2616 Journal of Medicinal Chemistry, 2009, Vol. 52, No. 8
Brief Articles
C5-H 4-F-Phe), 7.38-7.41 (m, 2H, C3/C5-H Pyr), 7.45-7.52
(m, 2H, C2/C6 4-F-Ph), 7.86 (s, 1H, C2-H imidazole), 8.45 (d,
J ) 5.8 Hz, 2H, C2/C6-H Pyr), 12.76 (bs, 1H, NH); HRMS
(EI): calculated for C14H10FN2 239.0859, found 239.0765.
The crystal structure of 7 has been proven by X-ray analysis:
Enraf-Nonius CAD-4, Cu KR, SIR92, SHELXL97. Further details
of the crystal structure analysis are available in ref 22.
shows interactions with the amino function of the side chain of
Lys53. Maybe an intervening water molecule is playing a role.
Experimental Section
General. All commercially available reagents and solvents
were used without further purification. The microwave reaction
was performed on a CEM Discover system. Melting points were
determined with a Bu¨chi melting point B-545 and are thermo-
dynamically corrected. NMR data were obtained on a Bruker
Spectrospin AC 200 at ambient temperature. High-resolution
spectra were obtained on a Thermo Finnigan TSQ70 instrument.
The purity of the final compounds was determined by HPLC on
a Hewlett-Packard HP 1090 Series II liquid chromatograph using
a Betasil C8 column (150 mm × 4.6 mm i.d., dp ) 5 µm,
Thermo Fisher Scientific, Waltham, MA) at 230 and 254 nm
employing a gradient of 0.01 M KH2PO4 (pH 2.3) and methanol
as the solvent system with a flow rate of 1.5 mL/min; all final
compounds have a purity of >98% (see Supporting Information
for details).
Acknowledgment. The authors thank Dr. A. Liedtke for
helpful discussions, S. Luik, K. Bauer, and M. Goettert for the
assistance in biological testing, and the Alexander von Humboldt
foundation (AvH) for funding.
Supporting Information Available: Full experimental proce-
dures and analytical data for compounds 13-15 and 5-7. This
material is available free of charge via the Internet at http://
pubs.acs.org.
References
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2-(4-Fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole (5). Ammo-
nium acetate (2.2 g, 34.9 mmol) was added to a solution of
compound 14 (0.5 g) in glacial acetic acid (10 mL). The resulting
mixture was heated to 115-120 °C for 2 h. The solvent was
removed under reduced pressure, and the residue was diluted
with ethyl acetate and aq NaHCO3 solution. Solid Na2CO3 was
added until effervescence ceased. The organic phase was washed
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1
steps); Mp 260.8 °C; H NMR (DMSO-d6) 6.43-6.46 (m, 1H,
C4-H pyrrole), 6.92-6.95 (m, 1H, C5-H pyrrole), 7.18-7.27
(m, 4H, C3/C5-H 4-F-Phe, C3/C5-H Pyr), 7.33-7.41 (m, 2H,
C2/C6-H 4-F-Phe), 8.37 (dd, J1 ) 4.6 Hz, J2 ) 1.6 Hz, 2H,
C2/C6-H Pyr), 11.47 (bs, 1H, NH); HRMS (EI): calculated for
C15H11FN2 238.0906, found 238.0897.
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Enraf-Nonius CAD-4, Cu KR, SIR92, SHELXL97. Further details
of the crystal structure analysis are available in ref 20.
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1
over two steps) as a pale yellow solid. Mp 62.1 °C; H NMR
(CDCl3) 6.55-6.56 (m, 1H, C4-H furan), 6.95-7.03 (m, 2H,
C3/C5-H 4-F-Phe), 7.24-7.27 (m, 2H, C3/C5-H Pyr), 7.41-7.48
(m, 3H, C2/C6-H 4-F-Phe, C5-H furan), 8.54 (d, J ) 4.7 Hz,
2H, C2/C6-H Pyr); HRMS (EI): calculated for C15H10OFN
239.0746, found 239.0740.
The crystal structure of 6 has been proven by X-ray analysis:
Enraf-Nonius CAD-4, Cu KR, SIR92, SHELXL97. Further details
of the crystal structure analysis are available in ref 21.
4-(4-Fluorophenyl)-5-(pyridin-4-yl)-1H-imidazole (7). Com-
pound 15 (46 mg, 0.2 mmol), formaldehyde (15 µL, 0.2 mmol,
37% aq solution), ammonium acetate (154 mg, 2,0 mmol), and
1 mL of glacial acetic acid were combined in a reaction vial.
The reaction vessel was heated in a CEM microwave reactor
for 5 min at 180 °C (initial power 200 W), after which a stream
of compressed air cooled the reaction vessel. The reaction
mixture was added dropwise to a concentrated NH4OH solution
at 0 °C. The formed white/colorless precipitate was collected
by filtration, washed with water, and dried. Yield 43 mg (90%);
(17) Boehm, J. C.; Smietana, J. M.; Sorenson, M. E.; Garigipati, R. S.;
Gallagher, T. F.; Sheldrake, P. L.; Bradbeer, J.; Badger, A. M.; Laydon,
J. T.; Lee, J. C.; Hillegass, L. M.; Griswold, D. E.; Breton, J. J.;
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nylimidazoles: a new class of cytokine suppressive drugs with low
1
Mp 258.5 °C; H NMR (DMSO-d6) δ 7.22-7.31 (m, 2H, C3/