B. Singh et al. / Tetrahedron 67 (2011) 2441e2446
2445
CDCl3) 2.58 (3H, s), 3.14 (3H, s), 4.49 (2H, s), 7.04e7.09 (2H, m),
7.34e7.38 (2H, m), 7.45 (1H, s); HRMS (EI): m/z [MþH]þ found:
236.1188. C15H14N3 requires 236.1188.
m); dC (75 MHz, CDCl3) 52.0, 52.4, 117.3, 122.8, 124.0, 125.9, 126.0,
127.9, 130.6, 133.3, 135.5, 148.8, 154.7, 165.1; HRMS (EI): m/z
[MþH]þ found: 256.1082. C14H14N3O2 requires 256.1086.
4.2.9. 9-Ethyl-1-methyl-1,2-dihydro-benzo[b][1,8] naphthyridine-3-
4.2.17. 1-Phenylamino-1,2-dihydro-benzo[b][1,8]naphthyridine-3-
carbonitrile (4i). Light brown solid; yield: 88%; mp 123 ꢀC; Rf (5%
carboxylic acid methyl ester (4x). Light brown solid; yield: 94%; mp
EtOAc/Hexane) 0.30; IR (KBr): 2927, 2196, 1617 cmꢂ1
;
dH (300 MHz,
75 ꢀC; Rf (10% EtOAc/Hexane) 0.30; IR (KBr): 3295, 1719, 1246 cmꢂ1
;
CDCl3) 1.32 (3H, t, J 7.5 Hz), 3.04 (2H, q, J 7.5 Hz), 3.14 (3H, s), 4.49
(2H, s), 7.09e7.12 (2H, m), 7.34e7.38 (2H, m), 7.45 (1H, s); dC
(75 MHz, CDCl3) 14.4, 24.6, 35.0, 51.7, 105.9, 115.4, 122.7, 123.3,
125.9, 129.7, 131.0, 136.1, 139.2, 140.2, 147.5, 153.4; HRMS (EI): m/z
[MþH]þ found: 250.1343. C16H16N3 requires 250.1344.
dH (300 MHz, CDCl3) 3.84 (3H, s), 4.75 (2H, s), 6.82e7.02 (5H, m, 1H
D2O Exchangeable), 7.34e7.62 (7H, m); dC (75 MHz, CDCl3) 51.2,
52.0, 113.9, 117.3, 119.3, 120.9, 122.7, 123.3, 127.0, 128.6, 129.2, 130.5,
130.9, 133.4, 136.0, 141.0, 153.8, 165.0; HRMS (EI): m/z [MþH]þ
found: 332.1396. C20H18N3O2 requires 332.1399.
4.2.10. 7-Bromo-1-methyl-1,2-dihydro-benzo[b][1,8]naphthyridine-
4.3. General procedure for the synthesis of 4-cyano-acridine-
2-carboxylic acid methyl ester (5)
3-carbonitrile (4j). Light brown solid; yield: 81%; mp 124 ꢀC; Rf (5%
EtOAc/Hexane) 0.32; IR (KBr): 2925, 2206 cmꢂ1
; dH (300 MHz,
CDCl3) 3.13 (3H, s), 4.50 (2H, s), 7.06 (1H, s), 7.36e7.62 (4H, m); HRMS
To a solution of BH acetate (0.25 mmol) and DMF (4.0 mL)
were added malanonitrile (0.37 mmol) and K2CO3 (0.37 mmol).
The reaction mixture was continually stirred at room temperature
for 5 min. After completion of the reaction (as monitored by TLC),
the reaction mixture was allowed to pour into chilled water and
the precipitate was filtered out. The crude product was purified
via column chromatography using silica gel column chromatog-
raphy employing hexaneeEtOAc (70:30, v/v) as eluent to give
pure 5.
(EI): m/z [MþH]þ found: 300.0134. C14H11N3Br requires 300.0136.
