Cesium carbonate → 4-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)-9-methyl-8-((3-(1,1-dioxo-thiomorpholino)azetidin-1-yl)methyl)-9H-purin-6-yl)morpholine

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-8-[3-(1,1-Dioxo-1-thiomorpholin-4-yl)azetidin-1-ylmethyl]-9-methyl-6-morpholin-4-yl-9H-purine (125 mg, 0.27 mmol), 2-methylbenzimidazole (402 mg, 0.30 mmol), tris(dibenzylideneacetone)dipalladium (13 mg, 0.01 mmol), Xphos (13 mg, 0.02 mmol) and Cs2CO3 (179 mg, 0.55 mmol) in dioxane (4 mL) was purged with argon then heated at 145° C. for 30 min in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH/DCM then eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-15%) followed by an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH to give 355 as a cream solid (125 mg, 84%). LCMS (Method G): RT 4.73 min, [M+H]+ 552.2. 1H NMR (CDCl3, 400 MHz): δ 8.10-8.05 (m, 1 H); 7.73-7.67 (m, 1 H); 7.29-7.24 (m, 2 H); 4.35 (m, 4 H); 3.90-3.82 (m, 9 H); 3.59 (m, 2 H); 3.28 (m, 1 H); 3.11-3.04 (m, 6 H); 2.94 (s, 3 H) and 2.87-2.82 (m, 4 H)

Provenance & Evidence