Reaction Steps
Formaldehyde (36 μl, 0.49 mmol, 37%(aq)) was added to a solution of 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-({[(3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl]amino}methyl)-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine in MeOH (5 ml) and THF (5 ml), and the reaction was stirred at RT for 30 mins. NaCNBH3 (18 mg, 0.29 mmol) was added portionwise, and the reaction stirred for a further 2 hours at RT after which LC MS showed the reaction to be complete. The reaction mixture was concentrated under in vacuo, and the residue partitioned between water (20 ml) and DCM (20 ml) and the layers were separated. The aqueous layer was extracted with DCM (2×20 ml), the combined organics were then dried over Na2SO4, and concentrated. Purification by prep. TLC, eluting with 7N NH3 in MeOH:DCM (5:95) gave the desired product (114 mg, 66%) as a colourless oil; MS (ESI+) for C36H50F3N7O3Si m/z 714.45 [M+H]+; HPLC purity 100% (ret. time, 1.77 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm −0.14-0.05 (9 H, m), 0.85-0.99 (2 H, m), 1.18-1.35 (3 H, m), 1.37-1.53 (2 H, m), 1.52-1.64 (3 H, m), 1.89-2.15 (3 H, m), 2.18-2.28 (2 H, m), 2.29-2.70 (6 H, m), 2.72-2.96 (1 H, m), 2.97-3.20 (2 H, m), 3.48 (3 H, s), 3.50-3.58 (2 H, m), 4.37-4.58 (1 H, m), 4.85-5.05 (2 H, m), 5.11-5.38 (2 H, m), 5.41-5.57 (2 H, m), 6.35 (1 H, d, J=3.63 Hz), 6.84-7.19 (1 H, m), 7.50 (1 H, d, J=8.35 Hz), 7.68 (1 H, s), 7.78 (1 H, d, J=8.35 Hz), 8.13-8.52 (1 H, m)
