H NMR (400 MHz) δ 1.26 (d,
N-[(3-Methylisoxazole-5-carbonyl)amino]-5-exo-(6-chloropyridin-
J = 3.6 1H, H ), 1.31 (s, 9H, t-butyl), 1.52 (d, J = 10.4 1H, H ), 1.687
3-yl)-7-oxabicyclo[2.2.1]heptane-2-exo,3-exo-dicarboximide (10c):
7a
7s
(
brs, 1H, H ), 1.82–1.87 (m, 1H, H ), 1.90 (d, J = 10.4 Hz, 1H, H ),
Colourless crystals, 25% yield; m.p. 234 °C; R = 0.27 (3:1 ethyl
5n
6x
6n
f
2
.86–2.87 (m, 1H, H ), 2.98 (brs, 1H, H ), 3.15–3.19(m, 2H, H and
acetate/n-hexane); FTIR (ATR): ν 3202, 3009, 2960, 2929, 1795,
1
4
2
H ), 3.78 (s, 3H, OCH ), 6.82 (d, J = 8.2 Hz, 2H, H ), 7.13 (d, J = 8.5
1730, 1702, 1611, 1587, 1512, 1457, 1411, 1292, 1268, 1212, 1196,
1181, 826, 795 cm ; H NMR (500 MHz) δ 1.90–1.95 (dt, J = 5.0;
3
3
aro
−
1 1
Hz, 2H, H ), 7.38 (d, J = 8.7 Hz, 2H, H ), 7.75(d, J = 8.7 Hz, 2H,
aro
aro
13
H ), 8.54 (s, 1H, NH) ppm; C NMR (100 MHz) δ 31.9, 35.0, 39.2,
10.4 Hz, 1H, H6x), 2.37 (s, 3H, CH
12.9 Hz, 1H, H6n), 3.43–3.47 (m, 2H, H
3
), 2.47–2.52 (dd, J = 9.1;
and H ), 3.50–3.51 (m, 1H,
), 7.05 (s, 1H,
aro
3
9.8, 40.9, 46.2, 47.1, 55.30, 113.8, 125.7, 127.6, 128.1, 137.15 (C-t-
2
3
butyl), 156.3 and 157.8 (2C, C-sbst), 165.1 (C–OCH ), 175.2 (1C,
H
5n), 4.71 (s, 1H, H
4
), 5.04 (d, J = 5.3 Hz, 1H, H
1
3
+
C=O), 175.6 (2C, C=O) ppm; GC-MS for C H N O : 446 (M ), 340,
=CH), 7.40 (d, J = 8.1 Hz, 1H, Haro), 7.28–7.29 (dd, J = 2.5; 8.1 Hz,
1H, Haro), 8.34 (d, J = 2.5 Hz, 1H, Haro), 10.55 (brs, 1H, –NH) ppm;
27
30
2
4
1
61; Anal. Calcd for C H N O : C, 72.62; H, 6.77; N, 6.27. Found:
27 30 2 4
13
C, 72.48; H, 6.93; N, 6.21%.
N-[(4-tert-Butyl)benzoylamino]-5-exo-(6-chloro-3-pyridyl)bicyclo[2.2.1]-
heptane-2-endo,3-endo-dicarboximide (9c): Colourless crystals, 65%
C NMR (125 MHz) δ 11.2, 40.3, 44.5, 48.9, 49.1, 80.1, 85.4, 109.8
(=CH), 124.9, 138.9, 149.8, 158.0, 161.6, 161.7, 162.0, 173.4 (1C,
C=O), 173.7 (1C, C=O), 176.0 (1C, C=O) ppm; GC-MS for
+
yield; m.p. 127 °C; R = 0.63 (3:1 ethyl acetate/n-hexane); FTIR
C
18
H
15ClN
Calcd for C18
H, 3.61; N, 14.11%.
4
O
5
: 402(M ), 387, 348, 292, 257, 207, 161, 98, 68); Anal.
