MHz, CDCl3, δ) ; 7.34 – 7.30 (m, 2H), 7.24 – 7.21 (m, 3H), 6.99
9. Fink, K. A.; Gurwitz, J.; Rakowski, W.; Guadagnoli, E.; Silliman,
A. R. J. Clin. Oncol. 2004, 22, 3309.
–
4
2
6.97 (m, 1H), 6.80 – 6.78 (m, 2H), 5.72 (s, 1H), 4.80 (s, 2H),
.74(s, 1H), 3.66 (t, j = 5.3 Hz, 2H), 3.61(t, j = 4.7Hz, 4H),
.60- 2.55 (m, 6H), 2.41 (s, 1H); 13C NMR (100 MHz, CDCl3,
1
0. Burstein, J. H.; Temin, S.; Anderson, H.; Buchholz, A. T.;
Davidson, E. N.; Gelmon, E. K.; Giordano, H. S.; Hudis, A. C.;
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δ) 170.1, 167.8, 164.5, 159.3, 152.9, 149.0, 144.5, 130.5, 129.0,
1
5
1
28.1, 127.4, 120.0, 119.4, 118.0, 109.2, 83.8, 60.4, 59.4, 57.9,
2.6, 44.2, 40.7, 26.1; FT-IR (KBr) : 3400, 3200, 2217, 1640,
542, 1100, 580 cm-1; LC-MS (ESI+): m/z calculated for
11. (a) Doshi, J. M.; Tian, D.; Xing, C. J. Med. Chem. 2006, 49,
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7
Wang, Y.; Zhao, J.; Crogan-Grundy, C.; Xu, L.; Lamothe, S.;
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C
27
H
30
N
7
O
2
[M+H]+: 484.2, found: 484.2.
2-amino-7-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-
methylpyrimidin-4-yl)oxy)-4-(4-nitrophenyl)-4H-chromene-3-
carbonitrile (17) : Yield: 90% as Light Yellow; 1H NMR (400
MHz, CDCl3, δ) ; 8.12 – 8.10 (m, 1H), 8.01 (s, 1H), 7.61 (d, J =
1
2. (a) Ahmed, N.; Dubuc, C.; Rousseau, J.; Be´nard, F; van Lier, J.
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7
6
3
6
1
1
4
1
.5 Hz, 1H), 7.51 (t, J = 7.7 Hz, 1H), 6.91 (d, J = 8.1 Hz, 1H),
.83 – 6.81 (m, 2H), 5.73 (s, 1H), 5.12 (s, 1H), 4.91 (s, 2H),
.65(t, J = 5.2 Hz, 2H), 3.60 (t, J = 4.9 Hz, 4H), 2.58- 2.54 (m,
H), 2.38 (s, 1H); 13C NMR (100 MHz, CDCl3, δ): 169.9,
67.8, 164.6, 159.5, 153.5, 149.0, 148.8, 146.6, 134.8, 130.3,
30.0, 123.0, 122.7, 117.7, 109.6, 84.0, 59.0, 59.2, 57.9, 52.6,
4.2, 40.6, 26.1; FT-IR (KBr) : 3400, 3200, 2217, 1640, 1542,
100, 580 cm-1; LC-MS (ESI+): m/z calculated for
1
1
3. Gao, M.; Miller, K. D.; Hutchins, G. D.; Zheng, Q-H.; Appl.
Radiat. Isot. 2010, 68, 110–116.
4. Hu, M. J.; Zhang, B.; Yang, H. K.; Liu, Y.; Chen, Y. R.; Ma, T.
Z.; Lu, L.; You, W.W.; Zhao, P.L. Chem. Biol. Drug Des. 2015,
C28H27N7O5 [M+H]+: 528.2 found: 528.2.
-amino-7-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2methyl-
pyrimidin-4-yl)oxy)-4-(p-tolyl)-4H-chromene-3-carbonitrile
8
6, 1491-1500; (b) Galmarini, M. C.; Jordheim, L.; Dumontet , C.
