9
26
R. Reddy Sagyam, H. Vurimidi, P. Reddy Padi and M. Reddy Ghanta
Vol 44
1
1
663 (amide C=O), H nmr (DMSO-d , ꢀ ppm): 1.01 (d, 3H,
and washed with 10% sodium bicarbonate solution (2 x 15 mL)
followed by water (10 mL). The organic layer was separated and
concentrated under vacuum, the resulting solid was
recrystallised from ethyl acetate and diethyl ether (1:1).
6
CH ), 1.23 (d, 3H, CH ), 2.88 (m, 1H, CH) 5.53 (s, 1H, CH),
3
3
6
.8-7.2 (m, 10H, Ar-H), 10.2 (s, 1H, NH).
-[2-(4-Fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-
N-phenylpentanamide (6). A mixture of 5 (10 g, 0.034 mole),
-ethyl-5-(2-hydroxyethyl)-4-methyl-3-thiazolium bromide (8.3
g, 0.033 mole), 4-fluoro benzaldehyde (5.6 g, 0.045 mole) and
triethyl amine (7.6 g, 0.075 mole) were maintained at 65-70°C
for 10-14 hours (vide TLC) under neat reaction conditions.
Isopropyl alcohol was added (25 mL) and the reaction mixtures
was cooled to room temperature and maintained for 3-4 hours.
The obtained solid was collected by filtration, washed with
isopropyl alcohol (10 mL), and dried to give compound 6 in
4% yield as white solid, mp 206-209°C; ir (cm ): 3295 (NH),
721, 1683(C=O), 1652, 1598 (amide C=O). H nmr (DMSO-d ,
ppm): 0.94 (d, 3H, CH ), 1.17 (d, 3H, CH ), 2.91 (m, 1H, CH),
.88 (d, 1H, CH), 5.43 (d, 1H, CH), 6.98-7.39 (m, 12H, Ar-H),
.10-8.17(d, 2H, Ar-H), 10.19 (s, 1H, NH); C nmr (DMSO-d6,
ppm): 17.88, 18.81, 38.92, 51.82, 63.07, 115.71, 119.64,
23.87, 127.47, 128.58, 128.81, 131.70, 132.18, 135.08, 138.10,
2
Acknowledgement. The authors wish to thank the
management of Dr. Reddy's Laboratories Limited for providing
facilities to carry out this work and co-operation extended by all
the colleagues is gratefully acknowledged.
3
REFERENCES AND NOTES
[1] (a) Comprehensive Heterocyclic Chemistry; Bird, C.W. Ed.;
Pergamon Press: Oxford, 1996; Vol. 2. For some recent examples on
biological activity of pyrrole derivatives, see: (b) Micheli, F.; Di Fabio,
R.; Cavanni, P.; Rimland, J. M.; Capelli, A. M.; Chiamulera, C.; Corsi,
M.; Corti, C.; Donati, D.; Feriani, A.; Ferraguti, F.; Maffeis, M.; Missio,
A.; Ratti, E.; Paio, A.; Pachera, R.; Quartaroli, M.; Reggiani, A.;
Sabbatini, F. M.; Trist, D. G.; Ugolini, A.; Vitulli, G. Bioorg. Med.
Chem. 2003, 11, 171. (c) Mach, R. H.; Huang, Y. S.; Freeman, R. A.;
Wu, L.; Blair, S.; Luedtke, R. R. Bioorg. Med. Chem. 2003, 11, 225. (d)
Bleicher, K. H.; Wuthrich, Y.; Adam, G.; Hoffmann, T.; Sleight, A. J.
Bioorg. Med. Chem. Lett. 2002, 12, 3073. (e) Hackling, A. E.; Stark, H.
Chem. Bio-Chem. 2002, 3, 946. (f) El-Gaby, M. S. A.; Gaber, A. M.;
Atalla, A. A.; Al-Wahab, K. A. A. Farmaco 2002, 57, 613.
-
1
8
1
ꢀ
4
8
ꢀ
1
1
1
6
3
3
13
64.93,164.97, 196.38, 207.99.
General procedure for the preparation of compounds (7a-7l).
Method A. A mixture of 2-[2-(4-fluorophenyl)-2-oxo-1-
phenylethyl]-4-methyl-3-oxo-N-phenylpentanamide (6, 1.0 g,
.0024 mole), the appropriate amine (0.0029 mole) and p-
toluenesulfonic acid (0.2 g, 0.0011 mole) in cyclohexane (20
mL) was maintained at reflux until completion of the reaction
vide TLC). The reaction mixture was then cooled to 30 °C,
[
2] (a) O'Hagan, D. Nat. Prod. Rep. 2000, 17, 435 and references
therein. (b) Hoffmann, H.; Lindel, T. Synthesis 2003, 1753. (c) Fu¨rstner,
A. Angew. Chem., Int. Ed. 2003, 42, 3582. (d) Lindquist, N.; Fenical,
W.; Van Duyne, G. D.; Clardy, J. J. Org. Chem. 1988, 53, 4570. (e)
Boger, D.; Boyce, C. W.; Labroli, M. A.; Sehon, C. A.; Jin, Q. J. Am.
