4784 Journal of Medicinal Chemistry, 2006, Vol. 49, No. 15
Brief Articles
(100). Anal. (C19H16O4) C, H, N: calcd, C 74.01, H 5.23; found,
C 73.64, H 5.38.
References
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1-Oxo-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carboxy-
lic Acid Ethyl Ester (14c). To a mixture of ethyl benzoylacetate
(27.6 g, 161.28 mmol), K2CO3 (44.58 g, 322.56 mmol), and NaI
(29 g, 193.54 mmol) in DMF was added 3-chloromethylphenol
(27.6 g, 193.54 mmol). After 5 h at room temperature, sat. NH4Cl
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purified by silica gel column chromatography to give 2-(3-
hydroxybenzyl)-3-oxo-3-phenylpropionic acid ethyl ester (46.51 g,
96%): 1H NMR (200 MHz, CDCl3) δ 7.96 (dd, J ) 7.8 Hz, 1.2
Hz, 2H), 7.60-7.40 (m, 3H) 7.11 (t, J ) 7.8 Hz, 1H), 6.80-6.60
(m, 3H), 5.37 (s, 1H), 4.62 (t, J ) 7.3 Hz, 1H), 4.11 (q, J ) 7.1
Hz, 2H), 3.26 (d, J ) 7.3 Hz, 2H), 1.11 (t, J ) 7.1 Hz, 3H); mass
spectrum m/e (relative intensity) 298 (M+, 6), 105 (100). A mixture
of 2-(3-hydroxybenzyl)-3-oxo-3-phenylpropionic acid ethyl ester
(10 g, 33.52 mmol) and polyphosphoric acid (100 g) was stirred
for 2 h at room temperature. The reaction mixture was poured into
water and extracted with ethyl acetate. The extract was dried and
evaporated. The residue was purified by silica gel column chro-
matography to give 6-hydroxy-3-phenyl-1H-indene-2-carboxylic
acid ethyl ester (4.24 g, 45%): 1H NMR (200 MHz, CDCl3) δ
7.45-7.39 (m, 5H), 7.11 (d, J ) 8.4 Hz, 1H), 7.02 (d, J ) 1.8 Hz,
1H), 6.77 (dd, J ) 8.4 Hz, 1.8 Hz, 1H), 5.27 (s, 1H), 4.13 (q, J )
7.2 Hz, 2H), 3.81 (s, 2H), 1.13 (t, J ) 7.1 Hz, 3H); mass spectrum
m/e (relative intensity) 280 (M+, 11), 208 (100), 105 (82). A mixture
of 6-hydroxy-3-phenyl-1H-indene-2-carboxylic acid ethyl ester (5
g, 17.84 mmol) and SeO2 (19.8 g, 278.37 mmol) in 1,4-dioxane
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temperature and diluted with 1 M NaHCO3 and ether. The organic
layer was dried and evaporated. The residue was purified by silica
gel column chromatography to give 6-hydroxy-3-phenyl-1H-indene-
2-carboxylic acid ethyl ester (2.83 g, 54%): 1H NMR (200 MHz,
CDCl3) δ 7.50 (s, 5H), 7.11 (d, J ) 2.2 Hz, 1H), 7.02 (d, J ) 8.1
Hz, 1H), 6.77 (dd, J ) 8.1 Hz, 2.2 Hz, 1H), 4.17 (q, J ) 7.2 Hz,
2H), 1.14 (t, J ) 7.1 Hz, 3H); mass spectrum m/e (relative intensity)
294 (M+,57), 249 (99), 222 (100). To a mixture of 6-hydroxy-3-
phenyl-1H-indene-2-carboxylic acid ethyl ester (2 g, 6.79 mmol),
K2CO3 (1.41 g, 10.19 mmol), and NaI (0.2 g, 1.40 mmol) in DMF
was added 1-bromo-3-phenylpropane (2.07 mL, 13.59 mmol). After
8 h at room temperature, sat NH4Cl solution was added, and the
mixture was extracted with ethyl acetate. The extract was dried
and evaporated. The residue was purified by silica gel column
chromatography to give 1-oxo-3-phenyl-6-(3-phenylpropoxy)-1H-
indene-2-carboxylic acid ethyl ester (2.37 g, 85%): 1H NMR (200
MHz, CDCl3) δ 7.51 (s, 5H), 7.36-7.21 (m, 6H), 7.06 (d, J ) 8.1
Hz, 1H), 6.83 (dd, J ) 8.1 Hz, 2.4 Hz, 1H), 4.17 (q, J ) 7.2 Hz,
2H), 4.00 (t, J ) 6.3 Hz, 2H), 1.14 (t, J ) 7.4 Hz, 2H), 2.16-2.05
(m, 2H), 1.15 (t, J ) 7.1 Hz, 3H); mass spectrum m/e (relative
intensity) 412 (M+, 14), 91 (100); Anal. (C27H24O4) C, H, N: calcd,
C 78.62, H 5.86; found, C 78.90, H 5.82.
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Acknowledgment. This research was supported by the
Center for Biological Modulators of the 21st Century Frontier
R&D Program, the Ministry of Science and Technology, Korea.
The authors thank the Korea Chemical Bank for use of the
chemical library for HTS. The authors also thank Dr. H. S. Lee
and the staff at the Pohang Accelerator Laboratory for help with
data collection.
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Supporting Information Available: Synthetic procedure for
1
compounds including the H NMR, mass, and elemental analysis
data, biological procedures, and X-ray cocrystal structure determi-
nation. This material is available free of charge via the Internet at
JM060389M