4,6-Dichloro-1,3,5-trazin-2-amine → 6-chloro-N-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[1,3,5]triazine-2,4-diamine

Participants

Reaction Steps

To an ice-cooled mixture of (5)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (226 mg, 0.69 mmol), 4,6-dichloro-[1,3,5]triazin-2-ylamine (125 mg, 0.76 mmol) and IPA (5 mL) was added DIPEA (0.59 mL, 3.45 mmol). The reaction mixture was stirred at RT (room temperature) for 64 h. The solvent was removed under reduced pressure and the resulting residue was partitioned between EtOAc and aqueous Na2CO3. The aqueous phase was extracted with EtOAc and the combined organic fractions washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, eluant EtOAc) affording the title compound as a colourless foam (quantitative). A portion (50 mg) was further purified by column chromatography (Si—PCC, eluant EtOAc) affording 269 after evaporation from acetone as a colourless foam (31.8 mg). LCMS (Method K): RT 4.06 min [M+H]+ 384.0/385.9. 1H NMR (DMSO-d6, 400 MHz, 80° C.): δ 7.69 (1H, bs), 7.66 (1H, dd, J=8.8, 4.9 Hz), 7.60-7.50 (5H, m), 7.07-7.02 (1H, m), 6.78 (2H, bs), 6.77 (1H, dd, J=8.9, 2.4 Hz), 5.21 (1H, quintet, J=7.1 Hz), 1.46 (3H, d, J=6.9 Hz)

Provenance & Evidence