T. A. Farghaly, M. A. Abdallah, and M. R. Abdel Aziz
Vol 000
7.25–8.10 (m, 19H, Ar―H), 8.79, 9.0 (2s, 3H, Pyrazole-
H); MS m/z (%): 783 (M+ + 1, 53), 782 (M+, 82), 763
(31), 727 (46), 718 (70), 606 (45), 559 (45), 488 (59),
309 (50), 276 (45), 227 (69), 191 (43) 77 (100). Anal.
Calcd for C46H34N14 (782.86): C, 70.57; H, 4.38; N,
25.05. Found: C, 70.38; H, 4.16; N, 24.91%.
the spectral data of the products 15 and 16 prepared are
depicted below.
3,4-Bis-(triazolo[1,5-a]pyrimidin-5-yl)-5-methyl-1-[4-(triazolo[1,5-
a]pyrimidin-5-yl)--phenyl]-pyrazole (15).
Dark yellow solid,
1
(75% yield), mp 190–192 °C. H NMR (DMSO-d6) δ 2.08
(s, 3H, CH3), 6.85–7.78 (m, 4H, Ar―H), 7.95 (d, J=4.5Hz,
3H, pyrimidine-H), 8.45 (d, J=4.5Hz, 3H, pyrimidine-H),
8.69, 8.78 (2s, 3H, triazole H). MS m/z (%) 513 (M+ +1,
15), 512 (M+, 87), 511 (42), 500 (14), 110 (46), 75 (100).
Anal. Calcd. For C25H16N14 (512.17) C, 58.59; H, 3.15; N,
38.26. Found C, 58.38; H, 3.04; N, 38.10%.
3,4-Bis-(3-oxo-1-phenyl-1H,3H-pyrazolo[3,4-d]pyridazin-6-yl)-
5-methyl-1-[4-(3-oxo-1-phenyl-1H,3H-pyrazolo[3,4-d]pyridazin-6-
yl)-phenyl]-pyrazole (9). Pale yellow crystal, (64% yield),
mp 286–288°C (EtOH/Dioxane); IR (KBr) νmax 3384 (NH),
1
1658 (C¼O); H NMR (DMSO-d6) δ 1.23 (s, 3H, CH3),
3,4-Bis-(pyrimido[1,2-a]benzimidazol-4-yl)-5-methyl-1-[4-(pyrimido
7.54–8.18 (m, 19H, Ar―H), 8.83 (s, 3H, pyrazolyl-H),
12.65 (1s, 3H, 3NH). MS m/z (%): 788 (M+, 3), 785 (10),
218 (25), 118 (11), 104 (15), 92 (45), 77 (100). Anal. Calcd
for C43H28N14O3 (788.77): C, 65.48; H, 3.58; N, 24.86.
Found: C, 65.24; H, 3.39; N, 24.68%.
[1,2-a]benzimidazol-4-yl)-phenyl]-pyrazole (16).
Brown
1
solid (78% yield), mp 118–120°C; H NMR (DMSO-d6)
δ 1.90 (s, 3H, CH3), 6.17–7.11 (m, 16H, Ar―H), 7.42
(d, J = 4.5 Hz, 3H, pyrimidine-H), 7.43 (d, J = 4.5 Hz, 3H,
pyrimidine-H). MS m/z (%) 659 (M+, 15), 658 (34), 186
(25), 146 (13), 105 (65), 76 (48). Anal. Calcd. for
C40H25N11 (659.70): C, 72.83; H, 3.82; N, 23.36. Found:
C, C, 72.83; H, 3.82; N, 23.36%.
Reaction of enaminone
compounds.
4
with active methylene
General method—To a solution of 4
(0.90 g, 2mmole) in glacial acetic acid in the presence of
ammonium acetate (0.5 g), was added ethyl acetoacetate
(4 mmole). The reaction mixture was heated under reflux
for 25h. The reaction was followed by TLC. The reaction
mixture poured into cold water, the solid product were
filtered off and crystallized from ethanol to give
compound 14a. When the above method was repeated
using ethyl benzoylacetate in lieu ethyl acetoacetate the
respective product 14b was obtained. The products 14a,b
prepared are listed below together with their physical
constants.
Reaction of enaminones with hydrazine hydrate.
