Reaction Steps
A solution of the 4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butanal (367 mg, 0.87 mmol), 7-[(3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (300 mg, 0.87 mmol) and MgSO4 (1.05 g, 8.74 mmol) in DCE (10 ml) was stirred at RT for 15 min. Na(AcO)3BH (259 mg, 1.22 mmol) was then added to the reaction mixture and stirred for 1 hour. Sat. NaHCO3 (20 ml) was added to the reaction mixture and stirred for 5 mins. Brine (10 ml) was added to the reaction mixture, and the product was extracted with DCM (2×30 ml), the combined extracts were dried over Na2SO4, filtered and concentrated. Purification by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:199-3:97) gave the desired product as a pink foamy solid. The mixed fractions were combined and purified on a preparative TLC plate eluting with 7N NH3 in MeOH:DCM (2×4:96) to give an off white solid (270 mg, 41%): MS (ESI+) for C36H49ClF3N7O3Si m/z 748.25 [M+H]+; HPLC purity>95% (ret. time, 1.75 min); 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.14-8.47 (1H, m), 7.78-8.11 (1H, m), 7.40-7.78 (1H, m), 6.99 (1H, d, J=3.63 Hz), 6.63 (1H, br. s.), 5.34-5.69 (3H, m), 4.81-5.11 (2H, m), 4.53 (1H, t, J=6.15 Hz), 3.33-3.71 (2H, m), 2.89-3.14 (3H, m), 2.77-2.90 (1H, m), 2.68-2.79 (3H, m), 2.25-2.49 (2H, m), 2.15 (1H, q, J=11.87 Hz), 1.89-2.06 (2H, m), 1.63-1.71 (2H, m), 1.51-1.61 (3H, m), 1.21-1.37 (3H, m), 0.84-1.00 (4H, m), 0.62-0.78 (2H, m), −0.15-0.06 (9H, m).
