反应详情

温度

110 °C

A mixture of 2-{1-[2-chloro-9-methyl-6-((R)-3-methylmorpholin-4-yl)-9H-purin-8-ylmethyl]piperidin-4-yl}propan-2-ol (120 mg, 0.28 mmol), 2-ethylbenzimidazole (46 mg, 0.31 mmol), tris(dibenzylideneacetone)dipalladium (7 mg, 2.5 mol %), XPhos (14 mg, 10 mol %) and Cs2CO3 (139 mg, 0.43 mmol) in dioxane (3 mL) was purged with argon then heated at 110° C. for 4 h in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH/DCM. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%) followed by (Si—PCC, MeOH:DCM, 0-10%) affording 781 as a white solid (65 mg, 43%). LCMS (method I): RT 2.64 min, [M+H]+ 533.3. 1H NMR (CDCl3, 400 MHz): δ 8.03-8.02 (1 H, m), 7.76-7.75 (1 H, m), 7.30-7.25 (2 H, m), 4.06-4.05 (1 H, m), 3.88 (3 H, s), 3.83 (2 H, s), 3.73 (2 H, s), 3.70-3.55 (2 H, m), 3.36 (2 H, q, J=7.48 Hz), 2.99-2.96 (2 H, m), 2.16-2.06 (2 H, m), 1.81-1.71 (2 H, m), 1.58 (2 H, brd s), 1.48-1.42 (6 H, m), 1.43-1.27 (3 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/DCM
4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)