Synthesis
General procedure for the synthesis of 4-amino-6-chloro-2-(methylthio)pyrimidine from 4,6-dichloro-2-(methylthio)pyrimidine:
1. 4,6-Dichloro-2-(methylthio)pyrimidine was added slowly in a 2L autoclave with THF and ammonia.
2. The reaction mixture was heated to 50-60°C and kept at that temperature for 3-4 hours (pressure in the reactor was maintained at 7-8 Kg/cm2).
3. The progress of the reaction was monitored by TLC.
4. After completion of the reaction, the reaction mixture was cooled to 25-35°C. 5.
5. Concentrate the reaction mixture under vacuum. 6.
6. Hexane was added and stirred at 25-35 °C for 30-45 min.
7. Collect the solid product by filtration and wash with hexane.
8. Wash the solid product with water (2 x 400 mL).
9. Dry the solid product at 25-35 °C until the moisture content (MC) is less than 2%.
Yield: 352.0 g. Yield: 97.77%.
HPLC purity: 99.07%.
Note: For different analogs, other suitable conditions may be used, such as the use of methanol or dioxane solutions of ammonia.
Example 1-2: Preparation of 4-amino-6-chloro-2-methylthiopyrimidine, step 6.1.
References
[1] Patent: WO2011/97594, 2011, A2. Location in patent: Page/Page column 100-101
[2] Chemistry - A European Journal, 1999, vol. 5, # 12, p. 3450 - 3458
[3] Patent: WO2007/141571, 2007, A2. Location in patent: Page/Page column 25
[4] American Chemical Journal, 1904, vol. 32, p. 353
[5] Patent: US2005/288502, 2005, A1. Location in patent: Page/Page column 20
