[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[S:10][C:9]([C:11](O)=[O:12])=[CH:8][C:7]=1[CH3:14].C1C=CC2N(O)[N:22]=[N:21]C=2C=1.C(Cl)CCl.O.NN>C(O)(C)C.CN(C=O)C>[NH3:21].[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[S:10][C:9]([C:11]([NH:21][NH2:22])=[O:12])=[CH:8][C:7]=1[CH3:14]A suspension of 5-formyl-4-methyl-thiophene-2-carboxylic acid (3.00 g, 17.6 mmol), ethylene glycol (3.28 g, 52.9 mmol) and p-toluene sulfonic acid hydrate (61 mg, 0.353 mmol) in toluene (80 mL) is refluxed for 3 h in a Dean-Stark apparatus. The clear solution is diluted with EA and washed twice with water. The washings are extracted back with EA. The combined organic extracts are dried over Na2SO4, filtered, concentrated and dried to give 5-[1,3]dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid (3.69 g) as a pale yellow resin, LC-MS: tR=0.46 min, [M+1]+=215.15. b) To a mixture of 5-[1,3]dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid (3.00 g, 14.0 mmol), HOBt (2.52 g, 16.8 mmol) and EDC (2.95 g, 15.4 mmol) in isopropanol (240 mL), hydrazine hydrate (1.50 g, 29.4 mmol) is added at 0° C. The suspension is stirred at 0° C., diluted with DMF and warmed to rt. Stirring is continued at rt for 2 h before the solvent is evaporated. The residue is dissolved in acetonitrile and separated by prep. HPLC (XBridge C18, 50×50 +100×50 mm, 10 μm, gradient of acetonitrile in water containing 0.5% of aq. ammonia) to give the title compound (2.43 g) as a colourless solid; LC-MS: tR=0.57 min, [M+1]+=228.96; 1H NMR (D6-DMSO): δ2.20 (s, 3H), 3.90-3.99 (m, 2H), 3.99-4.08 (m, 2H), 4.43 (s, 2H), 6.06 (s, 1H), 7.43 (s, 1H), 9.69 (s, 1H).
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