反应详情

温度

85 °C

A mixture of (S)-1-(7-Bromo-6-fluoro-1-methyl-1H-benzoimidazol-2-yl)ethylamine, (0.50 g, 1.84 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.61 g, 2.57 mmol) and DIPEA (0.60 mL, 3.31 mmol) in IPA (7 mL) was stirred at 85° C. in a sealed tube for 21 h. After cooling, the was mixture partitioned between DCM (3×) and saturated aqueous NaHCO3. The combined DCM extracts were dried (Na2SO4), concentrated in vacuo and the residue purified by chromatography (SiO2, 0-5% (2M ammonia in methanol) in DCM). The product was dissolved in methanol (15 mL), treated with HCl/dioxane (4M, 2.0 mL, 8.0 mmol) then stirred for 10 minutes. The reaction mixture was concentrated in vacuo and the residue loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH then concentrated in vacuo to give 430 as a white solid (0.45 g, 63%). LCMS (Method K): RT 3.12 min [M+H]+ 390.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.99 (1H, s), 8.27-7.97 (3H, m), 7.62 (1H, dd, J=8.72, 4.66 Hz), 7.23-7.16 (1H, m), 5.76 (1H, m), 4.09 (3H, s), 1.67 (3H, d, J=6.76 Hz). Signals split due to presence of tautomers

1. temperatureAfter cooling
2. customthe was mixture partitioned between DCM (3×) and saturated aqueous NaHCO3
3. dry with materialThe combined DCM extracts were dried (Na2SO4)
4. concentrationconcentrated in vacuo
5. customthe residue purified by chromatography (SiO2, 0-5% (2M ammonia in methanol) in DCM)
6. dissolutionThe product was dissolved in methanol (15 mL)
7. stirringthen stirred for 10 minutes
8. concentrationThe reaction mixture was concentrated in vacuo
9. washwas washed with MeOH
10. washthe product eluted with 2M NH3/MeOH
11. concentrationthen concentrated in vacuo