f
(
1
ATR): ν 3249, 2962, 2906, 2875, 1725, 1690, 1611, 1525, 1457,
412, 1364, 1275, 1189, 824 cm ; H NMR (400 MHz) δ 1.16–1.28
H15ClN O : C, 53.67; H, 3.75; N, 13.91. Found: C, 53.74;
4 5
−1 1
(
m, 1H, H ), 1.32–1.47 (m, 10H, H and t-butyl), 1.63 (d, J = 10.5 Hz,
N-[(3-Methylisoxazole-5-carbonyl)amino]-5-exo-(2-thienyl)-7-
oxabicyclo[2.2.1]heptane-2-exo,3-exo-dicarboximide (10d): Colour-
7a
7s
1
H, H ), 1.77–1.73 (m, 1H, H ), 1.83 (d, J = 10.5 Hz, 1H, H ), 2.92
6x
5n
6n
(
d, J = 4.8 Hz, 1H, H ), 2.97 (brs, 1H, H ), 3.24 (dt, J = 8.5, 22.5 Hz,
less crystals, 64% yield; m.p. 194–195 °C; R = 0.58 (3:1 ethyl ace-
f
1
4
2
H, H and H ), 7.23 (d, J = 8.2 Hz, 1H, H ), 7.42 (d, J = 8.5 Hz, 2H,
tate/n-hexane); FTIR (ATR): ν 3279, 3105, 3009, 2977, 2949, 1796,
2
3
aro
H ), 7.48–7.51 (m, 1H, H ), 7.80 (d, J = 8.5 Hz, 2H, H ), 8.23 (s,
1720, 1695, 1611, 1586, 1504, 1471, 1441, 1421, 1409, 1294, 1267,
aro
aro
aro
13
−1 1
1
3
1
H, H ), 8.96 (s, 1H, NH) ppm; C NMR (100 MHz) δ 31.0, 35.1,
1205, 1195, 1177, 822, 804 cm ; H NMR (500 MHz) δ 1.95–2.00
(dt, J = 5.0; 10.4 Hz, 1H, H6x), 2.36 (s, 3H, CH ), 2.44–2.49 (dd,
J = 9.1; 12.9 Hz, 1H, H6n), 3.38 (d, J = 7.2, 1H, H ), 3.48 (d, J =
7.2, 1H, H ), 3.68–3.71 (dd, J = 4.4; 9.1 Hz, 1H, H5n), 4.64 (s, 1H,
H ), 4.98 (d, J = 5.3 Hz, 1H, H ), 6.93–6.96 (m, 2H, H ), 7.04 (s,
aro
8.9, 39.3, 39.9, 45.2, 46.2, 46.9, 123.9, 125.7, 127.6, 134.7, 138.1,
48.2 (C-t-butyl), 148.3 and 149.1 (2C, Csubst.), 156.5 (C–Cl), 165.5
3
2
(
(
1C, C=O), 174.7 (2C, C=O), ppm; GC-MS for C H ClN O : 452
3
25
26
3
3
+
M ), 340, 161,73; Anal. Calcd for C H ClN O : C, 66.44; H, 5.80;
4
1
aro
25
26
3
3
1
–
8
H, =CH), 7.28–7.29 (dd, J = 0.9; 4.7 Hz, 1H, H ), 8.74 (brs, 1H,
aro
13
N, 9.30. Found: C, 66.52; H, 5.64; N, 9.10%.
N-[(4-tert-Butyl)benzoylamino]-5-exo-(2-thienyl)bicyclo[2.2.1]heptane-
NH) ppm; C NMR (125 MHz) δ 11.2, 41.0, 43.3, 48.7, 48.7, 79.9,
6.0, 109.8 (=CH), 124.9, 127.4, 139.1, 153.5, 158.5, 160.3, 161.7
2
-endo,3-endo-dicarboximide (9d): Colourless crystals, 68% yield;
(
1C, C=O), 173.5 (1C, C=O), 173.7 (1C, C=O) ppm; GC-MS for
C H N O S: 373(M ), 359, 349, 319, 303, 249, 236, 207, 179, 150,
m.p. 134 °C; R = 0.61 (3:1 ethyl acetate/n-hexane); FTIR (ATR):
f
+
ν 3254, 2964, 2908, 2873, 1725, 1688, 1609, 1526, 1456, 1404, 1364,
17 15
3
5
−
1
1
123, 98, 68; Anal. Calcd for C H N O S: C, 54.68; H, 4.05; N, 11.25.
1
1
273, 1183, 829 cm ; H NMR (400 MHz) δ 1.09–1.18 (m, 1H, H ),
17 15 3 5
7a
Found: C, 54.52; H, 4.21; N, 11.01%.