4.2.11. 1,8-Dimethyl-1,2-dihydro-benzo[b][1,8]naphthyridine-3-car-
boxylic acid methyl ester (4k). Light brown solid; yield: 90%; mp
135 ꢀC; Rf (5% EtOAc/Hexane) 0.33; IR (KBr): 2928, 1625, 1237 cmꢂ1
;
dH (300 MHz, CDCl3) 2.43 (3H, s), 3.15 (3H, s), 3.82 (3H, s), 4.53 (2H,
s), 6.93e6.96 (1H, d, J 7.2 Hz), 7.34e7.37 (3H, m), 7.43 (1H, s); HRMS
(EI): m/z [MþH]þ found: 269.1296. C16H17N2O2 requires 269.1290.
4.2.12. 1-Ethyl-1,2-dihydro-benzo[b][1,8]naphthyridine-3-carboxylic
4.3.1. 4-Cyano-acridine-2-carboxylic acid methyl ester (5a). Yellow
solid; yield: 95%; mp 145 ꢀC; Rf (20% EtOAc/Hexane) 0.40; IR (KBr):
acid methyl ester (4l). Yellow solid; yield: 92%; mp 190 ꢀC; Rf (10%
EtOAc/Hexane) 0.30; IR (KBr): 2926, 1655, 1256 cmꢂ1
; dH (300 MHz,
2201, 1615, 1022 cmꢂ1
; dH (300 MHz, CDCl3) 4.06 (3H, s), 7.69 (1H, t,
CDCl3) 1.25 (3H, t, J 6.6 Hz), 3.72 (2H, q, J 6.9 Hz), 3.83 (3H, s), 4.57
(2H, s), 7.09 (1H, t, J 6.9 Hz), 7.26e7.54 (5H, m); HRMS (EI): m/z
[MþH]þ found: 269.1292. C16H17N2O2 requires 269.1290.
J 7.2 Hz), 7.96 (1H, t, J 7.2 Hz), 8.09 (1H, d, J 8.4 Hz), 8.42 (1H, d, J
8.4 Hz), 8.79 (1H, s), 9.00 (1H, s), 9.01 (1H, s); dC (75 MHz, CDCl3)
29.7, 52.9, 113.8, 116.8, 124.8, 126.3, 127.6, 128.4, 130.2, 132.9, 136.1,
137.6, 139.0, 147.6, 151.1, 164.9; HRMS (EI): m/z [MþH]þ found:
263.0823. C16H11N2O2 requires 263.0820.
4.2.13. 1-(4-Methoxy-benzyl)-1,2-dihydro-benzo[b][1,8]naphthyr-
idine-3-carboxylic acid methyl ester (4o). Yellow solid; yield: 95%;
mp 130 ꢀC; Rf (5% EtOAc/Hexane) 0.50; IR (KBr): 2934, 1692,
Acknowledgements
1248 cmꢂ1
; dH (300 MHz, CDCl3) 3.78 (3H, s), 3.79 (3H, s), 4.46 (2H,
s), 4.90 (2H, s), 6.84e6.87 (2H, m), 7.13 (1H, t, J 7.8 Hz), 7.37e7.58
(7H, m); dC (75 MHz, CDCl3) 48.3, 49.7, 51.9, 55.2, 113.9, 116.9, 122.3,
123.8, 124.7, 126.2, 127.7, 129.4, 129.8, 130.4, 133.8, 135.9, 149.4,
153.7, 158.9, 165.3; HRMS (EI): m/z [MþH]þ found: 361.1551.
C22H21N2O3 requires 361.1552.
We thank CSIR (New Delhi) and UGC (New Delhi) for funding.
A.C. is thankful to UGC for awarding DSK Postdoc. fellowship, B.S. is
thankful to CSIR, New Delhi, for the award of Senior Research
Fellowship. We are also thankful to Prof. Y. D. Vankar and Prof.
Sandeep Verma, Department Of Chemistry, IIT Kanpur for use of the
HRMS facility.
