1
444
A Simple Synthesis of Aminopyridines: Use of Amides as Amine Source
J. Braz. Chem. Soc.
3
2
2
-(Dimethylamino)nicotinonitrile (3f)
Acknowledgments
1
Colorless liquid; H NMR (DMSO-d , 400 MHz) d 8.34
6
(
(
2
dd, 1H, J 4.8; 1.8 Hz), 7.97 (dd, 1H, J 7.6; 1.8 Hz), 6.76
A. K. thanks the management of Matrix Laboratories
Ltd for continuous support and encouragement.
-1
dd, 1H, J 7.6; 4.8 Hz), 3.20 (s, 6H); IR (KBr) νmax/cm :
927, 2211, 1589, 1552, 1511, 1409, 1245, 960, 759; MS
CI method): 148 (M+1, 100%).
(
References
3
3
N,N-Dimethylpyridine-4-amine (3g)
1. Aicher, T. D.; Boyd, S. A.; Chicarelli, M. J.; Condroski, K. R.;
Hinklin, R. J.; Singh, A.; US Pat. 20090156603 2007.
2. Lawton, G. R.; Ranaivo, H. R.; Chico, L. K.; Ji, H.; Xue, F.;
Martásek, P.; Roman, L. J.; Watterson, D. M.; Silverman, R.
B.; Bioorg. Med. Chem. 2009, 17, 2371.
o
1
White solid; mp 109-111 C; H NMR (DMSO-d ,
6
4
5
1
00 MHz) d 8.10 (dd, 2H, J 5.2; 1.5 Hz), 6.58 (dd, 2H, J
.1; 1.3 Hz), 2.94 (s, 6H); IR (KBr) νmax/cm : 2902, 2825,
604, 1536, 1445, 1377, 1223, 1104, 1068, 988, 808, 749;
-
1
MS (CI method): 145 (M+Na, 100%).
3. For anticancer agents, see: Temple, C. Jr.; Rose, J. D.; Comber,
R. N.; Rener, G. A.; J. Med. Chem. 1987, 30, 1746; Temple,
C., Jr.; Smith, B. H.; Elliott, R. D.; Montgomery, J. A.; J. Med.
Chem. 1973, 16, 292.
34
N-Methyl-5-nitropyridin-2-amine (3h)
o
1
Yellow solid; mp 180-182.3 C; H NMR (DMSO-d ,
6
4
00 MHz) d 8.92 (s, 1H), 8.09 (m, 2H), 6.53 (d, 1H, J 9.2
4. For kinase inhibitors, see: Audrey, D.; Michelle, L.; Paul,
L.; Peter, M.; Bin, W.; Tao, W.; Dingwei, Y.; World pat. WO
2006/082392A1 2006.
-
1
Hz), 2.90 (bs, 3H); IR (KBr) νmax/cm : 3370, 1619, 1600,
542, 1481, 1463, 1419, 1394, 1324, 1265, 831; MS (CI
method): 154 (M+1, 100%).
1
5. For selective antihistamine (H ) agents, see: Janssens, F.;
1
Torremans, J.; Janssen, M.; Stokbroekx, R. A.; Luyckx, M.;
Janssen, P. A. J.; J. Med. Chem. 1985, 28, 1943.
3
5
N-Methyl-5-(trifluoromethyl)pyridine-2-amine (3i)
o
1
Off-white solid; mp 50-53 C; H NMR (DMSO-d ,
00 MHz) d 8.35 (s, 1H), 7.66 (d, 1H, J 7.2 Hz), 7.32 (bs,
H), 6.60 (d, 1H, J 8.8 Hz), 2.86 (d, 3H, J 4.8 Hz); IR (KBr)
6. For anti-inflammatory agents, see: Gipf-Oberfrick, G. B.;
Bennwil, J. D. K.; Hoelstein, J. F.; Hegenheim, R. H.;
Arlesheim, P. W. M.; Efringen-Kirchen, B. W.; Biel-Benken,
J. M. W.; US Pat. 2006/0217388A1 2006.
6
4
1
-
1
νmax/cm : 3276, 1625, 1540, 1394, 1328, 1106, 939, 825;
MS (CI method): 177 (M+1, 100%).