N-[(3-Methylisoxazole-5-carbonyl)amino]-5-exo-(4-chlorophenyl)-
.22–1.26 (m, 10H, H and t-butyl), 1.50 (d, J = 9.7 Hz, 1H, H ), 1.79
7
s
6x
(
dt, J = 3.9, 13.6 Hz, 1H, H ), 1.90 (d, J = 9.7 Hz, 1H, H ), 2.81–2.84
5
n
6
n
7-oxabicyclo[2.2.1]heptane-2-exo,3-exo-dicarboximide (10e): Colour-
(
m, 2H, H and H ), 3.07–3.10 (m, 2H, H and H ), 6.73 (d, J = 3.9 Hz,
1 4 2 3
less crystals, 36% yield; m.p. 222–223 °C; R = 0.60 (3:1 ethyl
1
H, H ), 6.83 (dd, J = 3.9, 8.7 Hz, 1H, H ), 7.05 (d, J = 3.9 Hz, 1H,
f
aro
aro
acetate/n-hexane); FTIR(ATR): ν 3249, 3126, 3009, 2958, 2932,
H ), 7.27 (d, J = 8.7 Hz, 2H, H ), 7.64 (d, J = 8.7 Hz, 2H, H ), 8.69
aro
aro
aro
13
1795, 1728, 1700, 1617, 1591, 1506, 1463, 1438, 1412, 1298, 1267,
(
s, 1H, NH) ppm; C NMR (100 MHz) δ 31.3, 35.1, 35.3, 38.1, 39.7,
−
1
1
1
194, 1179, 820, 812 cm ; H NMR (500 MHz) δ 1.93–1.97 (dt,
4
1
4.6, 46.5, 46.8, 123.4, 123.6, 125.8, 127.0, 127.7, 138.7, 149.8 and
J = 5.0; 10.4 Hz, 1H, H ), 2.28–2.32 (dd, J = 9.1; 12.9 Hz, 1H,
6x
56.6 (3C, Csubst.), 165.3 (C=O), 175.4 (2C, C=O) ppm; GC-MS for
+
H
6n), 2.39 (s, 3H, CH
), 3.04–3.07 (dd, J = 5.0; 9.1 Hz, 1H, H5n),
3
C H N O S: 422 (M ), 340, 161, 73; Anal. Calcd for C H N O S:
24
26
2
3
24 26
2
3
3
.17 (d, J = 7.2 Hz, 1H, H ), 3.22 (d, J = 7.2 Hz, 1H, H ), 4.84
2
3
C, 68.22; H, 6.20; N, 6.63. Found: C, 68.31; H, 6.24; N, 5.94%.
N-[(3-Methylisoxazole-5-carbonyl)amino]-5-exo-phenyl-7-oxabicyclo-
(
s, 1H, H ), 5.10 (d, J = 5.0 Hz, 1H, H ), 6.87 (s, 1H, =CH), 7.16 (d,
4
1
J = 8.1 Hz, 2H, H ), 7.25–7.27 (t, J = 3.7; 8.1 Hz, 2H, H ), 8.74
aro
aro
[2.2.1]heptane-2-exo,3-exo-dicarboximide (10a): Colourless crystals,
13
(
4
(
4
brs, 1H, –NH) ppm; C NMR (125 MHz) δ 11.2, 40.5, 47.0, 48.9,
9.3, 80.0, 85.6, 109.8 (=CH), 129.3, 129.9, 132.6, 144.9, 161.7
C=O), 173.5 (C=O), 173.8 (C=O) ppm.; GC-MS for C H ClN O :
7
7% yield; m.p. 205–207 °C; R = 0.48 (3:1 ethyl acetate/n-hexane);
f
FTIR (ATR): ν 3213, 3130, 3009, 2980, 1798, 1728, 1607, 1590,
−
1
1
19 16
3
5
1
508, 1495, 1446, 1412, 1296, 1265, 1193, 748, 700 cm ; H NMR
+
01 (M ), 362, 292, 277, 233, 220, 207, 191, 167, 127, 98, 68; Anal.
(
500 MHz) δ 1.86–1.90 (dt, J = 5.0;10.4 Hz, 1H, H ), 2.16–2.22
6x
Calcd for C H ClN O : C, 56.80; H, 4.01; N, 10.46. Found: C, 56.93;
19
16
3
5
(
m, 1H, H ), 2.29 (s, 3H, CH ), 2.96–2.98 (dd, J = 5.0; 9.1 Hz,
6
n
3
H, 3.94; N, 10.37%.
