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A. S. Voisin et al. / Tetrahedron 62 (2006) 11734–11739
1019, 898, 803, 698, 647 cmꢀ1. 1H NMR (400 MHz, CDCl3):
3.3.7. 2-[5-(Pyridin-3-yloxy)pyridin-3-yl]benzonitrile
(12). 2-[5-(Pyridin-3-yloxy)pyridin-3-yl]benzonitrile was
prepared as a white solid (45%) using 5-(pyridin-3-yloxy)-
pyridin-3-yl boronic acid 1 and 2-bromobenzonitrile accord-
ing to general procedure 2. Mp 124 ꢁC. IR (KBr): 3026,
2218, 1591, 1574, 1476, 1416, 1229, 1096, 1021, 893,
d¼9.98 (s, 1H), 8.61 (d, J¼2.3, 1H), 8.41 (d, J¼2.3, 1H),
3
8.38–8.33 (m, 2H), 7.90 (part A of systAB, JAB¼8.3,
2H), 7.64 (part B of systAB, 3JAB¼8.3, 2H), 7.48 (t, J¼2.3,
3
1H), 7.33 (part A of systAB, JAB¼8.3, J¼2.7, 1.4, 1H),
3
7.27 (part B of systAB, JAB¼8.3, J¼4.6, 1H). 13C NMR
1
(100 MHz, CDCl3): d¼191.4, 153.2, 152.6, 145.4, 143.5,
142.4, 141.4, 140.6, 136.4, 134.5, 130.3 (2C), 127.7 (2C),
125.9, 124.3, 123.8. Anal. Calcd for C17H12N2O2: C,
73.90; H, 4.38; N, 10.14. Found: C, 73.66; H, 4.35; N, 10.07.
790, 703 cmꢀ1. H NMR (400 MHz, DMSO-d6): d¼8.69
(s, 1H), 8.64 (d, J¼1.9, 1H), 8.58 (d, J¼1.9, 1H), 8.50 (d,
J¼4.4, 1H), 8.06 (d, J¼7.8, 1H), 7.91–7.87 (m, 2H), 7.79
(d, J¼7.8, 1H), 7.73–7.66 (m, 2H), 7.55–7.51 (m, 1H). 13C
NMR (100 MHz, DMSO-d6): d¼152.5, 152.4, 145.4, 144.5,
141.1, 140.1, 139.2, 134.7, 133.8, 133.7, 130.4, 129.2, 126.0,
125.9, 124.8, 118.1, 110.7. Anal. Calcd for C17H11N3O: C,
74.71; H, 4.06; N, 15.38. Found: C, 74.66; H, 4.09; N, 15.13.
3.3.4. 4-[5-(5-Chloropyridin-3-yloxy)pyridin-3-yl]benz-
aldehyde (9). 4-[5-(5-Chloropyridin-3-yloxy)pyridin-3-yl]-
benzaldehyde was prepared as an orange solid (66%) using
5-(5-chloropyridin-3-yloxy)pyridin-3-yl boronic acid 2 and
4-bromobenzaldehyde according to general procedure 2.
Mp 110 ꢁC. IR (KBr): 1694, 1606, 1572, 1440, 1421, 1296,
3.3.8. 4-[5-(Pyridin-3-yloxy)pyridin-3-yl]benzonitrile
(13). 4-[5-(Pyridin-3-yloxy)pyridin-3-yl]benzonitrile was
prepared as an orange solid (78%) using 5-(pyridin-3-yloxy)-
pyridin-3-yl boronic acid 1 and 4-bromobenzonitrile
according to general procedure 2. Mp 128 ꢁC. IR (KBr):
3052, 2222, 1604, 1569, 1473, 1425, 1217, 1105, 1016, 893,
1246, 1219, 1094, 935, 823, 698, 684 cmꢀ1 1H NMR
.
(400 MHz, CDCl3): d¼9.98 (s, 1H), 8.66 (d, J¼1.8, 1H),
8.39 (d, J¼1.8, 1H), 8.31 (d, J¼2.4, 1H), 8.28 (d, J¼2.4,
3
1H), 7.91 (part A of systAB, JAB¼8.1, 2H), 7.66 (part B
3
1
of systAB, JAB¼8.1, 2H), 7.52 (t, J¼1.8, 1H), 7.31 (t,
802, 702 cmꢀ1. H NMR (400 MHz, CDCl3): d¼8.51 (d,
J¼2.4, 1H). 13C NMR (100 MHz, CDCl3): d¼191.3, 153.0,
152.4, 144.1, 143.9, 142.0, 140.8, 138.7, 136.6, 135.9,
131.9, 130.3 (2C), 127.7 (2C), 125.3, 124.5. Anal. Calcd
for C17H11ClN2O2: C, 65.71; H, 3.57; N, 9.01. Found: C,
65.56; H, 3.35; N, 8.92.
