18903-18-9

1759-25-7

18903-18-9

Synthesis of compound 16c: Preparation of ethyl 5-aminothiazole-4-carboxylate: compound 16b (9.0 g, 58 mmol) was suspended in toluene (200 ml). Lawesson's reagent (23.0 g, 58 mmol, 1 eq.) was added at once. The resulting yellow suspension was stirred overnight at 70 °C and under N2 atmosphere. Upon completion of the reaction, the mixture was cooled to 0°C and the toluene layer was poured from the colloidal material at the bottom of the flask and washed with aqueous 1N hydrochloric acid (6 x 50 ml). The colloidal material was dissolved in methanol (150 ml) and subsequently concentrated under reduced pressure. The residue (brown oily substance) was suspended in tert-butyl methyl ether (TBME, 300 ml) and washed with 1N aqueous hydrochloric acid (1 x 300 ml, 2 x 100 ml). The aqueous portions were combined and alkalized with 2N aqueous sodium hydroxide (460 ml) followed by extraction with ethyl acetate (EtOAc, 1 x 300 ml, 2 x 200 ml and 1 x 100 ml). The organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give the crude product ethyl 5-aminothiazole-4-carboxylate (7 g). The crude product was purified by column chromatography (silica gel, heptane-ethyl acetate, 1/1) to afford compound 16c (6 g, 35 mmol, 60% yield) as a brown solid.1H-NMR (300 MHz, CDCl3) δ 7.89 (s, 1H), 6.04 (bs, 2H), 4.42 (q, 2H, J=7Hz), 1.43 (t, 3H) J=7Hz).