Reaction Steps
4-(5,6-Dichloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)butanal (0.310 g, 0.801 mmol) and 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 (0.262 g, 0.763 mmol) were dissolved in DCE (17 ml) at r.t. under N2 and left for 15 mins. Sodium triacetoxyborohydride (0.226 g, 1.07 mmol) was added and the reaction left overnight. The reaction was quenched by the addition of sat. Na2CO3 solution (20 ml) and DCM (20 ml). The organic layer was separated and the aqueous layer was extracted with DCM (3×20 ml). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give the crude product. The product was purified by silica flash column chromatography using between 100% DCM to 10% MeOH:90% DCM as eluent to give the product as a white foam (0.222 g, 41%): MS (ESI+) for C35H49Cl2N7O3Si m/z 714.4 [M+H]+; LC purity 99% (ret. time, 1.73 min); 1H NMR (500 MHz, CDCl3) δ 8.28 (s, 1H), 7.80 (s, 1H), 7.51 (s, 1H), 7.00 (d, J=3.63 Hz, 1H), 6.64 (br. s., 1H), 5.62 (br. s., 1H), 5.42 (s, 2H), 4.91-5.03 (m, 2H), 4.55 (t, J=6.23 Hz, 1H), 3.45-3.59 (m, 2H), 2.90-3.02 (m, 3H), 2.82-2.89 (m, 1H), 2.69-2.81 (m, 3H), 2.45 (dt, J=12.61, 6.46 Hz, 1H), 2.35 (tt, J=12.41, 6.27 Hz, 1H), 2.16 (q, J=11.98 Hz, 1H), 1.97 (dt, J=15.41, 7.66 Hz, 2H), 1.69 (quin, J=7.37 Hz, 2H), 1.57 (s, 3H), 1.30 (s, 3H), 0.85-0.99 (m, 4H), 0.64-0.76 (m, 2H), −0.03 (s, 9H).
