反应详情

温度

140 °C

The mixture of 3-(2-methanesulfonyl-pyrimidin-4-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine (from Example 46 supra) (150 mg, 0.402 mmol) and 4-chlorobenzylamine (228 mg, 1.608 mmol) was heated at 140° C. with stirring for 2 hours. The oil was purified by chromatography (silica gel, 10 g, 200˜300 mesh, eluting with dichloromethane:methanol, 30:1˜10:1) to afford the crude product (100 mg). The crude product was purified by prep-HPLC. Several drops of concentrated HCl were added to the fractions with product. After sonicating for several minutes, solution was concentrated under reduced pressure to afford (4-chloro-benzyl)-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine; hydrochloride. (Yield 38 mg, 21.8%). 1H NMR (300 MHz, CDCl3): δ 8.68 (s, 1H), 8.28 (s, 1H), 7.53 (d, 1H, J=6.9 Hz), 7.38-7.29 (m, 6H), 5.48-5.43 (m, 2H), 4.76 (brs, 2H), 3.68-3.61 (m, 4H), 3.34-3.27 (m, 4H), 2.89 (s, 3H). LC-MS: [M+H]+ 435.

1. customThe oil was purified by chromatography (silica gel, 10 g, 200˜300 mesh, eluting with dichloromethane:methanol, 30:1˜10:1)
2. customto afford the crude product (100 mg)
3. customThe crude product was purified by prep-HPLC
4. additionSeveral drops of concentrated HCl were added to the fractions with product
5. customAfter sonicating for several minutes
6. concentrationsolution was concentrated under reduced pressure