1
1
H, H ), 3.07–3.13 (dd, J = 7.2; 23.9 Hz, 2H, H and H ), 4.78 (s,
5n 2 3
N-[(3-Methylisoxazole-5-carbonyl)amino]-5-exo-(3-methylisoxazol-
-yl)-7-oxabicyclo[2.2.1]heptane-2-exo,3-exo-dicarboximide (10f):
H, H ), 4.99 (d, J = 5.0 Hz, 1H, H ), 6.76 (s, 1H, =CH), 7.10–7.12
4
1
5
13
(
m, 3H, H ), 7.17–7.20 (m, 2H, H ), 9.19 (brs, 1H, –NH) ppm; C
a
r
o
a
r
o
Colourless crystals, 42% yield; m.p. 200 °C(decomp); R = 0.45 (5:1
f
NMR (125 MHz) δ 11.4, 40.1, 47.2, 48.3, 48.7, 79.2, 84.7, 109.8
=CH), 126.9, 127.0, 128.7, 143.6, 153.6 and 160.4 (3C, C-subst)
60.8 (1C, C=O) 172.4 (1C, C=O), 172.7 (1C, C=O) ppm; GC-MS for
C H N O : 354 (M-CH ), 121, 103, 95, 79, 55; Anal. Calcd for
ethyl acetate/n-hexane); FTIR (ATR): ν 3182, 3130, 3009, 2968, 2931,
(
1
1
1
2
1
797, 1733, 1699, 1604, 1512, 1497, 144, 1416, 1267, 1218, 1198,
−1
1
179, 836, 794 cm ; H NMR (500 MHz) δ 2.06–2.08 (m, 1H, H ),
6x
19
17
3
5
3
.21 (s, 3H, CH ), 2.37 (s, 3H, CH ), 2.39–2.44 (dd, J = 9.1;
3
3
C H N O : C, 61.12; H, 4.66; N, 11.44. Found: C, 61.35; H, 4.49; N,
19
17
3
5
2.9 Hz, 1H, H ), 3.42–3.43 (m, 1H, H ), 3.53–3.57 (m, 2H, H
6n
5n
2
1
1.65%.
N-[(3-Methylisoxazole-5-carbonyl)amino]-5-exo-(4-methoxyphenyl)-
-oxabicyclo[2.2.1] heptane-2-exo,3-exo-dicarboximide (10b):
and H ), 4.87 (s, 1H, H ), 4.98 (d, J = 5.3 Hz, 1H, H ), 6.14 (s, 1H,
3
4
1
13
=
(
CH), 7.05 (s, 1H, =CH), 10.55 (brs, 1H, –NH) ppm; C NMR
125 MHz) δ 11.2, 11.2, 36.6, 40.3, 48.7, 48.7, 80.0, 83.4, 102.2
(=CH), 109.8 (=CH), 146.9, 146.3, 160.4, 161.1, 161.7 (1C, C=O),
74.4 (1C, C=O), 175.1 (1C, C=O) ppm. GC-MS for C H N O : 372
7
Colourless crystals, 56% yield; m.p. 118–119 °C; R = 0.58 (4:1 ethyl
f
acetate/n-hexane); FTIR (ATR): ν 3215, 3126, 3009, 2956, 2928,
1
+
17
16
4
6
1
1
796, 1728, 1702, 1611, 1586, 1511, 1463, 1444, 1412, 1294, 1246,
194, 1177, 824, 783 cm ; H NMR (500 MHz) δ 1.87–1.91 (dt,
(
M ), 264, 248, 177, 163, 149, 123, 97, 58;Anal. Calcd for C H N O :
17 16 4 6
−1
1
C, 54.84; H, 4.33; N, 15.05. Found: C, 54.78; H, 4.49; N, 14.94%.
J = 5.0; 10.4 Hz, 1H, H ), 2.17–2.22 (m, 1H, H ), 2.32 (s, 3H,
6x
6n
CH ), 2.95–2.97 (dd, J = 5.0; 9.1 Hz, 1H, H ), 3.09–3.15 (dd,
3
5n
Received 15 January 2013; accepted 4 April 2013
Paper 1301728 doi: 10.3184/174751913X13686357345579
Published online: 12 June 2013
J = 7.2; 24.5 Hz, 2H, H and H ), 3.71(s, 3H, CH ), 4.76 (s, 1H,
2
3
3
H ), 5.01 (d, J = 5.0 Hz, 1H, H ), 6.74 (d, J = 8.8 Hz, 2H, H ), 6.80
4
1
aro
(
s, 1H, =CH), 7.07 (d, J = 8.8 Hz, 2H, H ), 8.68 (brs, 1H, –NH)
aro
13
ppm; C NMR (125 MHz) δ 11.4, 40.1, 46.5, 48.3, 48.7, 55.2 (OCH ),
3
7
1
9.2, 84.9, 109.8 (=CH), 114.0, 128.1, 135.8, 153.5, 158.5, 160.3,
References
60.8 (1C, C=O), 172.3 (1C, C=O), 172.6 (1C, C=O) ppm. LC-MSD
1
2
D. Mitchell and H. Yu, Curr. Opin. Drug Discov. Devel., 2003, 6, 876.
Z.L. Wei, C. George and A.P. Kozikowski, Tetrahedron Lett., 2003, 44,
3847.
+
m/z (relative intensity): 398 (M , 100); Anal. Calcd for C H N O : C,
20
19
3
6
6
0.45; H, 4.82; N, 10.57. Found: C, 60.42; H, 4.99; N, 10.38%.