4136
P. C. Meltzer et al. / Bioorg. Med. Chem. Lett. 13 (2003) 4133–4137
15. Meltzer, P. C.; Liang, A. Y.; Blundell, P.; Gonzalez,
Elemental Analyses
M. D.; Chen, Z.; George, C.; Madras, B. K. J. Med. Chem.
1997, 40, 2661.
16. Meltzer, P. C.; Blundell, P.; Chen, Z.; Yong, Y.; Madras,
B. K. Bioorg. Med. Chem. Lett. 1999, 9, 857.
Biological assays
Calculated
Found
Calculated for
formula
17. Meltzer, P. C.; Blundell, P.; Yong, Y. F.; Chen, Z.;
George, C.; Gonzalez, M. D.; Madras, B. K. J. Med. Chem.
2000, 43, 2982.
Compd
O-506
C
H
N
Cl
C
H
N
Cl
18. Meltzer, P. C.; Wang, B.; Chen, Z.; Blundell, P.; Jayara-
man, M.; Gonzalez, M. D.; George, C.; Madras, B. K. J. Med.
Chem. 2001, 44, 2619.
19. Keverline, K. I.; Abraham, P.; Lewin, A. H.; Carroll, F. I.
Tetrahedron Lett. 1995, 36, 3099.
20. Buckley, T. F.; Rapoport, H. J. Am. Chem. Soc. 1980,
102, 3056.
21. Ding, Y.-S.; Shiue, C.-Y.; Fowler, J. S.; Wolf, A. P.; Ple-
nevaux, A. J. Fluorine Chem. 1990, 48, 189.
7
8
9
56.75 6.91 4.14 10.47 56.60 6.89 3.99 10.64 C16H22O4
.
ClN 0.6H2O
16H22
O4ClN
16H20O4
O-2005
O-2003
58.62 6.76 4.27 10.82 58.39 6.93 4.14 10.66
56.49 6.40 4.12 10.42 56.40 6.09 3.92 10.46
C
C
.
ClN 0.8H2O
O-509 10 55.41 6.60 3.23 8.18 55.36 6.62 3.03 8.37
C20H26O6
.
ClN 1.2H2O
O-2006 11 58.32 6.36 3.40 8.61 58.27 6.37 3.22 8.38 C20H26O6ClN
O-2004 12 56.14 6.12 3.27 8.29 56.07 6.02 3.20 8.55 C20H24O6
22. Billimoria, J. D.; Maclagen, N. F. J. Chem. Soc 1954,
3257.
.
ClN 1.0H2O
C18H25O4N
O-906 13 67.69 7.89 4.39
—
67.60 7.92 4.32
—
23. Oh-e, T.; Miyaura, N.; Suzuki, A. J. Org. Chem. 1993, 58,
2201.
24. Meltzer, P. C.; Blundell, P.; Huang, H.; Liu, S.; Yong,
Y. F.; Madras, B. K. Bioorg. Med. Chem. 2000, 8, 581.
25. Carroll, F. I.; Mascarella, S. W.; Kuzemko, M. A.; Gao,
Y.; Abraham, P.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. J.
Med. Chem. 1994, 37, 2865.
Acknowledgements
26. Kimmel, H. L.; Carroll, F. I.; Kuhar, M. J. Drug Alcohol
Depend. 2001, 65, 25.
The authors would like to thank the National Institute
on Drug Abuse (NIDA) (PM: DA7-8081; DA11542;
BKM: DA 06303, DA 11558, DA00304, RR00168) for
support and for the biological and pharmacological
services provided under DA 7-8076, DA 5-8058, DA 2-
9305 and NIDA’s Intramural Research Program.
27. (2,2-Dimethylbenzo[1,3]dioxol-5-yl)boronic acid (2). Mp
187–189 ꢀC; Rf 0.51 (10% hexanes in EtOAc); 1H NMR d 1.70
(s, 6H), 6.85 (d, 1H), 7.52 (s, 1H), 7.74 (d, 1H); 13C NMR d
25.9, 108.3, 114.2, 118.0, 123.2, 130.5, 147.3, 151.2. (1R)-2-
Carbomethoxy-3-(2,2-dimethylbenzo[1,3]dioxol-5-yl)tropene (4).
