H. E. Master et al. / Bioorg. Med. Chem. 13 (2005) 4891–4899
4899
2
.15. 3-Phenoxycinnamic acid (41)
(C@O), 1616 (C@C, alkenes), 1507, 1424 (C@C, aro-
1
matic); H NMR (CDCl , d ppm): 6.4–6.8 (d, 2H),
3
+
7.6–8.4 (m, 7H); MS: m/z 198 (M ).
1.95 g (7.575 mmol) 3-phenoxybenzaldehyde (4) and
malonic acid (0.945 g, 9.09 mmol) was heated to 80–
9
0 °C in pyridine (1.212 g, 15.15 mmol) in the presence
of piperidine (0.0774 g, 0.909 mmol). The resulting mix-
ture was poured over ice-cold 3 ml concentrated hydro-
chloric acid and was stirred to obtain the desired
References and notes
1. Frank, M. M.; Fries, L. F. Immunol. Today 1991, 12, 322–
326.
2. Gasque, P.; Dean, Y. D.; McGreal, E. P.; VanBeeK, J.;
Morgan, B. P. Immunopharmacology 2000, 49, 171–186.
3. Kaufman, T. S.; Srivastava, R. P.; Sindelar, R. J. Med.
Chem. 1995, 38, 1437–1445.
cinnamic acid derivative (41) as a white solid (1.45 g,
8
À1
0%). IR (cm ) (KBr pellet): 1694 (C@O), 1633
(
C@C, alkene), 1566, 1471 (C@C, aromatic), 1221 (un-
1
sym C–O–C). H NMR (CDCl , d ppm): 6.4–6.6
(
3
+
d, 2H), 7.2–8.0 (m, 9H); MS: m/z 240 (M ).
4
. Lee, S. M.; Park, J. G.; Lee, Y. H.; Lee, C. G.; Min, B. S.;
Kim, J. H.; Lee, H. K. Biol. Pharm. Bull. 2004, 27, 1883–
2
.16. 3,4-Dichlorocinnamic acid (42)
1
886.
5
. Mqadmi, A.; Zheng, X.; Song, J.; Abramovitz, S.; Giclas,
P.; Yazdanbaksh, K. Biochem. Biophys. Res. Commun.
2004, 325, 1465–1471.
Following the same procedure as given in example 16;
,4-dichlorobenzaldehyde (19) (1.0 g, 5.7143 mmol)
3
was treated with malonic acid (0.713 g, 6.857 mmol) in
pyridine (0.914 g, 11.43 mmol) and in the presence of
piperidine (0.058 g, 0.6857 mmol) yielding compound
6. Roos, A.; Nauta, A. J.; Broers, D.; Faber-Krol, M. C.;
Trouw, L. A.; Drijfhout, J. W.; Daha, M. R. J. Immunol.
2
001, 167, 7052–7059.
À1
7. Hagmann, W. K.; Sindelar, R. D. In Annual Reports in
Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press:
San Diego, 1992, pp 199–208.
4
2 in quantitative yield (1.24 g, 85%). IR (cm ) (KBr
pellet): 1694 (C@O), 1622 (C@C, alkenes), 1553, 1472
1
(
(
C@C, aromatic). H NMR (CDCl , d ppm): 6.2–6.6
3
8
. Patrick, R. A.; Johnson, R. E. In Annual Reports in
Medicinal Chemistry; Hess, H.-J., Ed.; Academic Press:
New York, 1980, pp 193–201.
+
d, 2H), 7.6 (m, 3H); MS: m/z 217 (M ).s
2
.17. 2,3-Dimethoxycinnamic acid (43)
9
. Asghar, S. S. Pharmacol. Rev. 1984, 36, 223.
1
0. Sunyer, J. O.; Zarkadis, I. K.; Lambris, J. D. Immunol.
Today 1998, 19, 519.
Following the same procedure as given in example 16;
,3-dichlorobenzaldehyde (17) (1.3 g, 7.83 mmol) was
2
11. Sahu, A.; Lambris, J. D. Immunopharmacology 2000, 49,
33–148.
