Arch. Pharm. Chem. Life Sci. 2007, 340, 569–576
Synthesis of Protozoocidal Diazabicycles
575
carbamate), 2985 (m, C-C-H), 3063 (w, C=C-H). 1H-NMR: d 1.14 (3H,
t, J = 7.0), 1.23 (3H, t, J = 7.0), 4.11 (2H, ABX3), 4.21 (2H, ABX3), 4.75
(2H, AB), 5.37 (1H, ddd, J = 0.8, J = 5.8, J = 8.0), 5.85 (1H, d, J = 11.4),
6.16 (1H, dd, J = 0.8, J = 9.0), 6.94 (1H, dd, J = 8.0, J = 11.4), 7.17 (1H,
m), 7.23 (1H, m), 7.34 (1H, dd, J = 5.8, J = 9.0), 7.38 (1H, m), 7.56
(1H, m). 13C-NMR: d 14.9 (2), 55.0, 60.3 (3JCF = 4.6), 63.2, 63.7, 94.1,
115.9 (2JCF = 21.0), 125.1 (4JCF = 3.5), 125.4 (2JCF = 14.5), 127.1, 130.6
(3JCF = 8.2), 131.3 (3JCF = 4.2), 131.3, 140.6, 146.8, 157.3, 157.5, 161.0
(1JCF = 245.8), 188.9. ESI-MS: 427.1 [M+Na].
Diisopropyl-1-propoxy-2-oxo-6,7-
diazabicyclo[3.2.2]nona-3,8-diene-6,7-dicarboxylate 5c
Obtained from 2c in 42% yield. Mp. 98–998C. IR (KBr disc, cm– 1):
1110 (m, C-O-C, ether), 1633 (m, C=C), 1715 (s, C=O, ketone), 1738
(s, C=O, carbamate), 2984 (m, C-C-H).1H-NMR: d 0.92 (3H, t, J = 7.3),
1.16 (3H, d, J = 6.2), 1.17 (3H, d, J = 6.2), 1.22 (3H, d, J = 6.2), 1.23
(3H, d, J = 6.2), 1.60 (2H, sex, J = 7.3), 3.54 (2H, ABX2), 4.83 (1H, sep,
J = 6.2), 4.88 (1H, sep, J = 6.2), 5.29 (1H, ddd, J = 0.8, J = 5.8, J = 8.0),
5.79 (1H, d, J = 11.4), 5.98 (1H, dd, J = 0.8, J = 9.0), 6.87 (1H, dd, J =
8.0, J = 11.4), 7.25 (1H, dd, J = 5.8, J = 9.0). 13C-NMR: d 11.2, 22.2,
22.4 (2), 22.5, 23.3, 54.6, 66.3, 70.9, 71.2, 94.0, 127.7, 131.3, 140.3,
146.2, 156.9, 157.0, 189.4. ESI-MS: 367.2 [M+H].
Diethyl-1-(p-chlorobenzyloxy)-2-oxo-6,7-
diazabicyclo[3.2.2]nona-3,8-diene-6,7-dicarboxylate 4h
Obtained from 2h in 95% yield. Mp. 86–898C IR (KBr disc, cm– 1):
1093 (m, C-O-C, ether), 1633 (m, C=C), 1722 (s, C=O, ketone/carba-
mate), 2985 (m, C-C-H). 1H-NMR: d 1.14 (3H, t, J = 7.0), 1.22 (3H, t, J
= 7.0), 4.12 (2H, ABX3), 4.20 (2H, ABX3), 4.68 (2H, AB), 5.36 (1H,
ddd, J = 0.8, J = 5.8, J = 8.0), 5.85 (1H, d, J = 11.4), 6.16 (1H, dd, J =
0.8, J = 9.0), 6.93 (1H, dd, J = 8.0, J = 11.4), 7.33 (1H, dd, J = 5.8, J =
9.0), 7.41 (4H, s). 13C-NMR: d 14.9, 15.0, 55.0, 63.3, 63.7, 65.7, 94.2,
127.3, 129.0, 130.3, 131.3, 133.2, 137.5, 140.6, 146.7, 157.4,
157.5, 188.9. ESI-MS: 443.1 [M+Na].
Diisopropyl-1-butoxy-2-oxo-6,7-diazabicyclo[3.2.2]nona-
3,8-diene-6,7-dicarboxylate 5d
Obtained from 2d in 56% yield. Mp. 71–728C. IR (KBr disc, cm– 1):
1110 (m, C-O-C, ether), 1635 (m, C=C), 1715 (s, C=O, ketone), 1727
and 1743 (s, C=O, carbamate), 2983 (m, C-C-H), 3068 (w, C=C-H).
