反应详情

温度

90 °C

A mixture of (S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (100 mg, 0.31 mmol), 4-chloro-6-methyl-[1,3,5]triazin-2-ylamine (48.4 mg, 0.34 mmol) and DIPEA (0.26 mL, 1.52 mmol) in n-butanol (2 mL) was stirred at 90° C. in a sealed vial for 16 h. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (C18, gradient 20-45% MeOH in 0.5% TFA/H2O) then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH affording 258 as a white solid (94.2 mg, 85%). LCMS (Method K): RT 3.04 min [M+H]+ 364.1. 1H NMR (DMSO-d6, 400 MHz, 80° C.): δ 7.65 (1H, dd, J=8.7, 4.8 Hz), 7.61-7.57 (2H, m), 7.55-7.51 (3H, m), 7.04 (1H, ddd, J=9.8, 8.7, 2.5 Hz), 6.91 (1H, bs), 6.77 (1H, dd, J=9.0, 2.5 Hz), 6.13 (2H, bs), 5.26 (1H, quintet, J=7.3 Hz), 2.02 (3H, s), 1.44 (3H, d, J=6.9 Hz)

1. temperatureAfter cooling to RT
2. customvolatiles were removed under reduced pressure
3. customthe resulting residue purified by column chromatography (C18, gradient 20-45% MeOH in 0.5% TFA/H2O)
4. washThe cartridge was washed with MeOH
5. washthe product eluted with 0.5M NH3/MeOH affording 258 as a white solid (94.2 mg, 85%)
6. customRT 3.04 min [M+H]+ 364.1