914
M. I. Rodríguez-Franco, M. I. Fernández-Bachiller
PAPER
13C NMR (CDCl3): = 161.0, 152.1, 151.9, 142.5, 138.2, 129.0,
128.1, 126.9, 121.4, 63.0, 54.1, 52.8, 49.6, 36.3, 29.8.
13C NMR (CDCl3): = 132.1, 130.3, 129.2, 128.9, 65.4, 60.3, 59.7,
35.1, 28.8.
MS (EI): m/z (%) = 91 (100), 246 (93), 337 (23, M+.).
MS (EI): m/z (%) = 91 (100), 97 (35), 188 (15, M+.).
MS (ES, positive mode): m/z = 188 (100%, M+.).
6b
From the fractions of Rf 0.3 (CH2Cl2–MeOH, 5:1) compound 6b
was isolated (52 mg, 14%) as a pure syrup.
Acknowledgement
1H NMR (CDCl3): = 8.52 (s, 1 H), 7.87 (s, 1 H), 7.28 (m, 5 H),
4.21 (t, 2 H, J = 6.8), 4.18 (s, 3 H), 3.61 (d, 1 H, J = 12.9 Hz), 3.57
(d, 1 H, J = 12.9 Hz), 2.78 (dd, 1 H, J = 8.1, 7.2 Hz), 2.65 (ddd, 1
H, J = 8.7, 7.7, 6.6 Hz), 2.51 (ddd, 1 H, J = 8.7, 8.3, 6.2 Hz), 2.15
(dd, 1 H, J = 8.1, 7.0 Hz), 2.10 (m, 1 H), 2.05 (m, 1 H), 1.98 (m, 2
H), 1.46 (ddt, 1 H, J = 12.2, 8.1, 6.1 Hz).
The authors gratefully acknowledge the financial supports of
C.I.C.Y.T. (SAF 99-098) and Comunidad de Madrid (08.5/0045.1/
99) and the fellowship to M. I. Fernández-Bachiller from CSIC-
NeuroPharma, S. A.
13C NMR (CDCl3): = 161.1, 152.0, 141.9, 138.5, 128.8, 128.3,
127.0, 121.5, 60.4, 59.7, 54.2, 53.6, 43.0, 35.7, 34.7, 30.3.
References
(1) This paper comprises a part of M. I. Fernández-Bachiller’s
Ph.D. Thesis.
MS (EI): m/z (%) = 91 (100), 246 (45), 337 (12, M+.).
(2) Sugimoto, H.; Iimura, Y.; Yamanishi, Y.; Yamatsu, K.
Bioorg. Med. Chem. Lett. 1992, 2, 871.
9-(1-Benzylpiperidin-4-ylmethyl)-6-methylsulfanyl-9H-purine
(7a) and 9-[2-(1-Benzylpyrrolidin-3-yl)ethyl]-6-methylsulfanyl-
9H-purine (7b)
From 6-methylsulfanyl-9H-purine (98 mg, 0.59 mmol), chloro de-
rivative 1 (200 mg, 0.76 mmol) and NaH (128 mg, 2.67 mmol), and
following the general method, a syrup was obtained. Its purification
on a silica gel column using CH2Cl2–MeOH (20:1) as eluent yielded
derivatives 7a and 7b. From the fractions of Rf 0.7 (CH2Cl2–MeOH,
5:1) unreacted starting purine was isolated (10 mg, 10%).
(3) Contreras, J.-M.; Rival, Y. M.; Chayer, S.; Bourguignon, J.-
J.; Wermuth, C. G. J. Med. Chem. 1999, 42, 730.
(4) Gilligan, P. J.; Cain, G. A.; Christos, T. E.; Cook, L.;
Drummond, S.; Johnson, A. L.; Kergaye, A. A.; McElroy, J.
F.; Rohrbach, K. W.; Schmidt, W. K.; Tam, S. W. J. Med.
Chem. 1992, 35, 4344.
(5) Boyfield, I.; Brown, T. H.; Coldwell, M. C.; Cooper, D. G.;
Hadley, M. S.; Hagan, J. J.; Healy, M. A.; Johns, A.; King,
R. J.; Middlemiss, D. N.; Nash, D. J.; Riley, G. J.; Scott, E.
E.; Smith, S. A.; Stemp, G. J. J. Med. Chem. 1996, 39, 1946.
(6) Zhou, Z. L.; Cai, S. X.; Whittemore, E. R.; Konkoy, C. S.;
Espitia, S. A.; Tran, M.; Rock, D. M.; Coughenour, L. L.;
Hawkinson, J. E.; Boxer, P. A.; Bigge, C. F.; Wise, L. D.;
Weber, E.; Woodward, R. M.; Keana, J. F. J. Med. Chem.
1999, 42, 2993.
(7) Dutta, A. K.; Coffey, L. L.; Reith, M. E. A. J. Med. Chem.
1997, 40, 35.
(8) Dutta, A. K.; Xu, C.; Reith, M. E. A. J. Med. Chem. 1998,
41, 3293.
(9) Ohrui, H.; Kohgo, S.; Kitano, K.; Sakata, S.; Kodama, E.;
Yoshimura, K.; Matsuoka, M.; Shigeta, S.; Mitsuya, H. J.
Med. Chem. 2000, 43, 4516.
7a
Fractions of Rf 0.6 (CH2Cl2–MeOH, 5:1) afforded compound 7a
(29 mg, 13%) as a pure syrup.