1H-NMR: d 0.91 (3H, t, J = 7.3), 1.16 (3H, d, J = 6.2), 1.17 (3H, d, J =
6.2), 1.21 (3H, d, J = 6.2), 1.22 (3H, d, J = 6.2), 1.39 (2H, sex, J = 7.3),
1.57 (2H, m), 3.58 (2H, ABX2), 4.82 (1H, sep, J = 6.2), 4.88 (1H, sep, J
= 6.2), 5.29 (1H, ddd, J = 0.8, J = 5.8, J = 8.1), 5.79 (1H, d, J = 11.4),
5.98 (1H, dd, J = 0.8, J = 9.0), 6.87 (1H, dd, J = 8.1, J = 11.4), 7.25 (1H,
dd, J = 5.8, J = 9.0). 13C-NMR: d 14.3, 19.5, 22.2, 22.3, 22.4, 22.5,
32.1, 54.6, 64.1, 70.9, 71.2, 94.0, 127.7, 131.4, 140.3, 146.3, 156.9,
157.0, 189.5. ESI-MS: 381.2 [M+H].
Diethyl-1-(p-methoxybenzyloxy)-2-oxo-6,7-
diazabicyclo[3.2.2]nona-3,8-diene-6,7-dicarboxylate 4i
Obtained from 2i in 71% yield. Mp. 97–988C. IR (KBr disc, cm– 1):
1100 (m, C-O-C, ether), 1615 (m, C=C), 1708 (s, C=O, ketone/carba-
mate), 2988 (m, C-C-H), 3060 (w, C=C-H). 1H-NMR: d 1.15 (3H, t, J =
7.0), 1.22 (3H, t, J = 7.0), 3.78 (3H, s), 4.12 (2H, ABX3), 4.21 (2H,
ABX3), 4.60 (2H, AB), 5.35 (1H, ddd, J = 0.8, J = 5.8, J = 8.0), 5.84 (1H,
d, J = 11.4), 6.14 (1H, dd, J = 0.8, J = 9.0), 6.92 (1H, dd, J = 8.0, J =
11.4), 6.93 (2H, AA9XX9), 7.30 (2H, AA9XX9), 7.31 (1H, dd, J = 5.8, J =
9.0). 13C-NMR: d 15.0 (2), 55.0, 56.1, 63.2, 63.6, 66.3, 94.2, 114.7,
127.5, 130.3, 130.5, 131.3, 140.5, 146.4, 157.4, 157.5, 160.0,
189.0. ESI-MS: 439.2 [M+Na].
Diisopropyl-1-benzyloxy-2-oxo-6,7-
diazabicyclo[3.2.2]nona-3,8-diene-6,7-dicarboxylate 5e
Obtained from 2e in 91% yield. Mp. 99–1008C. IR (KBr disc, cm–1):
1104 (m, C-O-C, ether), 1634 (m, C=C), 1710 (s, C=O, ketone), 1742
(s, C=O, carbamate), 2984 (m, C-C-H). 1H-NMR: d 1.15 (3H, d, J =
6.2), 1.18 (3H, d, J = 6.2), 1.22 (3H, d, J = 6.2), 1.24 (3H, d, J = 6.2),
4.68 (2H, AB), 4.86 (1H, sep, J = 6.2), 4.92 (1H, sep, J = 6.2), 5.35 (1H,
ddd, J = 0.8, J = 5.8, J = 8.1), 5.84 (1H, d, J = 11.4), 6.16 (1H, dd, J =
0.8, J = 9.0), 6.93 (1H, dd, J = 8.1, J = 11.4), 7.32 (1H, dd, J = 5.8, J =
9.0), 7.35 (5H, m). 13C-NMR: d 22.1, 22.2, 22.4, 22.5, 54.8, 66.5,
71.1, 71.4, 94.1, 127.5, 128.3, 128.6, 129.0, 131.4, 138.5, 140.5,
146.6, 158.0 (2), 189.1. ESI-MS: 437.1 [M+Na].
