2-allyl-6-(Methylthio)-1H-pyrazolo[3,4-d]pyriMidin-3(2H)-one

5909-24-0

21075-86-5

955368-90-8

The general procedure for the synthesis of 2-allyl-6-(methylmercapto)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one from ethyl 4-chloro-2-methylthio-pyrimidine-5-carboxylate and tert-butyl 1-allylhydrazinecarboxylate was as follows: to a THF solution (150 ml) of ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (11.1 g, 47.8 mmol) DIPEA (20.8 ml, 120 mmol) and tert-butyl 1-allylhydrazinecarboxylate (8.23 g, 47.8 mmol) were added. The reaction mixture was heated to reflux for 72 hours followed by vacuum concentration. Ether (50 ml) was added to the residue and the precipitate was collected by filtration. The filtrate was evaporated to dryness and the residue was cooled in an ice bath before adding trifluoroacetic acid (40 ml). The resulting solution was stirred at room temperature for 1 hour and then continued at 70°C for 1 hour. After the solvent was removed by vacuum, the residue was dissolved in ethanol (50 ml), cooled in an ice bath and 6M sodium hydroxide solution (75 ml) was added. After stirring for 15 minutes at room temperature, it was acidified by adding concentrated hydrochloric acid (40 ml). The orange solution was evaporated to dryness and the residue was partitioned between chloroform (100 ml) and water (100 ml). The organic phase was washed with brine (50 ml), dried over magnesium sulfate and concentrated under vacuum and ground with hexane. The solid precipitate was washed with ethanol and ether and dried under vacuum to give 2-allyl-6-(methylmercapto)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one as a yellow solid (5.44 g, 24.5 mmol, 51% yield). Thin-layer chromatography Rf value was 0.45 (dichloromethane:methanol=9:1); melting point was 125-128 °C; IR spectra (cm^-1) 3032, 2979, 2926, 2659, 1656, 1615, 1561, 1154; 1H NMR (400 MHz, DMSO-d6) δ 2.53 (3H, s, -SCH3), and 4.38 (2H, d, J=5.2 Hz, N2-CH2), 5.06-5.20 (2H, m, allyl C-H cis/trans), 5.87 (1H, ddt, J=17.2, 10.5, 5.3 Hz, olefin CH), 8.67 (1H, s, H-4), 12.65 (1H, s, NH); mass spectrum [M+H ]+ m/z 223.1.