372
A. Shafiee, J. S. Mojarrad, M. A. Jalili, H. R. Adhami and F. Hadizadeh
Vol. 39
Compound 11a has ir (sodium chloride disk): ν 2960 (CH,
CHO), 1720 (C=O, ester), 1680 cm (C=O, CHO); H-nmr (deu-
Anal. Calcd. for C H N O : C, 69.60; H, 5.80; N, 9.74.
25 25 3 4
Found: C, 69.23; H, 5.97; N, 9.93.
-1
1
teriochloroform): δ 9.84 (s, 1H, CHO), 7.92 (d, 1H, aromatic
Methyl 2-(n-Butyl)-1-[(2'-carbomethoxybiphenyl-4-yl)methyl]-
pyrrolo[2,3-d]imidazole-5-carboxylate (14b).
J=8Hz), 7.58 (s, 1H, HC imidazole), 7.50-7.10 (m, 7H, aro-
5
matic), 5.15 (s, 2H, NCH ), 3.70 (s, 3H, OCH ), 2.75 (t, 2H,
2
3
This compound was prepared in a similar fashion to 14a afford-
ing 14b as a white solid in 32% yield; mp 174-175 °C; ir (potas-
sium bromide): ν 3380 (NH), 1715 (C=O), 1700 cm (C=O); H-
nmr (deuteriochloroform): δ 9.85 (bs, 1H, NH), 7.85 (d, 1H, aro-
matic, J=8 Hz), 7.50-7.20 (m, 7H, aromatic), 6.44 (s, 1H, HC pyr-
CH , J=7.4 Hz), 1.80-1.40 (m, 2H, CH ), 1.00 ppm (t, 3H, CH ,
J=7.4 Hz).
2
2
3
-1
1
Anal. Calcd. for C
H N O : C, 72.93; H,6.08; N, 7.73.
22 22 2 3
Found: C, 72.67; H, 5.99; N, 7.59.
Compounds 10b and 11b were prepared similarly (Table 2).
role), 5.25 (s, 2H, NCH ), 3.83 (s, 3H, OCH ) 3.61 (s, 3H, OCH ),
2
3
3
Methyl α-Azido-β-[1-[(2'-carbomethoxybiphenyl-4-yl)methyl]-
2-propylimidazol-5-yl]acrylate (12a).
2.93 (t, 2H,CH , J=7.4 Hz), 2.10-1.70 (m, 2H, CH ), 1.60-1.30
2
2
(m, 2H, CH ), 0.90 ppm (t, 3H, CH , J=7.2 Hz); ms: m/z (%) 445
2
3
+
(M , 14), 225 (100), 178 (83), 165 (46), 152 (11), 44 (17).
Anal. Calcd. for C N O : C, 70.11; H, 6.07; N, 9.44;
To a stirred solution of sodium (0.46 g, 20 mmoles) in absolute
methanol (8 ml) at -15 °C was added dropwise a solution of 10a
(1.8 g, 5 mmoles) and methyl azido acetate (1.3 g, 20 mmoles) in
absolute methanol (4 ml). After two hours at -15 °C, the mixture
was added to a saturated solution of ammonium chloride. The
mixture was extracted with ether. The organic layer was washed
once with water and dried (anhydrous sodium sulfate). The ether
was evaporated and the residue was purified by column chro-
matography on silica gel (petroleum ether-chloroform; 80:20 as
eluent) to give 0.9 g (40%) of 12a as an pale yellow oil. ir
H
26 27
3 4
Found: C, 69.71; H, 6.28; N, 9.67.
Methyl 2-(n-Butyl)-1-[(2'-carbomethoxybiphenyl-4-yl)methyl]-
pyrrolo[3,2-d]imidazole-5-carboxylate (15b).
This compound was prepared in a similar fashion to 14a
affording 15b as a white solid in 35% yield; mp 187-188 °C; ir
-1
(potassium bromide): ν 3280 (NH), 1725 (C=O), 1650 cm
1
(C=O); H-nmr (deuteriochloroform): δ 9.15 (bs, 1H, NH), 7.85
(d, 1H, aromatic J=8 Hz), 7.50-7.20 (m, 7H, aromatic), 6.92 (s,
1H, HC pyrrole), 5.23 (s, 2H, NCH ), 3.77 (s, 3H, OCH ), 3.69
(sodium chloride disk): ν 2120 (N ), 1720 (C=O, esters), 1620
3
-1
1
2
3
cm (C=C); H-nmr (deuteriochloroform): δ 8.00 (s, 1H, HC
4
(s, 3H, OCH ),2.83 (t, 2H, CH , J=7.4 Hz), 2.10-1.70 (m, 2H,
3
2
imidazole), 7.92 (d, 1H, aromatic, J=8 Hz), 7.50-7.10 (m, 7H,
aromatic), 6.74 (s, 1H, H ), 5.25 (s, 2H, NCH ), 3.85 (s, 3H,
CH ), 1.65-1.35 (m, 2H, CH ), 0.95 ppm (t, 3H, CH , J=7.2 Hz);
2
2
3
β
2
+
ms: m/z (%) 445 (M , 6), 225 (100), 178 (92), 165 (46), 97 (7).
Anal. Calcd. for C N O : C, 70.11; H, 6.07; N, 9.44.
OCH ), 3.65 (s, 3H, OCH ), 2.72 (t, 2H, CH , J=7.4 Hz), 1.90-
3
3
2
H
26 27
3 4
1.50 (m, 2H, CH ), 1.00 ppm (t, 3H, CH3, J=7.4 Hz).