4.2.14. 1-Isopropyl-1,2-dihydro-benzo[b][1,8]naphthyridine-3-car-
boxylic acid methyl ester (4p). Yellow solid; yield: 91%; mp 135 ꢀC;
Supplementary data
Rf (5% EtOAc/Hexane) 0.65; IR (KBr): 1709,1249 cmꢂ1
; dH (300 MHz,
CDCl3) 1.24 (6H, d, J 6.9 Hz), 3.84 (3H, s), 4.46 (2H, s), 5.35e5.47 (1H,
m), 7.09 (1H, t, J 7.5 Hz), 7.36e7.53 (5H, m); dC (75 MHz, CDCl3) 10.3,
41.3, 43.9, 51.9, 117.5, 122.1, 123.3, 124.8, 126.1, 127.6, 130.2, 133.8,
135.7, 149.5, 153.6, 165.5 cmꢂ1; HRMS (EI): m/z [MþH]þ found:
283.1447. C17H19N2O2 requires 283.1446.
Supplementary data related to this article can be found online at
InChIKeys of the most important compounds described in this
article.
References and notes
4.2.15. 1-(4-Nitro-phenyl)-1,2-dihydro-benzo[b][1,8]naphthyridine-
3-carboxylic acid methyl ester (4u). Brown solid; yield: 86%; mp
1. (a) Sekar, M.; Rajendra Prasad, K. J. J. Nat. Prod. 1998, 61, 294; (b) Puricelli, L.;
Innocenti, G.; Delle Monache, G.; Caniato, R.; Filippini, R.; Cappelletti, E. M. Nat.
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McPhail, A. T.; Sim, G. A. J. Am. Chem. Soc. 1966, 88, 3888; (d) Wall, M. E.; Wani,
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Tetrahedron 2006, 62, 2313.
135 ꢀC; Rf (10% EtOAc/Hexane) 0.24; IR (KBr): 2922, 1715 cmꢂ1
; dH
(300 MHz, CDCl3) 3.87 (3H, s), 4.91 (2H, s), 7.56e7.67 (6H, m), 7.83
(2H, s), 8.26e8.29 (2H, m); dC (75 MHz, CDCl3) 49.3, 52.3, 123.0,
124.2, 124.6, 125.2, 125.7, 127.2, 127.6, 127.7, 127.8, 127.9, 128.0,
130.9, 133.2, 135.8, 136.8, 164.8; HRMS (EI): m/z [MþH]þ found:
362.1140. C20H16N3O4 requires 362.1141.
3. (a) Chen, Q. P.; Leslie, W. D.; Bruce, C. B.; William, A. D. J. Med. Chem. 1994, 37,
593; (b) Wissner, A.; Hamann, P.R.; Yamashita, A. WO 0066583, 2000; CAN 133,
350203; (c) Mabire, D.; Coupa, S.; Adelinet, C.; Poncelet, A.; Simonnet, Y.; Venet,
M.; Wouters, R.; Lesage, A. S. J.; Beijsterveldt, L. V.; Bischoff, F. J. Med. Chem.
2005, 48, 2134.
4.2.16. 1-Amino-1,2-dihydro-benzo[b][1,8]naphthyridine-3-carbox-
ylic acid methyl ester (4w). Yellow solid; yield: 91%; mp 96 ꢀC; Rf
(15% EtOAc/Hexane) 0.40; IR (KBr): 3512, 1712, 1248 cmꢂ1
; dH
(300 MHz, CDCl3) 3.83 (3H, s), 4.61 (2H, br s, D2O exchangeable NH2
proton), 4.71 (2H, s), 7.16 (1H, t, J 7.5 Hz), 7.39 (1H, s), 7.51e7.59 (4H,
4. (a) Naik, T. R. R.; Naik, H. S. B.; Raghavendra, M.; Naik, S. G. K. Arkivoc 2006, xv,
84; (b) Wang, Y. D.; Diane, H.; Boschelli, D. H.; Steven, J.; Erick, H. Tetrahedron