反应详情

温度

115 °C

A mixture of 4-[1-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)azetidin-3-yl]piperazin-2-one (315 mg, 0.74 mmol), 2-ethylbenzimidazole (120 mg, 0.82 mmol), tris(dibenzylideneacetone)dipalladium (17 mg, 0.02 mmol), XPhos (35 mg, 0.07 mmol) and Cs2CO3 (365 mg, 1.12 mmol) in dioxane (10 mL) was purged with argon then heated at 115° C. for 4 h then stirred at r.t. for 16 h. The reaction mixture was filtered through Celite®, washing with dioxane, and the filtrate concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 1-10%) affording 796 (146 mg, 37%). LCMS (method G): RT 4.90 min, [M+H]+ 534.3. 1H NMR (DMSO, 400 MHz): δ 7.99-7.99 (1 H, m), 7.75 (1 H, s), 7.64-7.63 (1 H, m), 7.26-7.25 (2 H, m), 4.32 (4 H, brd s), 4.04 (2 H, s), 3.79 (4 H, t, J=4.61 Hz), 3.57-3.52 (2 H, m), 3.31 (2 H, s), 3.25 (2 H, q, J=7.43 Hz), 3.18-3.14 (5 H, m), 2.87 (2 H, s), 1.32 (3 H, t, J=7.42 Hz)

1. customwas purged with argon
2. filtrationThe reaction mixture was filtered through Celite®
3. washwashing with dioxane
4. concentrationthe filtrate concentrated in vacuo
5. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 1-10%)