Synthesis
The general procedure for the synthesis of 6-chloro-N4-methylpyrimidine-2,4-diamine from 2-amino-4,6-dichloropyrimidine and methylamine was as follows: first, 4,6-dichloropyrimidin-2-amine (3.28 g, 20.0 mmol), methylamine (12.0 mL, 24.0 mmol as a 2M methanol solution), and Hunig's base in n-butanol (20 mL) were The mixture was heated to 50 °C and then warmed to 95 °C for overnight reaction. After completion of the reaction, the mixture was concentrated and the crude product was dissolved in ethyl acetate (300 mL) and washed with water (3 x 150 mL). The organic layer was dried with magnesium sulfate, filtered and concentrated to afford the target product 6-chloro-N4-methylpyrimidine-2,4-diamine (2.90 g, 91% yield) as a light yellow solid.LCMS analysis showed the [M + H]+ peak as 159.
References
[1] Patent: WO2015/187089, 2015, A1. Location in patent: Page/Page column 70
[2] Patent: CN108191774, 2018, A. Location in patent: Paragraph 0203; 0204; 0205
[3] Patent: US6677345, 2004, B1. Location in patent: Page/Page column 12
[4] Patent: WO2010/120854, 2010, A1. Location in patent: Page/Page column 87
[5] Journal of Medicinal Chemistry, 2011, vol. 54, # 6, p. 1871 - 1895
