Cl.[Cl:2][C:3]1[CH:23]=[CH:22][C:6]([CH2:7][C:8]2[N:9]=[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[S:11][C:12]=2[C:13](=[NH:15])[NH2:14])=[CH:5][CH:4]=1.[O-]CC.[Na+].C([O:30][C:31]([CH:33]=[CH:34][O-])=O)C.[Na+]>C(O)C>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][C:8]2[N:9]=[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[S:11][C:12]=2[C:13]2[NH:14][C:31](=[O:30])[CH:33]=[CH:34][N:15]=2)=[CH:22][CH:23]=1To a solution of 4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole-5-carboximidamide hydrochloride (188 mg, 0.515 mmol) in ethanol (8.0 mL) was added 21% sodium ethoxide in ethanol (0.192 mL, 0.515 mmol) and sodium 2-ethoxycarbonyl ethenolate (284 mg, 2.06 mmol) (prepared as in J. Med. Chem., (2001), 44(17), 2695-2700), and the reaction was heated to reflux overnight. The reaction was cooled and concentrated. The residue was slurried DCM (15 mL) and water (15 mL) for 20 minutes. The solids were filtered, dried and purified by silica gel chromatography (methanol/DCM=0/100→15/85) to give the product. HPLC gave 23 mg of the title compound as a yellow solid. (12% yield). LC/MS (FA) ES+ 381. 1H NMR (300 MHz, DMSO-d6) δ: 8.72-8.60 (m, 2H), 8.41 (d, 1H, J=5.7 Hz), 7.88-7.85 (m, 2H), 7.40-7.36 (m, 2H), 7.32-7.28 (m, 2H), 6.58 (d, 1H, J=5.7 Hz), 4.80 (s, 2H).
Wird geladen…