Diisopropyl-1-methoxy-2-oxo-6,7-
diazabicyclo[3.2.2]nona-3,8-diene-6,7-dicarboxylate 5a
Obtained from 2a in 53% yield. Mp. 144–1468C. IR (KBr disc,
cm–1): 1114 (m, C-O-C, ether), 1634 (m, C=C), 1715 (s, C=O, ketone/
carbamate), 2984 (m, C-C-H), 3062 (w, C=C-H). 1H-NMR: d 1.16 (3H,
d, J = 6.2), 1.17 (3H, d, J = 6.2), 1.22 (3H, d, J = 6.2), 1.23 (3H, d, J =
6.2), 3.35 (3H, s), 4.83 (1H, sep, J = 6.2), 4.89 (1H, sep, J = 6.2), 5.30
(1H, ddd, J = 0.8, J = 5.8, J = 8.0), 5.79 (1H, d, J = 11.4), 5.99 (1H, dd, J
= 0.8, J = 9.0), 6.88 (1H, dd, J = 8.0, J = 11.4), 7.27 (1H, dd, J = 5.8, J =
9.0). 13C-NMR: d 22.2, 22.3, 22.4, 22.5, 51.7, 54.6, 70.9, 71.2, 94.3,
127.3, 131.3, 140.3, 146.6, 156.9, 157.0, 189. ESI-MS: 339.2 [M+H].
Diisopropyl-1-(p-fluorobenzyloxy)-2-oxo-6,7-
diazabicyclo[3.2.2]nona-3,8-diene-6,7-dicarboxylate 5f
Obtained from 2f in 80% yield. Mp. 120–1218C. IR (KBr disc,
cm–1): 1107 (m, C-O-C, ether), 1634 (m, C=C), 1719 (s, C=O, ketone/
carbamate), 2980 (m, C-C-H), 3061 (w, C=C-H). 1H-NMR: d 1.15 (3H,
d, J = 6.2), 1.17 (3H, d, J = 6.2), 1.22 (3H, d, J = 6.2), 1.23 (3H, d, J =
6.2), 4.66 (2H, AB), 4.85 (1H, sep, J = 6.2), 4.91 (1H, sep, J = 6.2), 5.35
(1H, ddd, J = 0.8, J = 5.8, J = 8.0), 5.84 (1H, d, J = 11.4), 6.16 (1H, dd, J
Diisopropyl-1-ethoxy-2-oxo-6,7-diazabicyclo[3.2.2]nona-
= 0.8, J = 9.0), 6.93 (1H, dd, J = 8.0, 11.4), 7.17 (2H, dd, J = 8.6, 3JHF
=
8.8), 7.32 (1H, dd, J = 5.8, J = 9.0), 7.43 (2H, dd,4JHF = 5.7, J = 8.6).13C-
NMR: d 22.2, 22.3, 22.4, 22.5, 54.8, 65.8, 71.2, 71.4, 94.1, 115.8
(2JCF = 21.2), 127.4, 130.7 (3JCF = 8.1), 131.3, 134.7 (4JCF = 2.9), 140.6,
146.6, 156.9, 157.0, 162.6 (1JCF = 244.1), 189.0. ESI-MS: 455.1
[M+Na].
3,8-diene-6,7-dicarboxylate 5b
Obtained from 2b in 70% yield. Mp. 128–1308C. IR (KBr disc,
cm– 1): 1112 (m, C-O-C, ether), 1636 (m, C=C), 1715 (s, C=O,
1
ketone/carbamate), 2983 (m, C-C-H). H-NMR: d 1.16 (3H, d, J =
6.2), 1.17 (3H, d, J = 6.2), 1.20 (3H, t, J = 7.1), 1.22 (3H, d, J = 6.2),
1.23 (3H, d, J = 6.2), 3.64 (2H, ABX3), 4.83 (1H, sep, J = 6.2), 4.88 (1H,
sep, J = 6.2), 5.29 (1H, ddd, J = 0.8, J = 5.8, J = 8.0), 5.78 (1H, d, J =
11.4), 5.98 (1H, dd, J = 0.8, J = 9.0), 6.87 (1H, dd, J = 8.0, J = 11.4),
7.24 (1H, dd, J = 5.8, J = 9.0). 13C-NMR: d 15.9, 22.2, 22.3, 22.4, 22.5,
54.6, 60.2, 70.9, 71.2, 94.1, 128.0, 131.3, 140.3, 146.2, 156.9 (2),
189.4. ESI-MS: 353.2 [M+H].
Diisopropyl-1-(o-fluorobenzyloxy)-2-oxo-6,7-
diazabicyclo[3.2.2]nona-3,8-diene-6,7-dicarboxylate 5g
Obtained from 2g in 82% yield. Mp. 118–1198C. IR (KBr disc,
cm–1): 1099 (m, C-O-C, ether), 1633 (m, C=C), 1705 (s, C=O,
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