2-Chloroquinazolin-4-amine

Synthesis

General procedure for the synthesis of 2-chloroquinazolin-4-amine using 2,4-dichloroquinazoline as starting material: 2,4-dichloroquinazoline (2.0 g, 10 mmol) was dissolved in tetrahydrofuran (THF, 10 mL), followed by addition of ammonia (28-30%, 18 mL). The reaction mixture was stirred at room temperature overnight. After completion of the reaction, the reaction mixture was diluted with ethyl acetate (EtOAc) and washed sequentially with saturated sodium bicarbonate (NaHCO3) solution, water and brine. The organic phase was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The resulting crude product was washed with ethyl acetate (EtOAc) to afford 2-chloroquinazolin-4-amine (1.3 g, 72% yield) as a white solid. The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 7.52-7.48 (m, 1H), 7.6-7.58 (m, 1H), 7.8-7.76 (m, 1H), 8.22-8.20 (m, 1H), 8.32 (bs, 2H).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 11, p. 1175 - 1179
[2] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569
[3] Patent: US2008/306053, 2008, A1. Location in patent: Page/Page column 65
[4] Journal of the American Chemical Society, 1948, vol. 70, p. 4264
[5] Journal of Medicinal Chemistry, 2008, vol. 51, # 24, p. 7855 - 7865