J¼1.7, 1H), 8.34–8.29 (m, 3H), 7.62 (part A of systAB,
3JAB¼6.6, J¼1.7, 1.7, 2H), 7.53 (part B of systAB,
3JAB¼6.6, J¼1.7, 1.7, 2H), 7.48 (d, J¼1.7, 1H), 7.28 (part
3
A of systAB, JAB¼8.4, J¼2.7, 1.4, 1H), 7.22 (part B of
3
systAB, JAB¼8.4, J¼4.6, 1H). 13C NMR (100 MHz,
CDCl3): d¼153.2, 152.5, 145.3, 143.1, 141.2, 140.9, 140.6,
135.8, 132.7 (2C), 127.7 (2C), 125.9, 124.3, 123.6, 118.1,
112.1. Anal. Calcd for C17H11N3O: C, 74.71; H, 4.06; N,
15.18. Found: C, 74.55; H, 3.99; N, 14.89.
3.3.5. 2-[6-(Pyridin-3-yloxy)pyridin-3-yl]benzaldehyde
(10). 2-[6-(Pyridin-3-yloxy)pyridin-3-yl]benzaldehyde was
prepared as an orange solid (31%) using 6-(pyridin-3-yloxy)-
pyridin-3-yl boronic acid 3 and 2-bromobenzaldehyde ac-
cording to general procedure 2. Mp 82 ꢁC. IR (KBr): 1692,
1591, 1571, 1447, 1426, 1418, 1306, 1221, 1154, 1029,
Acknowledgements
1
926, 849, 725, 683 cmꢀ1. H NMR (400 MHz, CDCl3):
ꢀ
The authors thank Laboratoires Servier, Conseil Regional
d¼9.94 (s, 1H), 8.50 (d, J¼2.4, 1H), 8.42 (d, J¼4.6, 1H),
ꢀ
de Basse-Normandie and FEDER (Fonds Europeens de
Developpement Economique Regional) for their financial
8.08 (d, J¼2.7, 1H), 7.97 (dd, J¼8.3, 2.4, 1H), 7.70 (dd,
ꢀ
ꢀ
3
J¼8.3, 2.7, 1H), 7.67 (part A of systAB, JAB¼7.5, J¼7.8,
support.
3
1.5, 1H), 7.54 (part A of systAB, JAB¼8.3, J¼2.7, 1.2,
1H), 7.47–7.50 (m, 2H), 7.35 (dd, J¼7.8, 2.1, 1H), 7.05 (d,
J¼8.3, 1H). 13C NMR (100 MHz, CDCl3): d¼191.3, 162.8,
150.3, 147.6, 145.2, 143.6, 141.1, 138.2, 134.3, 133.8,
131.0, 129.3, 129.0, 128.8, 128.6, 124.1, 111.3. Anal. Calcd
for C17H12N2O2: C, 73.90; H, 4.38; N, 10.14. Found: C,
73.73; H, 4.10; N, 10.07.
References and notes
1. For recent reviews on nAChR ligands, see: (a) Romanelli,
M. N.; Gualtieri, F. Med. Res. Rev. 2003, 23, 393–426; (b)
Bunnelle, W. H.; Dart, M. J.; Schrimpf, M. R. Curr. Top.
€
Med. Chem. 2004, 4, 299–334; (c) Jensen, A. A.; Frolund,
3.3.6. 2-[6-(5-Chloropyridin-3-yloxy)pyridin-3-yl]benz-
aldehyde (11). 2-[6-(5-Chloropyridin-3-yloxy)pyridin-3-yl]-
benzaldehyde was prepared as a yellow solid (90%) using
6-(5-chloropyridin-3-yloxy)pyridin-3-yl boronic acid 4 and
2-bromobenzaldehyde according to general procedure 2.
Mp 130 ꢁC. IR (KBr): 1695, 1599, 1573, 1469, 1427, 1304,
B.; Liljefors, T.; Krogsgaard-Larsen, P. J. Med. Chem. 2005,
48, 4705–4745.
2. (a) Lee, J. WO0010997, 2000; (b) Lee, J.; Davis, C. B.; Rivero,
R. A.; Reitz, A. B.; Shank, R. P. Bioorg. Med. Chem. Lett. 2000,
10, 1063–1066.
3. (a) Holladay, M. W.; Wasicak, J. T.; Lin, N. H.; He, Y.; Ryther,
K. B.; Bannon, A. W.; Buckley, M. J.; Kim, D. J.; Decker,
M. W.; Anderson, D. J.; Campbell, J. E.; Kuntzweiler, T. A.;
Donnelly-Roberts, D.; Piattoni-Kaplan, M.; Briggs, C. A.;
Williams, S.; Arneric, S. P. J. Med. Chem. 1998, 41, 407–
412; (b) Donnelly-Roberts, D. L.; Puttfarcken, P. S.;
Kuntzweiler, T. A.; Briggs, C. A.; Anderson, D. J.; Campbell,
J. E.; Piattoni-Kaplan, M.; McKenna, D. G.; Wasicak, J. T.;
Holladay, M. W.; Williams, M.; Arneric, S. P. J. Pharmacol.
Exp. Ther. 1998, 285, 777–786.
1272, 1249, 1020, 921, 848, 762, 685 cmꢀ1 1H NMR
.
(400 MHz, CDCl3): d¼10.02 (s, 1H), 8.47 (d, J¼2.2, 1H),
8.46 (d, J¼2.2, 1H), 8.18 (d, J¼2.2, 1H), 8.06 (dd, J¼7.8,
2.2, 1H), 7.79 (dd, J¼7.8, 1.9, 1H), 7.66 (t, J¼2.2, 1H),
3
7.62 (part B of systAB, JAB¼7.3, J¼7.8, 1.0, 1H), 7.64
3
(part A of systAB, JAB¼7.3, J¼7.9, 1.9, 1H), 7.41 (dd,
J¼7.9, 1.0, 1H), 7.14 (d, J¼7.8, 1H). 13C NMR (100 MHz,
CDCl3): d¼191.2, 162.1, 147.4, 144.8, 144.6, 141.4, 141.3,
140.8, 138.4, 134.0, 133.7, 131.8, 129.8, 129.1, 128.9,
128.6, 111.4. Anal. Calcd for C17H11ClN2O2: C, 65.71; H,
3.57; N, 9.01. Found: C, 65.49; H, 3.35; N, 8.89.
4. Voisin, A. S.; Bouillon, A.; Lancelot, J.-C.; Lesnard, A.; Rault,
R. Tetrahedron 2006, 62, 6000–6005.