A
mixture of enaminone 4 (2.25 g, 5 mmol) and hydrazine
hydrate (5mL) in absolute ethanol was stirred at reflux
for 10h and cooled. The solid formed was separated by
filtration and crystallized from ethanol/dioxane mixture to
give compound 17 as brown solid, (83% yield), mp
1
208–210 °C; IR (KBr) νmax 3312, 3251 (NH) cmꢀ1; H
NMR (DMSO-d6) δ 2.48 (s, 3H, CH3), 7.12 (d, J = 8 Hz,
2H, Ar―H), 7.76 (d, J = 8Hz, 2H, Ar―H), 7.95 (d, 3H,
J = 8Hz, pyrazolyl-5H), 8.21 (d, 3H, J= 8 Hz, pyrazolyl-
4H), 9.94 (br.s, 3H, 3NH). MS m/z (%) 357 (M+ + 1, 23),
356 (M+, 100), 355 (43), 330 (25), 328 (21), 304 (48),
143 (27), 114 (25), 77 (26). Anal. Calcd. for C19H16N8
(356.38): C, 64.03; H, 4.53; N, 31.44. Found: C, 64.03;
H, 4.53; N, 31.44%
3,4-Bis[3-ethoxycarbonyl-2-methyl-pyridin-6-yl]-5-methyl-1-
(4-[3-ethoxycarbonyl-2-methyl-pyridin-6-yl]phenyl)-1H-pyrazole
(14a). Brown solid, (80% yield), mp 82–84°C, IR (KBr)
ν
max/cmꢀ1 1712 (C¼O). 1H NMR (DMSO-d6) δ 1.32 (t, J=
7Hz, 9H, 3CH3), 2.32 (s, 3H, CH3), 2.68 (s, 9H, 3CH3),
4.31 (q, J=7Hz, 6H, 3CH2), 7.77 (d, J=9Hz, 3H, Pyridine-
H), 7.87 (d, J=9Hz, 3H, Pyridine-H), 8.02–8.37 (m, 4H,
ArH). Anal. Calcd. For C37H37N5O6 (647.72) C, 68.61; H,
5.76; N, 10.81. Found C, 68.45; H, 5.52; N, 10.64%.
REFERENCES AND NOTES
[1] Abu Shanab, F. A.; Sherif, S. M.; Mousa, S. A. J Heterocylic
Chem 2009, 46, 801.
[2] Riyadh, S. M.; Abdelhamid, I. A.; Al-Matar, H. M.; Hilmy, N. M.;
Elnagdi, M. H. Heterocycles 2008, 75, 1849.
[3] Edafiogho, I. O.; Kombian, S. B.; Ananthalakshmi, K. V.;
Salama, N. N.; Eddington, N. D.; Wilson, T. L.; Alexander, M. S.;
Jackson, P. L.; Hanson, C. D.; Scott, K. R. J Pharm Sci 2007, 96, 2509.
[4] Svete, J. Arkivoc 2006, vii, 35.
[5] Palmieri, G.; Cimarelli, C. Arkivoc 2006, (vi), 104.
[6] Alnajjar, A.-A.; Abdelkhalik, M. M.; Al-Enezi, A.;
Elnagdi, M. H. Molecules 2009, 14, 68.
[7] Al-Saleh, B.; El-Apasery, M. A.; Abdel-Aziz, R. S.;
Elnagdi, M. H. J Heterocylic Chem 2005, 42, 563.
[8] Al-Mousawi, S.; Abdelkhalik, M. M.; John, E.; Elnagdi, M. H.
J Heterocylic Chem 2003, 40, 689.
[9] Bejan, E.; Aït-Haddou, H.; Daran, J.-C.; Balavoine, G. G. A.
Eur J Org Chem 1998, 1998, 2907.
[10] Farghaly, T. A.; Abdallah, M. A.; Abdel Aziz, M. R.
Molecules 2012, 17, 14625.
[11] Riyadh, S. M.; Farghaly, T. A.; Abdallah, M. A.; Abdalla, M. M.;
Abdel-Aziz, M. R. Eur J Med Chem 2010, 45, 1042.
3,4-Bis[3-ethoxycarbonyl-2-phenyl-pyridin-6-yl]-5-methyl-1-
4-[3-ethoxycarbonyl-2-phenyl-pyridin-6-yl]phenyl)-1H-pyrazole
(14b). Brown solid, (80% yield), mp 70–72 °C, IR (KBr)
1
ν
max/cmꢀ1 1707 (C¼O). H NMR (DMSO-d6) δ 1.03 (t,
J =7 Hz, 9H, 3CH3), 1.91 (s, 3H, CH3), 4.13 (q, J = 7Hz,
6H, 3CH2), 7.27–7.88 (m, 19H, ArH), 8.0 (d, J = 9Hz,
3H, Pyridine-H), 8.17 (d, J = 9Hz, 3H, Pyridine-H). MS
m/z (%) 833 (M+, 21), 832 (5), 77 (100). Anal. Calcd.
For C52H43N5O6 (833.93) C, 74.89; H, 5.20; N, 8.40.
Found C, 74.67; H, 5.05; N, 8.21%.
Reaction of enaminone 4 with heterocyclic amines. To a
solution of 4 (2.25 g, 0.005 mole) in acetic acid (20 mL) was
added the appropriate heterocyclic amine (0.005mole). The
mixture was refluxed for 6 h then cooled. The solid that
deposited after cooling was filtered off and crystallized from
the appropriate solvent. The physical constants together with
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet