p-Toluenesulfonic acid → HCID 86667338, compound

Participants

Reaction Conditions

Reaction Steps

To 4-(2-chloro-8-iodo-9-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-9H-purin-6-yl)morpholine (0.39 g, 0.8 mmol) in methanol (5 mL) was added p-toluenesulfonic acid (10 mg, 0.08 mmol). The reaction was heated at 50° C. for 30 min, whereupon precipitation was observed signaling reaction completion. This was confirmed by analytical LC-MS. The reaction mixture was concentrated in vacuo to give 3-(2-chloro-8-iodo-6-morpholino-9H-purin-9-yl)propan-1-ol. Copper(I) iodide (9 mg, 0.05 mmol), picolinic acid (10 mg, 0.09 mmol) and potassium phosphate (0.4 g, 1.9 mmol) were combined in oven-dried 50-mL round-bottom flask and evacuated/recycled with N2 atmosphere. Subsequently, 3-(2-chloro-8-iodo-6-morpholino-9H-purin-9-yl)propan-1-ol was dissolved in anhydrous dimethyl sulfoxide (6.7 mL) and introduced via syringe. The entire mixture was heated at 80° C. for 20 h. LC-MS indicated good conversion to the desired product. The reaction mixture was cooled to room temperature, diluted with water and EtOAc, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by FCC (40 g silica gel column, 0-100% EtOAc in heptane) to give 112 mg of 2-chloro-4-morpholino-8,9-dihydro-7H-[1,3]oxazino[2,3-e]purine (40%). MS (ESI+): m/z 296.2 (M+H+)

Provenance & Evidence