2
Expert. Rev. Anticancer Ther. 2003, 3, 717; (c) Xie, F.; Zhao, H.;
Zhao, L.; Lou, L.; Hu, Y., Bioorg. Med. Chem. Lett. 2009, 19,
275–278; (d) Schenone, S.; Bruno, O.; Bondavalli, F.; Ranise, A.;
Mosti, L.; Menozzi, G.; Fossa, P.; Donnini, S.; Santoro, A.; Ziche,
M.; Manetti, F.; Botta, M. Eur. J. Med. Chem. 2004, 39, 939–946;
1
(
19) : Yield: 94% as Pale yellow; H NMR (400 MHz, CDCl
3
,
δ);7.13- 7.12 (m, 3H), 7.05 – 7.03 (m, 1H), 6.85 – 6.83 (m, 1H),
6
3
6
1
1
4
1
.77 – 6.73 (m, 2H), 5.69 (s, 1H), 5.06 (s, 1H), 4.75 (s, 2H),
(
e) Kim, C. D.; Lee, R. Y.; Yang, B.; Shin, J. K.; Kim, J. D.;
.64 (t, J = 5.2 Hz, 2H), 3.59 (t, J = 4.4 Hz, 4H), 2.58- 2.53(m,
Chung, Y. B.; Yoo, H. K.; Eur. J. Med. Chem. 2003, 38, 525–532.
13
H), 2.40 (s, 1H), 2.39 (s, 1H); C NMR (100 MHz, CDCl3, δ)
70.1, 167.9, 164.6, 159.0, 152.8, 149.0, 141.5, 137.1, 130.5,
29.7, 127.9, 119.5, 118.0, 109.2, 83.7, 61.0, 59.4, 57.9, 52.5,
4.2, 40.3, 40.1, 26.1, 21.1; FT-IR (KBr) : 3400, 3200, 2217,
15. Weinberg, R. L.; Albom, S. M.; Angeles, S. T.; Husten, J.; Lisko,
G. J.; McHugh, J. R.; Milkiewicz, L. K.; Murthy, S.; Ott , R. G.;
Theroff, P. J.; Tripathy, R.; Underiner, L.T.; Zificsak, A. C.;
Dorsey, D. B. Bioorg. Med. Chem. Lett. 2011, 21, 164–167.
1
1
1
6. Boschi, D.; Tosco, P.; Chandra, N.; Chaurasia, S.; Fruttero, R.;
Griffin, R.; Wang, Z. L.; Gasco, A. Eur. J. Med. Chem. 2013, 68,
333–338.
7. Savall, M. B.; Chavez, F.; Tays, K.; Dunford, J. P.; Cowden, M.
J.; Hack, D. M.; Wolin, L. R.; Thurmond, L. R.; Edwards, P. J.; J.
Med. Chem. 2014, 57, 2429–2439.
8. Marchetti, F.; Cano, C.; Curtin, J. N.; Golding, T. B.; Griffin, J.
R.; Haggerty, K.; Newell, R. D.; Parsons, J. R.; Payne, L. S.;
Wang, Z. L.; Hardcastle, R. I. Org. Biomol. Chem. 2010, 8, 2397–
2407.
-1
+
640, 1542, 1100, 580 cm LC-MS (ESI ): m/z calculated for
+
28 30 6 3
C H N O [M+H] : 499.2 found: 499.1.
Acknowledgments
IP is thankful to UGC New Delhi (Grant No- 6405-13-044), for
fellowship. We sincerely thank Instrumentation center and
department of chemistry IITR for various facilities.
1
9. Arris, E. C.; Boyle, T. F.; Calvert, H. A.; Curtin, J. N.; Endicott,
A. J.; Garman, F. E.; Gibson, E. A.; Golding, T. B.; Grant, S.;
Griffin, J. R.; Jewsbury, P.; Johnson, N. L.; Lawrie, M. A.;
Newell, R. D.; Noble, E. M.; Sausville, A. E.; Schultz, R.; Yu , W.
J. Med. Chem. 2000, 43, 2797–2804.
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