1
treated with malonic acid (0.977 g, 9.396 mmol) in pyri-
dine (1.253 g, 15.66 mmol) and in the presence of piper-
idine (0.08 g, 0.9396 mmol) yielding compound 43 in
1
2. Assefa, H.; Nimrod, A.; Walker, L.; Sindelar, R. Bioorg.
Med. Chem. Lett. 2001, 11, 1619–1623.
À1
13. Pieters Luc, A. C.; De Bruyne Tess, E.; Vlietinck Arnold,
J. In Immunomodulatory Agents from Plants; Verlag:
Basel, Switzerland, 1999.
quantitative yield (1.44 g, 89%). IR (cm ) (KBr pellet):
1
aromatic), 1266 (unsym C–O–C), 950 (O–H bend); H
684 (C@O), 1634 (C@C, alkenes), 1576, 1484 (C@C,
1
1
4. Asghar, S. S.; Pasch, M. C. Front. Biosci. 1995, 5, e63–
e81.
NMR (CDCl , d ppm): 3.8–4.0 (s, 6H), 6.4–6.8 (d,
3
+
H), 7.0–7.2 (m, 3H); MS: m/z 207 (M ).
2
15. Becker, E. L. In Complement, ed.; 1965, pp 58–73.
1
6. Master, H. E.; Khan, S. I.; Poojari, K. A. Bioorg. Med.
Chem. Lett. 2003, 13, 1249.
2
.18. 2,6-Dichlorocinnamic acid (44)
1
7. Singh, H.; Chawla, A. S.; Kapoor, V. K.; Paul, D.;
Malhotra, R. K. In Progress in Medicinal Chemistry;
Ellis, G. P., West, G. B., Eds.; Elsevier/North-Holland
Biochemical Press: Amsterdam, 1980; Vol. 17, Chapter
Following the same procedure as given in example 16;
,5-dichlorobenzaldehyde (18) (0.85 g, 4.857 mmol)
2
was treated with malonic acid (0.6 g, 5.828 mmol) in
pyridine (0.777 g, 9.714 mmol) and in the presence of
piperidine (0.0496 g, 0.5828 mmol) yielding compound
4
.
1
8. Lipinski, C. A. In Annual Reports in Medicinal Chemistry;
Bailey, U. M., Ed.; Academic Press: Orlando, FL, 1986,
pp 283–291.
À1
4
4 in quantitative yield (0.97 g, 92%). IR (cm ) (KBr
pellet): 1690 (C@O), 1625 (C@C, alkene), 1555, 1465
19. The spectral and analytical data collected for all the final
compounds and intermediates were consistent with the
proposed structures.
1
(
C@C, aromatic); H NMR (CDCl , d ppm): 6.6–6.8
3
+
d, 2H), 7.0–7.6 (m, 3H); MS: m/z 217 (M ).
(
2
2
0. Supniewski, J. V.; Adams, R. JACS 1926, 48, 507.
1. Tietze, L. F.; Eicher, T. Reactions and Synthesis in the
Organic Chemistry Laboratory; University Science Books:
Mill Valley, 1989 (p 379, e.g., O-26).
2
.19. a-Naphthylacrylic acid (45)
Following the same procedure as given in example 16; a-
naphthaldehyde (37) (1.0 g, 6.41 mmol) was treated with
malonic acid (0.8 g, 7.69 mmol) in pyridine (1.025 g,
2
2. Srivastava, R. P.; Zhu, X.; Walker, L. A.; Sindelar, R. D.
Bioorg. Med. Chem. Lett. 1995, 5, 2429.
2
3. Borenfreund, E.; Babich, H.; Martin-Alaguacil, N. In
Vitro Cell. Dev. Biol. 1990, 26, 1030–1034.
1
2.82 mmol) and in the presence of piperidine
0.0655 g, 0.7692 mmol) yielding compound 45 in quan-
(
titative yield (1.2 g, 95%). IR (cm ) (KBr pellet): 1685
24. Assefa, H.; Nimrod, A.; Walker, L.; Sindelar, R. Bioorg.
Med. Chem. Lett. 1999, 9, 1889–1894.
À1