1H NMR (CDCl3): = 8.71 (s, 1 H), 7.88 (s, 1 H), 7.26 (m, 5 H),
4.10 (d, 2 H, J = 7.2 Hz), 3.46 (s, 2 H), 2.86 (br d, 2 H, J = 11.6 Hz),
2.71 (s, 3 H), 1.92 (m, 1 H), 1.90 (dt, 2 H, J = 11.6, 2.2 Hz), 1.55 (br
d, 2 H, J = 12.0 Hz), 1.35 (dq, 2 H, J = 12.0, 3.6 Hz).
13C NMR (CDCl3): = 161.7, 152.0, 148.4, 142.8, 138.1, 131.4,
129.1, 128.2, 127.0, 63.1, 52.8, 49.5, 36.4, 29.8, 11.7.
MS (EI): m/z (%) = 91 (100), 262 (25), 353 (5, M+.).
7b
(10) Hakimelahi, G. H.; Mei, N.-W.; Moosavi-Movahedi, A. A.;
Davari, H.; Hakimelahi, S.; King, K.-Y.; Hwu, J. R.; Wen,
Y.-S. J. Med. Chem. 2001, 44, 1749.
(11) Harada, H.; Asano, O.; Hoshino, Y.; Yoshikawa, S.;
Matsukura, M.; Kabasawa, Y.; Niijima, J.; Kotake, Y.;
Watanabe, N.; Kawata, T.; Inoue, T.; Horizoe, T.; Yasuda,
N.; Minami, H.; Nagata, K.; Murakami, M.; Nagaoka, J.;
Kobayashi, S.; Tanaka, I.; Abe, S. J. Med. Chem. 2001, 44,
170.
(12) Rathbone, M. P.; Middlemiss, P. J.; Gysbers, J. W.; Andrew,
C.; Herman, M. A. R.; Reed, J. K.; Ciccaretti, R.; Di Iorio,
P.; Caciagli, F. Prog. Neurobiol. 1999, 59, 663.
(13) Rodríguez-Franco, M. I.; Dorronsoro, I.; Martínez, A.;
Pérez, C.; Badía, A.; Baños, J. E. Arch. Pharm. (Weinheim)
2000, 333, 118.
(14) Martínez, A.; Fernandez, E.; Castro, A.; Conde, S.;
Rodríguez-Franco, M. I.; Baños, J. E.; Badía, A. Eur. J. Med.
Chem. 2000, 35, 913.
(15) Mitsunobu, O. Synthesis 1981, 1.
(16) Iwakawa, M.; Pinto, B. M.; Szarek, W. A. Can. J. Chem.
1978, 56, 326.
(17) DeVita, R. J.; Goulet, M. T.; Wyvratt, M. J.; Fisher, M. H.;
Lo, J.-L.; Yang, Y. T.; Cheng, K.; Smith, R. G. Bioorg. Med.
Chem. Lett. 1999, 9, 2621.
(18) Rodríguez-Franco, M. I.; Dorronsoro, I.; Martínez, A.
Synthesis 2001, 1711.
Fractions of Rf 0.4 (CH2Cl2–MeOH, 5:1) yielded 7b (60 mg, 29%)
as a colorless syrup.
1H NMR (CDCl3): = 8.70 (s, 1 H), 7.90 (s, 1 H), 7.27 (m, 5 H),
4.20 (t, 2 H, J = 7.3), 3.59 (d, 1 H, J = 12.8 Hz), 3.56 (d, 1 H,
J = 12.8 Hz), 2.74 (dd, 1 H, J = 8.7, 7.2 Hz), 2.71 (s, 3 H), 2.61 (ddd,
1 H, J = 8.8, 8.3, 6.0 Hz), 2.50 (ddd, 1 H, J = 8.8, 8.4, 6.1 Hz), 2.17
(dd, 1 H, J = 8.7, 6.5 Hz), 2.10 (m, 1 H), 2.04 (ddt, 1 H, J = 12.0,
8.3, 6.1 Hz), 1.97 (m, 2 H), 1.47 (ddt, 1 H, J = 12.0, 8.4, 6.0 Hz).
13C NMR (CDCl3): = 161.5, 151.8, 148.2, 142.3, 138.7, 131.3,
128.7, 128.2, 127.0, 60.3, 59.6, 53.6, 42.8, 35.6, 34.6, 30.3, 11.7.
MS (EI): m/z (%) = 91 (100), 262 (38), 353 (13, M+.).
1-Benzyl-1-azoniabicyclo[2.2.1]heptane Chloride (4)
A solution of 1 (50 mg, 0.19 mmol) in anhyd toluene (5 mL) was
refluxed under N2 for 24 h. The reaction mixture was cooled, the
solvent evaporated to dryness and the residual brown syrup sus-
pended in a mixture of CH2Cl2–Et2O (ca. 1:1). Insoluble brown syr-
up was discarded and the supernatant liquid was evaporated to
dryness in vacuo to afford the bicyclic compound 4 as a colorless
syrup (25 mg, 58%).
1H NMR (CDCl3): = 7.58 (m, 2 H), 7.36 (m, 3 H), 5.12 (s, 2 H),
3.95 (m, 2 H), 3.67 (s, 2 H), 3.45 (m, 2 H), 2.84 (br s, 1 H), 2.20 (m,
2 H), 1.70 (m, 2 H).
Synthesis 2002, No. 7, 911–915 ISSN 0039-7881 © Thieme Stuttgart · New York