142
A.M. Soliman et al. / European Journal of Medicinal Chemistry 47 (2012) 138e142
NH2); MS m/z (%): Mþ 214 (44.1), 198 (52.2), 167 (60.3), 105 (33.2),
67 (100); Anal.Calc. For C10H10N6 (214.23): C(56.07%) H(4.71%)
N(39.23%). Found: C(56.14%) H(4.08%) N(39.01%).
2.2.2.5. Barbaturic acid
ꢀ
3,4-dihydrobenzo [4,5]imidaꢀzo1[1,2-a]
[1,3,5]triazin-2-amine 12. Yield 88%, mp 340 ꢂC; IR: cm 3387,
3264, 3175 (NH2,3NH), 1688 (CO), 1679 (CO); 1H NMR:
d 10.24 (s,1H,
NH), 9.68 (s,2H, 2NH), 7.58e7.07 (m,4H, arom), 5.26 (br,2H, NH2),
2.2.1.6. (2Z)-4-Amino-2-(1,3-benzimidazol-2-ylimino)-2,5-dihydro-
3.24 (s,2H, CH2); 13C NMR:
d 53.50, 61.89, 104.00, 116.13, 122.23,
1H-imidazole-5-carbonitrile (7). Mp 330 ꢂC, yield 73%; IR: cmꢀ1
123.24, 124.20, 140.83, 157.95, 161.81, 170.33; MS m/z (%): Mþ 285
(27.47), 261 (31.1), 242 (100), 185(20.2), 77 (35.1); Anal.Calc. For
C12H11N7O2(285.26):C(50.53%) H(3.89%) N(34.37%). Found:
C(50.22%) H(3.77%) N(34.13%).
3381, 3288, 3176 (2NH,NH2), 2222(CN); 1H NMR:
d 10.05 (s,1H, NH),
7.75e7.04 (br,5H, arom þ NH), 06.19 (s,1H, NH), 5.23 (s,2H, NH2);
MS m/z (%): Mþ 240 (42.1), 198 (82.0), 172 (100), 148 (66.2), 105
(77.6); Anal.Calc. For C11H10N7 (240.25): C(55.22%) H(3.79%)
N(40.98%). Found: C(55.02%) H(3.59%) N(40.57%).
2.2.2.6. Camphor ꢀ 3,4-dihydrobenzo [4,5]imidazo[1,2-a][1,3,5]tri-
azin-2-amine 13. Yield 71%, mp ¼ 360 ꢂC; IR: cmꢀ1 3374, 3235, 3167
2.2.2. General procedure. 8e13
(NH, NH2); 13C NMR:
d 9.02, 22.77, 26.55, 30.18, 32.36, 35.27, 36.34,
A mixture of compound 1 (50 mmol) and (50 mmol) cyclo-
pentanone, cyclohexanon, thiazolidione, pyrazolone, barbituric
acid and camphor in ethanol and presence of a few drops of
hydrochloric acid as a catalyst was refluxed, solid products were
observed after 5 h. After cooling down, the solid crystalline prod-
ucts were filtered, washed and recrystalised from ethanol.
53.39, 80.45, 109.87, 116.36, 122.84, 123.45, 128.80, 140.77, 158.17,
161.98; MS m/z (%): Mþ 309 (28.55), 288 (67.24), 167 (56.9), 76
(100); Anal.Calc. For C19H23N5O (309.41): C(67.63%) H(6.87%)
N(20.76%). Found: C(67.35%) H(6.32%) N(20.01%).
References
2.2.2.1. Cyclopentane ꢀ 3,4-dihydrobenzo [4,5]imidazo[1,2-a][1,3,5]
triazin-2-amine 8. Yield 81%, mp ¼ 310 ꢂC; IR: cmꢀ13381, 3277, 3177
[1] (a) J.V. Greenhill, L. Lue, in: G.P. Ellis, D.K. Luscombe (Eds.), Progress in
Medicinal Chemistry, vol. 3, Elsevier, New York, 1993;
(NH2,NH); 1H NMR:
d 09.87 (s,1H, NH), 7.58e7.12 (m,4H, arom), 4.77
(b) M.R. Grimmett, in: A.R. Katrilzky, C. W.Rees, E.F. V.Sciven (Eds.),
Comprehensive Heterocyclic Chemistry, vol. 3, Pergamon, Oxford, 1996, pp.