Mp71–73 ꢀC; Rf 0.30 (10% MeOH in EtOAc); 1H NMR d
1.55–1.70 (m, 1H), 1.67 (s, 6H), 1.90–2.05 (m, 2H), 2.03 (d,
J=19.2 Hz, 1H), 2.05–2.25 (m, 1H), 2.42 (s, 3H), 2.72 (dd,
J=19.2, 4.7 Hz, 1H), 3.33 (t, J=4.9 Hz, 1H), 3.54 (s, 3H), 4.80
(d, J=4.7 Hz, 1H), 6.55 (s, 1H), 6.57 (d, 1H), 6.66 (d,1H);
(1R)-2ꢀ-Carbomethoxy-3ꢁ-(2,2-dimethylbenzo[1,3]dioxol-5y-
l)trop-ane (6) and (1R)-2ꢀ-carbomethoxy-3ꢀ-(2,2-dimethyl-
benzo [1,3]dioxol-5-yl)tropane (5). 5: Rf 0.85 (10% Et3N in
Et2O); 1H NMR d 1.55–1.75 (m, 3H), 1.64 (s, 3H), 1.65 (s,
3H), 2.02–2.26 (m, 2H), 2.24 (s, 3H), 2.53 (td, J=12.4, 2.7 Hz,
1H), 2.81–2.86 (m, 1H), 2.92 (dt, J=12.9, 4.9 Hz, 1H), 3.34–
3.39 (m, 1H), 3.51–3.57 (m, 1H), 3.53 (s, 3H), 6.58–6.72 (m,
3H). 6: Rf 0.38 (EtOAc); 1H NMR d 1.26 (ddd, 1H), 1.41–1.65
(m, 2H), 1.64 (s, 6H), 2.07–2.25 (m, 2H), 2.24 (s, 3H), 2.40 (dd,
1H), 2.36–2.50 (m, 1H), 3.16–3.33 (m, 3H), 3.60 (s, 3H), 6.58–
6.64 (m, 3H). (1R)-2ꢀ-Carbomethoxy-3ꢀ-(3,4-dihydroxy-
phenyl)tropane hydrochloride (7). Mp228–230 ꢀC; Rf=0.07
(10% Et3N in Et2O); 1H NMR (MeOH-d4) d 1.92 (dt, J=14.8,
2.6 Hz, 1H), 2.13–2.31 (m, 2H), 2.31–2.52 (m, 2H), 2.64 (td,
J=14.8 Hz, 0.8H), 2.85 (s, 3H), 3.01–3.06 (m, 1H), 3.36–3.48
(m, 1H), 3.41 (s, 3H), 3.96–4.05 (m, 1H), 4.07–4.15 (m, 1H),
6.53 (dd, 1H), 6.65 (d,1H), 6.69 (d,1H). (1R)-2ꢀ-Carbo-
methoxy-3ꢁ-(3,4-dihydroxyphenyl)tropane hydrochloride (8).
Mp204–206 ꢀC; Rf 0.15 (10% MeOH in CHCl3); 1H NMR
(MeOH-d4) d 1.94–2.08 (m, 2H), 2.19–2.4 (m, 3H), 2.46–2.58
(m, 1H), 2.81 (s, 3H), 3.21–3.35 (m, 2H), 3.70 (s, 3H), 3.88–
3.95 (m, 1H), 4.09–4.15 (m, 1H), 6.67–6.83 (m, 3H). (1R)-2-
Carbomethoxy-3-(3,4-dihydroxyphenyl)tropene hydrochloride
(9). Mp146–150 ꢀC; Rf 0.13 (10% MeOH in CHCl3); 1H
NMR (MeOH-d4) d 1.90–2.03 (m, 1H), 2.15–2.43 (m, 3H),
2.52 (brd, J=22 Hz, 1H), 2.72 (s, 3H), 2.95 (brd, J=22 Hz,
1H), 3.44 (s, 3H), 3.85 (brs, 1H), 4.34 (brs), 1H), 6.44 (dd,1H),
6.53 (d, 1H), 6.64 (d,1H). (1R)-2ꢀ-Carbomethoxy-3ꢀ-(3,4-dia-
cetoxyphenyl)tropane hydrochloride (10). Mp158–161 ꢀC; Rf
0.35 (10% MeOH in CHCl3); 1H NMR (MeOH-d4) d 1.96–
2.07 (m, 1H), 2.17–2.37 (m, 2H), 2.26 (s, 3H), 2.27 (s, 3H),
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