Synthesis
General procedure for the synthesis of 5-(2-chloropyridin-4-yl)-1,3,4-thiadiazol-2-amine (8.1.C) from the compound (CAS:474327-25-8): 42 g of polyphosphoric acid (PPA) was accurately weighed into a flask. After preheating the flask to 100 °C, 2.4 g (10 mmol) of intermediate 8.1.B was added in batches.After 1 h, the reaction mixture was diluted with ice water and the pH was adjusted with ammonia solution to 7. At this point, a bright yellow precipitate precipitated from the reaction solution. The precipitate was collected by filtration and washed. The precipitate was analyzed by LC/MS to confirm that the precipitate was the target product 8.1.C. 2.05 g of 8.1.C was finally obtained in 93% yield.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 19, p. 6218 - 6223
[2] Patent: WO2010/93849, 2010, A2. Location in patent: Page/Page column 50
[3] Patent: WO2013/109632, 2013, A2. Location in patent: Paragraph 0097
[4] Patent: US9303044, 2016, B2. Location in patent: Page/Page column 45
[5] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 4, p. 1148 - 1153
