反应详情

温度

150 °C

A mixture of 2-{1-[2-chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purin-8-ylmethyl]piperidin-4-yl}propan-2-ol (200 mg, 0.47 mmol), 2-ethylbenzimidazole (73 mg, 0.50 mmol), tris(dibenzylideneacetone)dipalladium (12 mg, 2.5 mol %), XPhos (20 mg, 10 mol %) and Cs2CO3 (218 mg, 0.67 mmol) in DMF (6 mL) was purged with argon then heated at 150° C. for 1 h in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-5%) then (Si-PCC, MeOH:DCM, 0-3%) affording 775 (95 mg, 38%). LCMS (method I): RT 2.65 min, [M+H]+ 533.3. 1H NMR (CDCl3, 400 MHz): δ 8.03-8.02 (1 H, m), 7.75-7.74 (1 H, m), 7.27-7.24 (2 H, m), 5.40 (2 H, brd s), 4.09-4.03 (1 H, m), 3.88 (3 H, s), 3.83 (2 H, s), 3.75-3.55 (4 H, m), 3.36 (2 H, q, J=7.48 Hz), 2.98-2.95 (2 H, m), 2.11 (2 H, t, J=10.92 Hz), 1.81-1.71 (2 H, m), 1.45-1.44 (6 H, m), 1.34-1.31 (4 H, m), 1.19 (6 H, s)

1. customwas purged with argon
2. washwas washed with MeOH
3. washthe product eluted with 2M NH3/MeOH
4. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-5%)