反应详情

温度

80 °C

A mixture of (S)-1-[6-fluoro-1-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]ethylamine, (0.055 g, 0.21 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.070 g, 0.30 mmol) and DIPEA (0.07 mL, 0.38 mmol) in IPA (1.5 mL) was stirred at 80° C. in a sealed tube for 16 h. After cooling, the reaction mixture was concentrated in vacuo and the residue purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM). The product was dissolved in methanol (4 mL) and treated with HCl/dioxane (4M, 0.5 mL, 2.0 mmol) then stirred for 15 minutes. The resulting mixture was concentrated in vacuo and the residue loaded onto an Isolute® SCX-2 cartridge and washed with MeOH then the product eluted with 2M NH3/MeOH and concentrated in vacuo to give 419 as a white solid (0.050 g, 63%). LCMS (Method K): RT 2.65 min [M+H]+ 378.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.90 (1H, s), 8.22-8.03 (3H, m), 7.89-7.81 (1H, m), 7.76 (1H, s), 7.66-7.62 (1H, m), 7.09-7.05 (1H, m), 7.00-6.91 (1H, m), 5.61-5.42 (1H, m), 3.86 (3H, s), 1.57 (3H, d, J=6.84 Hz)

1. temperatureAfter cooling
2. concentrationthe reaction mixture was concentrated in vacuo
3. customthe residue purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM)
4. dissolutionThe product was dissolved in methanol (4 mL)
5. stirringthen stirred for 15 minutes
6. concentrationThe resulting mixture was concentrated in vacuo
7. washwashed with MeOH
8. washthe product eluted with 2M NH3/MeOH
9. concentrationconcentrated in vacuo