p-Toluenesulfonic acid → 4-(6-bromo-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-N-(2-amino-5-bromophenyl)pyrimidine-2,4-diamine (750 mg, 2.68 mmol) in mixture of methanol (7 mL) and THF (30 mL) was added trimethyl orthoformate (8.81 ml, 80.32 mmol) and TsOH (0.04 ml, 0.27 mmol). The reaction mixture was stirred at 70° C. for 1 h. Then another portion of trimethyl orthoformate (4.4 ml, 40.16 mmol) was added. Stirring at 70° C. was continued for another 6 hr. The reaction mixture was allowed to cool down to RT then a saturated aqueous solution of NaHCO3 was added. The product was extracted into DCM (×3) and the combined organic layers were washed with brine and dried over Na2SO4, filtered and concentrated in vacuo to give the title compound; 1H NMR (500 MHz, DMSO) δ 7.08-7.24 (3H, m), 7.50 (1H, dd, J=8.51, 1.89 Hz), 7.71 (1H, d, J=8.51 Hz), 8.37 (1H, d, J=5.52 Hz), 8.83 (1H, d, J=1.73 Hz), 9.08 (1 H, s); LC-MS (Method B): m/z=+289.9, 291.8 (M+H)+. This compound, with LC-MS purity=70%, was used in the next step without further purification.

Provenance & Evidence