4-Amino-5-bromo-2-chloropyrimidine

Uses

4-Amino-5-bromo-2-chloropyrimidine is a useful research chemical, an intermediate in the synthesis of pyrimidine Schiff bases with antibacterial, antioxidant, anti-inflammatory and antifungal properties.

Uses

4-Amino-5-bromo-2-chloropyrimidine is an important raw material and intermediate used in organic synthesis, pharmaceuticals and agrochemicals.

Synthesis

1. Dissolve 5-bromo-2,4-dichloropyrimidine in a solvent mixture of N-hydroxysuccinimide (NHS)/methanol (MEOH) and stir the reaction at room temperature. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The resulting solid was washed with deionized water (H2O) and dried in vacuum to obtain a white solid 5-bromo-2-chloropyrimidin-4-amine in quantitative yield. 2. The above white solid was dissolved in a mixed solvent of dimethyl sulfoxide (DMSO)/water (H2O). To the solution was added 1,4-diazabicyclo[2.2.2]octane (DABCO) and sodium cyanide (NaCN), and the reaction mixture was heated to 60 °C for the reaction. After completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate (AcOEt). The organic phases were combined and dried with anhydrous sodium sulfate (Na2SO4). Purification by silica gel column chromatography with ethyl acetate-hexane as eluent afforded 4-amino-5-bromopyrimidine-2-carbonitrile as a white solid. 3. The above product was dissolved in N,N-dimethylformamide (DMF) under the protection of nitrogen (N2) and 1-chloro-4-prop-2-ynylbenzene, (PPh3)2PdCl2 and cuprous iodide (CuI) were added. The reaction mixture was stirred at 80°C for the reaction. After completion of the reaction, the reaction was quenched by addition of saturated aqueous ammonium chloride (NH4Cl) and stirring was continued for 1 hour. The mixture was extracted twice with ethyl acetate (AcOEt). The organic phases were combined, washed with aqueous sodium bicarbonate (NaHCO3) and dried over anhydrous sodium sulfate (Na2SO4). The target product 4-amino-5-bromo-2-chloropyrimidine was purified by silica gel fast column chromatography using ethyl acetate-hexane as eluent.

References

[1] Patent: WO2004/69256, 2004, A1. Location in patent: Page/Page column 35
[2] Patent: WO2011/112766, 2011, A2. Location in patent: Page/Page column 125; 126
[3] Patent: WO2015/155042, 2015, A1. Location in patent: Page/Page column 24
[4] Patent: WO2016/166255, 2016, A1. Location in patent: Page/Page column 29
[5] Tetrahedron Letters, 2001, vol. 42, # 6, p. 999 - 1001