171178-46-4

124-38-9

171178-45-3

171178-46-4

Step (c): Synthesis of 5-tert-butoxycarbonylamino-2-chloropyridine-4-carboxylic acid Tert-butyl 6-chloropyridin-3-ylcarbamate (800 mL ether suspension) was mixed with TMEDA and cooled to -75 °C. A hexane solution of 1.6 M n-butyllithium was slowly added dropwise at a temperature below -65 °C. After the dropwise addition was completed, the reaction mixture was warmed to -15°C to -10°C and stirred in this temperature range for 2 hours. Subsequently, the mixture was cooled again to -75°C and dry carbon dioxide gas was passed into it for 3 hours. Afterwards, the reaction mixture was allowed to slowly warm up to room temperature overnight, during which time carbon dioxide was continuously passed through. Upon completion of the reaction, the reaction was carefully quenched with 20% aqueous ammonium hydroxide solution (1.8 L) and the aqueous phase was extracted with ether. The reaction was then acidified to pH 5 with 50% aqueous hydrochloric acid, the resulting solid was collected by filtration, washed with water and dried to afford 33.07 g (69.3% yield) of 5-tert-butoxycarbonylamino-2-chloropyridine-4-carboxylic acid as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.5 (s, 9H), 7.7 (s, 1H), 9.1 (s, 1H), 10.0 (s, 1H). MS (APCI) m/z: [M + 1]+ = 273.1.