Reaction Steps
7-((3aR,4R,6R,6aR)-6-(((3-((5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)methyl)cyclobutyl)(methyl)amino)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (170 mg, 0.24 mmol) was dissolved in a mixture of trifluoroacetic acid (5.0 mL) and water (0.5 mL) which had been precooled at 0° C. in an ice bath. The solution was stirred at 0° C. for 30 minutes, and warmed to room temperature. After 5 h at room temperature, the now very pink reaction mixture was concentrated. The residue was taken up in 10 mL MeOH and concentrated. This procedure was repeated twice and the residue placed on high vac for 1 h. The material was taken up in 7 mL MeOH and was treated with 130 mg K2CO3 and five drops of water. The mixture was allowed to stir for 1 hr, during which time the solution was found to be basic. The mixture was filtered through a fine frit, the solids were washed with 10 mL MeOH and the filtrate was concentrated to yield a nearly colorless solid. The crude material was purified by flash chromatography (30 g silica gel; 12% 7N NH3 in CH3OH/CH2Cl2) to yield Compound 6 (81 mg, 65%) as a colorless glass/stiff foam: MS (ESI+) for C28H37N7O3 m/z 520.4 (M+H)+; MS (ESI−) for C28H37N7O3 m/z 518.5 (M−H)−; HPLC purity >95% (ret. time, 2.51 min); 1H NMR (400 MHz, d4-MeOH) δH ppm 8.08 (s, 1H), 7.48 (br. s., 1H), 7.39 (d, J=8.50 Hz, 1H), 7.29 (dd, J=8.40, 4.87 Hz, 1H), 6.63 (m, 1H), 6.12 (d, J=4.15 Hz, 1H), 4.40 (m, 1H), 4.09 (m, 2H), 3.15 (m, 0.5H), 3.02 (d, J=8.09 Hz, 1H), 2.92 (d, J=7.26 Hz, 1H), 2.84 (m, 0.5H), 2.65 (m, 2H), 2.43 (m, 1H), 2.29 (m, 1H), 2.20 (d, J=5.80 Hz, 3H), 2.13 (m, 1H), 1.99 (br. s., 1H), 1.67 (m, 1H), 1.37 (d, J=3.94 Hz, 9H), 1.30 (dd, J=13.99, 4.66 Hz, 1H).
