反应详情

温度

145 °C

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-(3-morpholin-4-yl-azetidin-1-ylmethyl)-9H-purine (83 mg, 0.20 mmol), 2-cyclopropylbenzimidazole (39 mg, 0.24 mmol), tris(dibenzylideneacetone)dipalladium (9 mg, 0.01 mmol), Xphos (19 mg, 0.04 mmol) and Cs2CO3 (133 mg, 0.41 mmol) in dioxane (2 mL) was purged with argon then heated at 145° C. for 30 min in a microwave reactor. The reaction mixture was filtered through a pad of celite, washing with EtOAc. The filtrate was concentrated in vacuo and purified by column chromatography (Si—PCC, MeOH:DCM, 0-20%) affording 548 as a beige foam (92 mg, 87%). LCMS (Method I): RT 2.52 min, [M+H]+ 530.3. 1H NMR (CDCl3, 400 MHz): δ 7.95-7.91 (m, 1 H); 7.69-7.65 (m, 1 H); 7.27-7.18 (m, 2 H); 4.36 (m, 4 H); 3.93 (s, 2 H); 3.89-3.83 (m, 7 H); 3.75 (m, 4 H); 3.65 (m, 2 H); 3.24 (m, 2 H); 3.13 (m, 1 H); 2.89-2.81 (m, 1 H); 2.39 (m, 4 H); 1.37-1.32 (m, 2 H) and 1.08-1.02 (m, 2 H)

1. customwas purged with argon
2. filtrationThe reaction mixture was filtered through a pad of celite
3. washwashing with EtOAc
4. concentrationThe filtrate was concentrated in vacuo
5. custompurified by column chromatography (Si—PCC, MeOH:DCM, 0-20%)