Cesium carbonate → 5-(2-Chloro-5-methylpyrimidin-4-ylthio)pyrimidine-2-carbonitrile

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Reaction Conditions

Reaction Steps

A mixture of 4-bromo-2-cyanopyrimidine (280 mg, 1.52 mmol), Pd[PPh3]4 (86 mg, 0.074 mmol) and Cs2CO3 (628 mg, 1.93 mmol) was evacuated and purged with nitrogen. Toluene (15 mL) was then added followed by TIPS-SH (413 μL, 1.92 mmol). The mixture was heated at 100° C. for 22 h and the resulting orange suspension was then cooled to 0° C. 2,4-Dichloro-5-methylpyrimidine (267 μL, 2.28 mmol) was then added followed by tetrabutyl ammonium fluoride (1.0 M in THF, 3.8 mL, 3.8 mmol) dropwise. The mixture was stirred at 0° C. for 30 min then allowed to warm to room temperature and stirred for 6 h. The reaction was quenched with saturated aqueous NH4Cl and the mixture was extracted three times with EtOAc. The combined extracts were washed with water, brine then dried (Na2SO4). Solvent removal under reduced pressure and purification by silica gel chromatography with 100% dichloromethane then 1% EtOAc/dichloromethane as eluent gave 5-(2-chloro-5-methylpyrimidin-4-ylthio)pyrimidine-2-carbonitrile (327 mg, 82%) as a pale yellow solid: 1H NMR (300 MHz, CDCl3): δ 8.97 (s, 2H), 8.25 (s, 1H), 2.35 (s, 3H); Std LC-MS; rt 6.30 min; m/z 264.1 [M+H]+; purity 96% at 254 nm.

Provenance & Evidence