2
Found: C, 69.81; H, 6.29; N, 9.27.
Anal. Calcd. fo\r C
H N O : C, 65.36; H, 5.45; N, 15.25.
25 25 5 4
Found: C, 64.99; H, 5.37; N, 15.50.
Compounds 12b and 13a,b were prepared similarly (Table 3).
Acknowledgements.
This work was supported by grants from the Research Council
of Tehran University of Medical Sciences and the International
Organization for Chemical Sciences in Development (IOCD).
Methyl 2-(n-Propyl)-1-[(2'-carbomethoxybiphenyl-4-yl)methyl]-
pyrrolo[2,3-d]imidazole-5-carboxylate (14a).
A solution of 12a (2.8 g, 6.1 mmoles) in xylene (40 ml) was
refluxed for 2 hours. The solvent was evaporated and the residue
was purified by column chromatography on silica gel (petroleum
ether-chloroform 50:50) and then it was crystallized from diethyl
ether to give 0.84 g (32%) of 14a as a white solid, mp188-190 °C;
REFERENCES AND NOTES
[1] H. Yanagisawa, Y. Amemiya, T. Kanazaki, Y. Shimajy, K.
Fujimoto, Y. Kitahara, T. Sada, M. Mizuno, M. Ikeda, S. Migamoto,
Y. Furukawa and H. Koike, J. Med. Chem., 39, 323 (1996).
[2] C. Almansa, L. A. Gomes, F. L. Gavalcanti, A. F. de
Arriba, J. Garcia-Rafanell and J. Forn, J. Med. Chem., 40, 547
(1997).
-1
ir (potassium bromide): ν 3380 (NH), 1730 (C=O), 1690 cm
1
(C=O); H-nmr (deuteriochloroform): δ 10.61 (bs, 1H, NH), 7.85
(d, 1H, aromatic, J=8 Hz), 7.50-7.20 (m, 7H, aromatic): 6.32 (s,
1H, HC pyrrole), 5.31 (s, 2H, NCH ), 3.83 (s, 3H, OCH ), 3.65
2
3
[3] R. M. Keenan, J. Weinstock, J. A. Finkelstein, R. G. Franz,
D. E. Gaitanopoulos, G. R. Girard, D. T. Hill, T. M. Morgan, J. M.
Samanen, C. E. Peishoff, L. M. Tucker, N. Aiyar,E. Griffin, E. H.
Ohlstein, E. J. Stack, E. F. Weidley and R. M. Edwards, J. Med.
Chem., 36, 1880 (1993).
[4] J. V. Duncia, A. T. Chiu, D. J. Carini, G. B. Gregory, A. L.
Johnson, W. A. Price, G. J. Wells, P.C. Wong, J.C. Calabrese and
P.B.M.W.M. Timmermans, J. Med. Chem., 33, 1312 (1990).
[5] M. Fortin, D. Frechet, G. Hamon,S. Jouquey, J.P. Veven;
Eur. Pat. Appl. Ep 461, 040 (1991), Chem. Abstr. 116; 151760n
(1992).
(s, 3H, OCH ), 2.81 (t, 2H, CH , J=7.4 Hz), 1.90-1.50 (m, 2H,
3
2
+
CH ), 1.00 ppm (t, 3H, CH , J=7.4 Hz); ms: m/z (%) 431 (M ,
2
3
14), 225 (100), 165 (50), 152 (11).
Anal. Calcd. for C N O : C, 69.60; H, 5.80; N, 9.74.
H
25 25
3 4
Found: C, 69.37; H, 5.69; N, 9.92.
Methyl 2-(n-Pyropyl)-1-[2'-carbomethoxybiphenyl-4-yl)-
methyl]pyrrolo[3,2-d]imidazole-5-carboxylate (15a).
This compound was prepared in a similar fashion to 14a
affording 15a as a white solid in 39% yield; mp 196-198 °C; ir
-1
(potassium bromide): ν 3280 (NH), 1720 (C=O), 1645 cm
[6] N. B. Mantlo, P. K. Chakravarty, D. L. Ondeyka, P. K. S.
Sieg, R. S. Chang, V. J. Lotti, K. A. Faust, T. B.Chen, T. W. Schorn,
C. S. Sweet, S. E.Emmert, A. A.Patchett, W. J.Greenlee, J. Med.
Chem. 34, 2919 (1991).
1
(C=O); H-nmr (deuteriochloroform): δ 11.40 (bs, 1H, NH), 7.72
(d, 1H, aromatic, J=8Hz) 7.50-7.10 (m, 7H, aromatic), 6.84 (s,
1H, HC pyrrole), 5.25 (s, 2H, NCH ), 3.75 (s, 3H, OCH ), 3.65
2
3
(s, 3H, OCH ), 2.71 (t, 2H, CH , J=7.4 Hz), 1.90-1.50 (m, 2H,
[7] A. P. Thomas, C. P. Allott, K. H. Gibson, J. S. Major, B. B.
Masek, A. A. Oldham, A. H. Ratcliffe, D. A. Roberts, S. T. Russell,
and D. A. Thomason, J. Med. Chem. 35, 877 (1992).
3
2
+
CH ), 0.95 ppm (t, 3H, CH , J=7.4 Hz); ms: m/z (%) 431 (M , 8),
2
3
225 (100), 165 (54), 152 (13).