General procedure for the synthesis of 4-(pyridin-4-yl)thiazol-2-amines from 4-(bromoacetyl)pyridine hydrobromide and thiourea:
Synthesis of batch 1: A mixture of 4-(bromoacetyl)pyridine hydrobromide (2.21 g, 7.90 mmol) and thiourea (0.60 g, 7.90 mmol) in anhydrous ethanol (10 mL) was subjected to stirring in a Biotage microwave reactor at 100°C for 30 min. After completion of the reaction, it was cooled to room temperature, the solid precipitate was collected by filtration and dried under vacuum.
Synthesis of batch 2: A mixture of 4-(bromoacetyl)pyridine hydrobromide (2.54 g, 9.06 mmol) and thiourea (0.69 g, 9.06 mmol) in anhydrous ethanol (10 mL) was placed in a Biotage microwave reactor and the reaction was stirred for 30 minutes at 100°C. The reaction was cooled to room temperature and the solid precipitate was collected by filtration. After completion of the reaction, it was cooled to room temperature, the solid precipitate was collected by filtration and dried under vacuum.
Synthesis of batch 3: A mixture of 4-(bromoacetyl)pyridine hydrobromide (2.16 g, 7.73 mmol) and thiourea (0.58 g, 7.73 mmol) in anhydrous ethanol (10 mL) was placed in a Biotage microwave reactor and the reaction was stirred for 30 minutes at 100°C. The reaction was cooled to room temperature and the solid precipitate was collected by filtration. After completion of the reaction, it was cooled to room temperature, the solid precipitate was collected by filtration and dried under vacuum.
The products of batches 1, 2 and 3 were combined and suspended in saturated aqueous sodium bicarbonate solution. Filtered, washed with sodium bicarbonate solution and dried under vacuum to afford the title compound 4-(pyridin-4-yl)thiazol-2-amine as a pale pink solid (5.53 g, 31.27 mmol, 95% yield).1H NMR (400 MHz, CD3OD) δ 8.49 (d, J = 6.3 Hz, 2H), 7.79 (d, J = 6.3 Hz, 2H) , 7.25 (s, 1H).
