Synthesis
Step 1: Synthesis of 2-chloro-4-methyl-6-(methylthio)pyrimidine. 2,4-Dichloro-6-methylpyrimidine (20.0 g, 0.123 mol) was dissolved in tetrahydrofuran (THF, 200 mL). Sodium methanethiol (20% aqueous solution, 43 g, 0.129 mol) was added slowly and dropwise at -5 °C. After the dropwise addition was completed, the reaction mixture was stirred at room temperature overnight. After completion of the reaction, water (100 mL) and ethyl acetate (EtOAc, 100 mL) were added for extraction and the organic layer was separated. The organic layer was washed twice with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a yellow solid. The solid was washed with petroleum ether (PE, 100 mL) to afford the target product 2-chloro-4-methyl-6-(methylthio)pyrimidine (9.1 g). Mass spectrometry (electrospray positive ion mode, ES+) analysis: the theoretical molecular weight of C6H7ClN2S was 174 and the measured value was 175 [M+H]+.
References
[1] Organic Letters, 2016, vol. 18, # 9, p. 2180 - 2183
[2] Patent: WO2015/57945, 2015, A1. Location in patent: Paragraph 00127
[3] Patent: WO2016/168619, 2016, A1. Location in patent: Paragraph 00178
[4] Patent: WO2017/79140, 2017, A1. Location in patent: Page/Page column 49
[5] Patent: WO2017/210545, 2017, A1. Location in patent: Paragraph 00181; 00182