Chem. Soc. 1999, 121, 54.
0
(
dissolved in ethyl acetate (5 mL) and the resulting solution
washed with 10 % sodium bicarbonate solution (2 x 10 mL)
followed by water (10 mL). The organic layer was separated and
concentrated under vacuum and the resulting residue was
triturated with the appropriate solvent (10-15 mL) and
recrystallised (Table-2).
[3] (a) Colotta, V.; Cecchi, L.; Melani, F.; Filacchioni, G.;
Martini, C.; Giannaccini, G.; Lucacchini, A. J. Med. Chem. 1990, 33,
2
646. (b) Cozzi, P.; Mongelli, N. Curr. Pharm. Des. 1998, 4, 181. (c)
Huffman, J. W. Curr. Med. Chem. 1999,6, 705.
4] (a) Curran, D.; Grimshaw, J.; Perera, S. D. Chem. Soc. Rev.
[
1
1
991, 20, 391. (b) Deronzier, A.; Moutet, J. -C. Curr. Top. Electrochem.
994, 3, 159. (c) Lee, C. F.; Yang, L. M.; Hwu, T. Y.; Feng, A. S.;
Method B. To a solution of 2-[2-(4-fluorophenyl)-2-oxo-1-
phenylethyl]-4-methyl-3-oxo-N-phenylpentanamide (6, 1.0 g,
Tseng, J. C.; Luh, T. Y. J. Am. Chem. Soc. 2000, 122, 4992 and
references therein.
0
.0024 mole), ethanol (5 mL) and acetic acid (5 mL), the
[5] (a) Knorr, L. Chem. Ber. 1884, 17, 1635. (b) Paal, C. Chem.
Ber. 1885, 18, 367. (c) Amarnath, V.; Anthony, D. C.; Amarnath, K.;
Valentine, W. M.; Wetterau, L. A.; Graham, D. G. J. Org. Chem. 1991,
appropriate amine (0.0029 mole) was added and the mixture was
refluxed on oil-bath till the completion of the reaction (vide
TLC). The reaction mixture was cooled to 30 °C, dissolved in
ethyl acetate (20 mL) and washed with 10% sodium bicarbonate
solution (2 x 10 mL) followed by water (10 mL). The organic
layer was separated, concentrated under vacuum and the
obtained residue was triturated with appropriate solvent and
recrystallised (Table-2).
5
6, 6924. (d) Pyrroles, Part II; Jones, R. A. 1992, Wiley Ed: New York,.
(e) Gribble, G. W. In Comprehensive Heterocyclic Chemistry II;
Katrizky, A. R.; Rees, C. W.; Scriven, E. F. Eds. Pergamon Press:
Oxford, 1996; Vol. 2, p 207. For a solid-phase approach to the synthesis
of pyrroles from 1,4-dicarbonyl compounds, see: Raghavan, S.;
Anuradha, K. Synlett 2003, 711.
[6] Merlic, C. A.; Baur, A.; Aldrich, C. C. J. Am. Chem. Soc.
2
000, 122, 7398.
7] Kel'in, A. V.; Sromek, A. W.; Gevorgyan, V. J. Am. Chem.
Soc. 2001, 123, 2074.
General procedure for the preparation of bis pyrrole
derivatives (8a-8c). A mixture of 2-[2-(4-fluorophenyl)-2-oxo-
[
1
0
-phenylethyl]-4-methyl-3-oxo-N-phenylpentanamide (6, 1.0 g,
.0024 mole), appropriate diamine (0.006 mole) and acetic acid
[8] Wang, Y. L.; Zhu, S. Z. Org. Lett. 2003, 5, 745.
9] Takaya, H.; Kojima, S.; Murahashi, S. I. Org. Lett. 2001, 3,
[
(3 mL) in toluene and cyclohexane (30 mL, 1:1 mixture) was
4
21.
[10] Butler, D. E.; Deering, C. F.; Millar, A.; Nanninga, T. N.;
Roth, B. D. WO 89/07598, 1989, Chem. Abstr. 1989, 112, 216691.
maintained at reflux for 10-15 hours (vide TLC). The reaction
mixture was cooled to 30 °C, dissolved in ethyl acetate (20 mL)