77e220.
(br,2H, NH2), 2.08 (s,4H, 2CH2), 1.90 (s,4H, 2CH2); 13C NMR:
d 23.09,
36.74, 68.03, 110.63, 116.46, 122.68, 123.43,129.33, 141.30, 159.63,
160.44; MS m/z (%): Mþ 241 (38.1), 225 (66.5), 196 (34.2), 118 (88.1),
76 (100); Anal.Calc. For C13H15N5 (241.30): C(64.71%) H(6.27%)
N(29.02%). Found: C(64.44%) H(6.02%) N(28.94%).
[2] (a) R.C.F. Jones, J.R. Nichols, Tetrahedron Lett. 31 (1990) 1771e1774;
(b) M. Jung, E.A. Huang, Org. Lett. 2 (2000) 2659e2661.
[3] (a) R.C. F.Jones, I. Turner, K.J. Howard, Tetrahedron Lett. 34 (1993)
6329e6332;
(b) Y. Langlois, P.I.J. Dalko, Org. Chem. 63 (1998) 8107e8117.
[4] (a) T. Morimoto, K. Tachibana, K. Achiwa, Synlett. (1997) 783e785;
(b) A.J. Davinport, D.L. Davies, J. Fawcett, D.R.J. Russell, Chem. Soc. Perkin
Trans. 1 (2001) 1500;
(c) F. Menges, M. Neuburger, A. Pfaltz, Org. Lett. 4 (2002) 4713e4716.
[5] (Chapter 10)A.G. Gilman, L.S. Goodman (Eds.), The Pharmacological Basis of
Therapeutics, tenth ed.. Macmillan & Co., New York, 2001, pp. 215e268.
[6] J.V. Greenhill, P. Lue, Progress in Medicinal Chemistry. Elsevier Science, New
York, 1993, p. 203.
2.2.2.2. Cyclohexane ꢀ 3,4-dihydrobenzo [4,5]imidazo[1,2-a][1,3,5]
triazin-2-amine 9. Yield 82%, mp ¼ 285 ꢂC; IR: cmꢀ1 3384, 3269,
3177 (NH2,NH); 1H NMR:
d 10.02 (s,1H, NH), 7.58e7.11 (m,4H,
arom), 4.81 (br,2H, NH2), 1.77e1.48 (m,10H, 5CH2); 13C NMR:
d
21.91, 25.58, 36.04, 64.98, 110.55, 116.46, 122.68, 123.43, 129.01,
141.14, 159.68, 160.54; MS m/z (%): Mþ 255 (24.4), 239 (55.4), 167
(81. 1), 77 (100); Anal.Calc. For C14H17N5 (255.32): C(65.86%)
H(6.71%) N(27.43%). Found: C(65.20%) H(6.47%) N(27.05%).
[7] G.L. Bihan, F. Rondu, A.T. Pele, X. Wang, S. Lidy, E. Touboul, A. Lamouri, G. Dive,
J. Huet, B. Pfeiffer, P. Renard, B.L. Guardiola, D. Manechez, L. Penicaud,
A. Ktorza, J.J. Godfroid, J. Med. Chem. 42 (1999) 1587.
[8] F.H.S. Curd, W. Graham, F.L. Rose, J.Chem.Soc. 594 (1948).
[9] M. Negwer, OrganiceChemical Drugs and Their Synonyms. Wiley-VCH Verlag
GmbH, Weinheim, 2001.
[10] M. Jarman, H.M. Coleg, I.R. Judson, T.J. Thornton, D.E.V. Wilman, J.Med. Chem.
36 (1993) 4195e4200.
[11] J. Soudon, M. Berlion, C. Lucas, P. Haddad, F. Calvo, Cancer Chemo-
ther.Pharmacol. 36 (1995) 195e199.
[12] J.P. Tassin, J. Dubois, M. Hancoq, G. Atassi, Talanta 42 (1995) 747e752.
[13] M. Ono, N. Kawahara, D. Goto, Y. Wakabayashi, S. Ushiro, Cancer Res. 56
(1996) 1512.
[14] R. Menicagli, S. Samaritani, G. Signore, F. Vaglini, L.D. Via, J. Med.Chem. 47
(2004) 4649e4652.
[15] N. Baindur, N. Chadha, B.M. Brandt, D. Asgari, R.J. Patch, C. Schalk-HiHi,
T.E. Carver, I.P. Petrounia, C.A. Baumann, H. Ott, C. Manthey, B.A. Springer,
M.H. Player, J. Med. Chem. 48 (2005) 1717e1720.
[16] M. Ono, N. Kawahara, D. Goto, Y. Wakabayashi, S. Ushira, S. Yoshida, H. Izumi,
M. Kuwano, Y. Sato, Cancer Res. 56 (1996) 1512.
[17] S. Nozaki, M. Maeda, H. Truda, G.W. Sledze, Breast Cancer Res. Treat. 83 (2004)
195e199.
2.2.2.3. Thiazolidin-4-one ꢀ 3,4-dihydrobenzo [4,5]imidazo[1,2-a]
[1,3,5]triazin-2-amine 10. Yield 79%, mp 265 ꢂC; IR: cmꢀ1 3381,
3261, 3177 (NH2,2NH), 1688 (CO); 1H NMR:
d
10.15 (s,1H, NH),
7.60e7.10 (m,4H, arom), 6.83 (s,1H, NH), 4.80 (br,2H, NH2), 3.98
(s,2H, CH2); 13C NMR:
d 32.12, 83.44, 106.40, 117.81, 123.60, 125.62,
141.45, 163.22, 169.83, 174.12; MS m/z (%): Mþ 274(25.4), 258 (39.1),
198 (88.7), 105 (100); Anal.Calc. For C11H10N6OS (274.30): C(48.17%)
H(3.67%) N(30.64%) S(11.69%). Found: C(48.07%) H(3.32%)
N(30.18%) S(11.48%).
2.2.2.4. 3-Methyl-1-phenyl-1H-pyrazole ꢀ 3,4-dihydrobenzo [4,5]
imidazo[1,2-a][1,3,5]triazin-2-amine 11. Yield 74%, mp ¼ 282 ꢂC; IR:
cmꢀ1 3384, 3270, 3177 (NH2,NH); 1H NMR:
d 10.08 (s,1H, NH),
7.58e7.01 (m,9H, 2 arom), 4.61 (br,2H, NH2), 3.17 (s,2H, CH2), 2.24
[18] F.E. King, R.M. Acheson, P.C. Spensley, J. Chem. Soc. (1948) 1366e1371.
[19] E. Jawetz, J.L. Melnick, E.A. Adelberg, Review of Medical Microbiology. Lang
Medical Publication, Los Altos, California, 1974.
[20] J.R. Grayer, J.B. Harbone, Phytochemistry 37 (1994) 19e42.
[21] D.N. Muanza, B.W. Kim, K.L. Euler, L. Williams, Pharm. Biol. 32 (1994)
337e345.
(s,3H, 2CH3); 13C NMR:
d
16.43, 38.17, 86.46, 108.78, 116.24, 122.74,
122.50, 124.19, 124.78, 126.19, 126.80, 139.18, 142.80, 155.29, 155.93,
157.44; MS m/z (%): Mþ 331 (22.8), 316 (60. 2), 204 (44.5),119 (58.6),
77 (100); Anal.Calc. For C18H17N7 (331.38): C(65.24%) H(5.17%)
N(29.59%). Found: C(65.09%) H(5.01%) N(29.18%).
[22] O.N. Irobi, M. Moo-Young, W.A. Anderson, Pharm. Biol. 34 (1996) 87e90.