Month 2017
Synthesis of Indeno-Fused Pyrido[2,3-d]pyrimidines
3
160.0 (2C═O), 162.1 (Ar), 168.9 (N═C─N), 188.6 (C═O).
MS (EI, 70 eV): m/z (%) = 387 (61) [M + 1]+, 386 (75)
[M]+, 268 (37), 302 (30), 294 (52), 273 (78), 246 (64),
232 (65), 218 (57), 193 (100), 137 (45), 130 (47), 109
(54), 102 (63), 75 (48), 44 (30). Anal. Calcd (%) for
C23H15FN2O3: C, 71.50; H, 3.91; N, 7.25. Found C,
71.8; H, 4.1; N, 7.1.
3JHH = 6.6 Hz, CHind), 7.67 (2H, d, JHH = 7.2 Hz, ArH),
7.98 (1H, d, JHH = 7.2 Hz, CHind).
3
5-(4-Methoxy-phenyl)-1,3-dimethyl-5,11-dihydro-1H-indeno
[20,10:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4k). Yellow
1
powder: mp 266–268°C, 0.290 g, yield 75%. H NMR
(300 MHz, CDCl3): δ 3.36 (3H, s, CH3), 3.89 (3H, s,
OMe), 3.90 (3H, s, CH3), 7.04 (2H, d, JHH = 8.5 Hz,
3
3
ArH), 7.20 (2H, d, JHH = 8.5 Hz, ArH), 7.54 (1H, d,
5-(4-Hydroxy-phenyl)-1,3-dimethyl-5,11-dihydro-1H-indeno
3JHH = 7.2 Hz, CHind), 7.64–7.68 (2H,m, CHind), 7.95
[20,10:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4f).
Yellow
3
(1H, d, JHH = 7.5 Hz, CHind).
powder: mp 368–369°C, 0.228 g, yield 58%. IR (KBr):
(ῡmax /cmꢀ1): 3379, 3048, 2956, 1710, 1660, 1571,
1506, 1367, 1277, 1207 749. 1H NMR (300 MHz,
REFERENCES AND NOTES
CDCl3): δ 3.37 (3H, s, CH3), 3.90 (3H, s, CH3), 6.95
3
(2H, d, JHH
=
8.4 Hz, ArH), 7.15 (2H, d,
[1] Kumaravel, K.; Vasuki, G. Curr Org Chem 2009, 13, 1820.
[2] Noyori, R. Chem Commun 2005, 14, 1807.
[3] Talaviya, S.; Majmudar, F. J Med Sci 2012, 1, 7.
[4] Khurana, J. M.; Chaudhary, A.; Nand, B.; Lumb, A. Tetrahe-
dron Lett 2012, 53, 3018.
[5] Rosowsky, A.; Mota, C. E.; Queener, S. F. J Heterocyclic
Chem 1995, 32, 335.
[6] Nargund, L. V. G.; Reddy, Y. S. R.; Jose, R. Indian Drugs
1991, 29, 45.
[7] Thompson, A. M.; Bridges, A. J.; Fry, D. W.; Kraker, A. J.;
Denny, W. A. J Med Chem 1995, 38, 3780.
[8] Donkor, I. O.; Klien, C. L.; Liang, L.; Zhu, N.; Bradley, E.;
Clark, A. M. J. J Pharm Sci 1995, 84, 661.
3JHH = 8.4 Hz, ArH), 7.65–7.72 (2H, m, CHind), 7.90
3
(1H, d, JHH
= 7.9 Hz, CHind), 7.98 (1H, d,
3JHH = 8.7 Hz, CHind). 13C NMR (75 MHz, CDCl3): δ
28.4 (CH3), 30.5 (CH3), 107.1 (C─C═N), 114.7 (Ar),
121.1 (Cind), 121.7 (CHind), 123.5 (CHind), 124.5
(CHind), 128.8 (Ar), 132.6 (Cipso Ar), 134.8 (CHind),
136.4 (Cind), 140.5 (Cind), 150.9 (C-Ar), 153.5 (C3ind),
155.5, 160.0 (2C═O), 157.6 (Ar), 168.4 (N═C─N),
188.6 (C═O). MS (EI, 70 eV): m/z (%) = 384 (100),
271 (12), 192 (10). Anal. Calcd (%) for C23H16N2O4:
C, 71.87; H, 4.20; N, 7.29. Found C, 71.7; H, 4.3;
N, 7.1.
[9]
Pastor, A.; Alajarin, R.; Vaquero, J. J.; Alvarez-Builla, J.;
Faude Casa-Juana, M.; Alvarez-Builla, J.; Sunkel, C.; Priego, J. G.;
Fonseca, I.; Sanz-Aparicio, J. Tetrahedron 1994, 50, 8085.
[10] Kolla, V. E.; D-Eyanov, A. B.; Nazmedinov, F. Y.; Kashina, Z.
N.; Rovosekova, L. P. Khim Farm Zh 1991, 27, 29.
[11] Satti, N. K.; Suri, K. A.; Sun, O. P.; Kapil, A. Indian J Chem
Sec B 1993, 32, 978.
