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HETEROCYCLES, Vol. 83, No. 8, 2011
reaction mixture was stirred at 15 °C for 20 h and then cooled to 5 °C and stirred at the same temperature for
2h. The precipitated crystals were filtered, washed with acetone (8.80 kg) and dried under reduced pressure
to yield 1 (4.41 kg, 73%, >99.9% ee) as a white crystalline solid.: mp 258-259 °C (decomp); []20D –8.82 (c
1.00, H2O); IR (KCl) 3406, 2983, 2763, 1588, 1324, 1146, 1129 cm-1; 1H-NMR (DMSO-d6) δ: 1.20 (3H, d,
J = 6.6 Hz), 1.98-2.07 (2H, m), 3.06-3.16 (1H, m), 3.22-3.31 (2H, m), 3.35 (4H, s), 3.44 (1H, dd, J = 14.1,
4.4 Hz), 3.59-3.74 (2H, m), 4.37-4.47 (1H, m), 7.93 (1H, t, J = 7.8 Hz), 8.32 (1H, d, J = 7.8 Hz), 8.54-8.60
(1H, m), 8.72 (1H, d, J = 4.9 Hz), 9.39 (1H, s), 9.51 (2H, br s); 13C-NMR (DMSO-d6) δ: 16.6, 26.8, 42.9,
45.5, 50.3, 50.9, 120.9 (J = 12.4 Hz), 127.5, 130.7 (J = 1.7 Hz), 132.2, 132.5 (J = 27.3 Hz), 133.2 (J = 5.0
Hz), 133.3, 149.8 (J = 5.0 Hz), 152.0 (J = 264.0 Hz); FABMS m/z 324 (M+H–HCl–2H2O)+, Anal. Calcd for
C15H23ClFN3O4S: C, 45.51; H, 5.86; Cl, 8.96; F, 4.80; N, 10.61. Found: C, 45.44; H, 5.65; Cl, 8.87; F, 4.68;
N, 10.78.
ACKNOWLEDGEMENTS
We are grateful to Dr. H. Hidaka, CSO, of D. Western Therapeutics Institute for promotion study. We thank
Dr. S. Tanabe, Director, for his encouragement and support and also Dr. K. Mizuno, Manager, for
pharmacology suggestions at Tokyo New Drug Research Laboratories, Kowa Co., Ltd. We also wish to
thank Dr. Kevin Swiss, Director, Kowa Research Institute, for his help in preparing the manuscript.
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