Acetonitrile → 1-(4-(tert-butyl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)propyl)urea

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-(3-(4-(tert-butyl)phenyl)ureido)propyl methanesulfonate (224 mg, 0.682 mmol), tetra-n-butylammonium iodide (252 mg, 0.682 mmol) and N,N-diisopropylethylamine (120 μL, 0.67 mmol) was treated with N-(2,4-dimethoxybenzyl)-7-((3aR,4R,6R,6aR)-2,2-dimethyl-6-((methylamino)methyl)tetrahydrofuro[3,4-d][1,3]-dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (320 mg, 0.68 mmol) in acetonitrile (7.8 mL, 150 mmol) and the solution was heated at 65° C. After 16.5 h at 65° C., HPLC indicated the reaction was about 78-85% complete. An additional 60 mg of mesylate (in 0.4 mL CH3CN) and 67 mg of TBAI were added and continued heating for 7 h. The reaction mixture was cooled to room temperature and concentrated. The crude residue was purified by flash chromatography (60 g silica gel, 3-7% 7N NH3 in CH3OH/CH2Cl2) to yield the product contaminated with TBAI. The material was dissolved in 20 mL 1/1 ethyl acetate/ethyl ether and washed with three 10 mL portions of H2O. The organic phase was dried over Na2SO4, filtered and concentrated to yield the title compound (295 mg, 62%) as a foam: MS (ESI+) for C38H51N7O6 m/z 702.2 (M+H)+: (ESI−) for C38H51N7O6 m/z 700.3 (M−H)−; HPLC purity 96% (ret. time, 3.69 min).

Provenance & Evidence