7. For Angiotensin II receptor antagonists, see: Mantlo, N. B.;
Chakravarty, P. K.; Ondeyka, D. L.; Siegl, P. K. S.; Chang, R.
S.; Lotti, V. J.; Faust, K. A.; Schorn, T. W.; Chen, T. B.; J. Med.
Chem. 1991,34, 2919.
3
6
2
-(Methylamino)nicotinonitrile (3j)
o
1
Yellow solid; mp 86.3-88.4 C; H NMR (DMSO-d ,
6
3
00 MHz) d 8.28 (dd, 1H, J 4.9 & 1.9 Hz), 7.87 (dd, 1H,
8. For anti-diabetic agents, see: Oguchi, M.;Wada, K.; Honma, H.;
Tanaka, A.; Kaneko, T.; Sakakibara, S.; Ohsumi, J.; Serizawa,
N.; Fujiwara, T.; Horikoshi, H.; Fujita, T.; J. Med. Chem. 2000,
43, 3052.
J 7.6; 1.9 Hz), 7.06 (bs, 1H), 6.62 (dd, 1H, J 7.6; 4.9 Hz),
-
1
2
1
8
.85 (d, 3H, J 4.6 Hz); IR (KBr) νmax/cm : 3378, 2220,
599, 1583, 1527, 1471, 1400, 1347, 1276, 1256, 1157,
61, 760; MS (CI method): 134 (M+1, 100%).
9. For thromboxane A receptor antagonists, see: Nicolai, E.;
2
Claude, S.; Teulon, J. M.; J. Heterocycl. Chem. 1994, 31, 73.
10. Brunel, S.; Montginoul, C.; Torreilles, E.; Giral, L.;
J. Heterocycl. Chem. 1980, 17, 235.
3
7
5
-Nitropyridin-2-amine (3k)
o
1
Pale yellow solid; mp 182-185 C; H NMR (DMSO-d ,
6
3
2
00 MHz) d 8.83 (d, 1H, J 2.8 Hz), 8.11 (dd, 1H, J 9.2;
.8 Hz), 7.51 (bs, 2H), 6.49 (d, 1H, J 9.2 Hz); IR (KBr)
11. Blache, Y.; Gueiffier, A.; Chavignon, O.; Teulade, J.
C.; Milhavet, J. C.; Viols, H.; Chapat, J. P.; Daupin, G.;
J. Heterocycl. Chem. 1994, 31, 161.
-1
νmax/cm : 3495, 3366, 1648, 1633, 1593, 1571, 1495, 1473,
334, 1315, 1298, 1285, 1130, 842; MS (CI method): 140
M+1, 100%).
1
(
12. Khanna, I. K.; Weier, R. M.; Lentz, K. T.; Swenton, L.; Lakin,
D. C.; J. Org. Chem.1995, 60, 960.
1
3. Kim,Y. H.; Kim,Y. J.; Chang, S-Y.; Kim, B. T.; Heo, J-N.; Bull.
Korean Chem. Soc. 2007, 28, 777.
3
8
Pyridine-4-amine (3l)
o
1
White solid; mp 154-156 C; H NMR (DMSO-d ,
14. Munson, P. M.; Thomson, W. J.; Synth. Commun. 2004, 34,
759.
6
4
5
1
00 MHz) d 7.95 (dd, 2H, J 5.1; 1.4 Hz), 6.44 (dd, 2H, J
.1; 1.4 Hz), 5.96 (bs, 2H); IR (KBr) νmax/cm : 3436, 3301,
648, 1601, 1557, 1507, 1435, 1333, 1269, 1217, 991, 822;
-1
15. Lurthy, N. G.; Bergstrom, F. W.; Mosher, H. S.; J. Am. Chem.
Soc. 1949, 71, 1109.
MS (CI method): 117 (M+Na, 100%).
16. Pino, L. N.; Zehrung, W. S.; J. Am. Chem. Soc. 1955, 77, 3154.