[Synthesis]
The general procedure for the synthesis of (S)-N-((3-(3-(3-fluoro-4-piperazin-1-ylphenyl)-2-oxoxazolidin-5-yl)methyl)-acetamide from the compound (CAS:174649-06-0) is as follows: 0.4 g (0.85 mmol) of Compound 15 and 0.06 g of 10% palladium/carbon catalyst were suspended in a mixture of 19 mL of methanol and 6 mL of dichloromethane in a mixed solvent and the reaction was stirred under hydrogen atmosphere for 48 hours. Upon completion of the reaction, the reaction mixture was filtered through a diatomaceous earth pad to remove the catalyst. The filter cake was washed with 50 mL of dichloromethane followed by 25 mL of ethyl acetate. The filtrates were combined and concentrated to give an off-white solid product. The solid product was ground with 50 mL of 10% methanol-ethyl acetate solvent mixture in a warm water bath for 30 minutes and subsequently cooled to 0°C to promote crystallization. Crystals were collected by filtration to give compound 16 as a white solid. The yield was 91%; melting point was 198-200 °C; IR (KBr) υmax: 3436 and 3329 (NH), 1741 (C=O) and 1644 (CONH) cm-1; 1H NMR (DMSO-d6) δ: 9.03 (br s, 2H, NH2+), 8.26 (t, 1H, J=6 Hz, CONH), 7.50 (dd, 1H, J=15 and 2.5 Hz, H2fluorobenzene), 7.19 (dd, 1H, J=9 and 2.5 Hz, H6fluorobenzene), 7.12 (t, 1H, J=9 Hz, H5fluorobenzene), 4.71-4.68 (m, 1H, H5oxazolidinone), 4.07 (t, 1H, J=9 Hz, CH2NH), 3.69 (dd, 1H. J=9 and 6 Hz, CH2NH), 3.39 (t, 2H, J=6 Hz, H4 oxazolidinone), 3.22-3.21 (m, 4H, piperazine), 3.17-3.16 (m, 4H, piperazine), 1.81 (s, 3H, CH3CO); MS: m/z 337 (45, M+), 295 (100), 250 (53) 191 (32), 57 (32); Calculated values for elemental analysis (C17H24ClFN4O3): C, 52.78; H, 6.25; Cl, 9.16; F, 4.91; N, 14.48. Measured values: C, 52.94; H, 6.10; Cl, 9.24; F, 4.73; N, 14.60. |
[References]
[1] Tetrahedron Letters, 2006, vol. 47, # 38, p. 6799 - 6802 [2] European Journal of Medicinal Chemistry, 2011, vol. 46, # 1, p. 65 - 70 [3] European Journal of Medicinal Chemistry, 2011, vol. 46, # 3, p. 893 - 900 [4] Patent: WO2011/37731, 2011, A1. Location in patent: Page/Page column 118-119 [5] Tetrahedron Letters, 1996, vol. 37, # 44, p. 7937 - 7940 |