[12] Bystryakove, I. D.; Burova, I. A.; Chelysheva, G. M.;
Zhilinkova, S. V.; Smirnova, N. M.; Safonova, T. S.; Safonova, T. S. Khim
Farm Zh 1991, 25, 31.
[13] Deyanov, A. B.; Niyazov, R. K.; Nazmetdinov, F. Y.;
Syropyatov, B. Y.; Kolla, V. E.; Konshin, M. E. Khim Farm Zh 1991,
25, 26.
[14] Monge, A.; Martinez-Merino, V.; Sanmartin, C.; Fernamdez,
F. J.; Ochoa, M. C.; Berllver, C.; Artigas, P.; Fernandez-Alvarez, E. Eur
J Med Chem 1989, 24, 209.
[15] Saladowwska, H.; Bartoszko-Malik, A.; Zawisza, T. Farmacol
1990, 45, 101.
[16] Agarwal, A.; Chauhan, P. M. S. Tetrahedron Lett 2005, 46,
1345.
[17] Finn, R. S.; Dering, J.; Conklin, D.; Kalous, O.; Cohen, D.
J.; Desai, A. J.; Ginther, C.; Atefi, M. Breast Cancer Res 2009, 11,
77.
[18] Rocca, A.; Farolfi, A.; Bravaccini, S.; Schirone, A.; Amadori,
D. Expert Opin Pharmacother 2014, 15, 407.
5-(4-Chloro-phenyl)-1,3-dimethyl-5,11-dihydro-1H-indeno
[20,10:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4g).
powder: mp 309–311°C, 0.320 g, yield 82%. H NMR
Yellow
1
(300 MHz, CDCl3): δ 3.36 (3H, s, CH3), 3.91 (3H, s,
3
CH3), 7.18 (2H, d, JHH = 8.1 Hz, ArH), 7.47 (2H, d,
3
3JHH = 8.1 Hz, ArH), 7.55 (1H, d, JHH = 6.9 Hz, CHind),
3
7.65–7.70 (2H, m, CHind), 7.98 (1H, d, JHH = 7.2 Hz,
CHind).
5-(4-Bromo-phenyl)-1,3-dimethyl-5,11-dihydro-1H-indeno
[20,10:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4h).
Yellow
1
powder: mp 299–301°C, 0.366 g, yield 84%. H NMR
(300 MHz, CDCl3): δ 3.36 (3H, s, CH3), 3.90 (3H, s,
3
CH3), 7.11 (2H, d, JHH = 8.4 Hz, ArH), 7.57 (1H, d,
3
3JHH = 7.5 Hz, CHind), 7.62 (2H, d, JHH = 8.4 Hz, ArH),
3
7.63–7.70 (2H, m, CHind), 7.98 (1H, d, JHH = 7.5 Hz,
CHind).
5-(4-Nitro-phenyl)-1,3-dimethyl-5,11-dihydro-1H-indeno
[20,10:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione
(4i).
[19] Tinkelman, D. G.; Berkowitz, R. B. Ann Allergy 1991, 66,
162.
Orange powder: mp 261–263°C, 0.386 g, yield 96%.
[20] Iacovino, R.; Rapuano, F.; Caso, J. V.; Russo, A.; Lavorgna,
M.; Russo, C.; Isernia, C. Int J Mol Sci 2013, 14, 13022.
[21] Atkinson, A. J. Jr.; Huang, S. M.; Lertora, J. J.; Markey, S. P.
Principles of Clinical Pharmacology; Academic Press, 2012.
[22] Dina, R.; Jafari, M. Am J Health Syst Pharm 2000, 57,
1231.
[23] Evdokimov, N. M.; Van Slambrouck, S.; Heffeter, P.; Tu, L.;
Le Calve, B.; Lamoral-Theys, D.; Steelant, W. F. J Med Chem 2011, 54,
2012.
[24] Ji, S. J.; Ni, S. N.; Yang, F.; Shi, J. W.; Dou, G. L.; Li, X. Y.;
Shi, D. Q. J Heterocycl Chem 2008, 45, 693.
[25] Verma, G. K.; Raghuvanshi, K.; Kumar, R.; Singh, M. S. Tet-
rahedron Lett 2012, 53, 399.
1H NMR (300 MHz, CDCl3): δ 3.35 (3H, s, CH3),
3
3.92 (3H, s, CH3), 7.42 (2H, d, JHH = 8.7 Hz, ArH),
3
7.57 (1H, d, JHH = 7.2 Hz, CHind), 7.66–7.70 (2H, m,
3
CHind), 7.99(1H, d, JHH = 7.5 Hz, CHind), 8.37 (2H,
3
d, JHH = 8.7 Hz, ArH).
5-(4-Fluoro-phenyl)-1,3-dimethyl-5,11-dihydro-1H-indeno
[20,10:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4j).
Yellow
1
powder: mp 286–288°C, 0.258 g, yield 69%. H NMR
(300 MHz, CDCl3): δ 3.36 (3H, s, CH3), 3.91 (3H, s,
CH3), 7.15–7.26 (4H, m, ArH, CHind), 7.55 (1H, d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet