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T. Mano et al.
PAPER
Mp 100–105 °C.
IR (KBr): 2210 (C≡N) cm–1.
References
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1H NMR (270 MHz, CDCl3): d = 7.56 (d, 2 H, J = 8.4 Hz, aromat-
ic), 7.35 (d, 2 H, J = 8.4 Hz, aromatic), 7.04 (d, 1 H, J = 1.5 Hz, im-
idazole), 7.02 (d, 1 H, J = 1.5 Hz, imidazole), 6.97 (br s, 1 H,
aromatic), 6.82 (ddd, 1 H, J = 9.5, 2.2, 1.8 Hz, aromatic), 6.69 (ddd,
1 H, J = 9.5, 2.2, 1.8 Hz, aromatic), 5.13 (s, 2 H, benzylic CH2),
4.16–4.02 (m, 2 H, THP CH2), 3.97–3.81 (m, 2 H, THP CH2), 2.39
(s, 3 H, CH3), 2.20–1.98 (m, 4 H, THP CH2).
(2) Henderson, W. R. Jr. J. Allergy Clin. Immunol. 1987, 79,
543.
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Medicinal Chemistry, Vol. 24; Allen, R. C., Ed.; Academic
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MS (ESI+): m/e = 392 (M + H)+.
Anal. Calcd for C23H22FN3O2·0.3 H2O: C, 69.61; H, 5.74; N, 10.59.
Found: C, 69.71; H, 5.63; N, 10.29.
4-(3-Fluoro-5-{[4-(2-methyl-1H-imidazol-1-yl)benzyl]oxy}phe-
nyl)tetrahydro-2H-pyran-4-carboxamide (1)5
To the stirred solution of 14 (28.9 g, 72.2 mmol) in t-BuOH (300
mL), powdered KOH (85%, 12.4 g, 221 mmol) was added and the
mixture was stirred at 80 °C for 4 h, then volatile was removed un-
der reduced pressure. H2O (200 mL) was added to the residue and
the resulting precipitates were collected by suction filtration,
washed with water (2 × 100 mL), and dried under vacuum to afford
27.1 g (92%) of the title compound as a white solid with 98.9% pu-
rity (HPLC).
Mp 207–208 °C.
IR (KBr): 1668 (C=O) cm–1.
1H NMR (270 MHz, DMSO-d6): d = 7.61 (d, 2 H, J = 8 Hz, aromat-
ic), 7.48 (d, 2 H, J = 8 Hz, aromatic), 7.30 (d, 1 H, J = 1 Hz, imida-
zole), 7.24 (br s, 1 H, NH2), 7.08 (br s, 1 H, NH2), 6.92 (d, 1 H, J = 1
Hz, imidazole), 6.89–6.82 (m, 2 H, aromatic), 6.80–6.75 (m, 1 H,
aromatic), 5.18 (s, 2 H, benzylic CH2), 3.66–3.57 (m, 2 H, THP
CH2), 3.51–3.40 (m, 2 H, THP CH2), 2.44–2.35 (m, 2 H, THP CH2),
2.29 (s, 3 H, CH3), 1.84–1.72 (m, 2 H, THP CH2).
(13) Katritzky, A. R.; Pilarski, B.; Urogdi, L. Synthesis 1989,
949.
MS (ESI+): m/e = 410 (M + H)+.
Anal. Calcd for C23H24FN3O3: C, 67.47; H, 5.91; N, 10.26. Found:
C, 67.45; H, 5.97; N, 10.26.
(14) (a) Hall, J. H.; Gisler, M. J. Org. Chem. 1976, 41, 3769.
(b) Popov, S. A.; Rukavishnikov, A. V.; Tkachev, A. V.
Synthesis 1992, 783. (c) Felpin, F.-X.; Doris, E.; Wagner,
A.; Valleix, A.; Rousseau, B.; Mioskowski, C. J. Org. Chem.
2001, 66, 305. (d) Engler, T. A.; Furness, K.; Malhotra, S.;
Sanchez-Martinez, C.; Shih, C.; Xie, W.; Zhu, G.; Zhou, X.;
Conner, S.; Faul, M. M.; Sullivan, K. A.; Kolis, S. P.;
Brooks, H. B.; Patel, B.; Schultz, R. M.; DeHahn, T. B.;
Kirmani, K.; Spencer, C. D.; Watkins, S. A.; Considine, E.
L.; Dempsey, J. A.; Ogg, C. A.; Stamm, N. B.; Anderson, B.
D.; Campbell, R. M.; Vasudevan, V.; Lytle, M. L. Bioorg.
Med. Chem. 2003, 13, 2261.
Acknowledgment
The authors would like to express their gratitude to Hideyuki Aoya-
ma, Yoshihiro Hirayama, Jinsong Niu and Mineko Taguchi for their
analytical support in elemental analysis, mass and infrared spectro-
metry measurements.
Synthesis 2004, No. 16, 2625–2628 © Thieme Stuttgart · New York