Sulfuric acid magnesium salt (1:1) → 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-{[propan-2-yl({4-[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butyl})amino]methyl}-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Participants

Reaction Steps

A solution of 3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carbaldehyde (243 mg, 0.59 mmol), 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (170 mg, 0.49 mmol) and MgSO4 (710 mg, 5.90 mmol) in DCE (10 ml) was stirred for 15 min. STAB (175 mg, 0.83 mmol) was then added to the reaction mixture and stirred for 1 h at RT. The reaction was monitored by LCMS, no amine was seen after 1 h. Sat. NaHCO3 (20 ml) was added to the reaction mixture and stirred for 5 mins. Brine (10 ml) was then added to the reaction mixture. The product was extracted with DCM (2×30 ml), dried over Na2SO4, filtered and evaporated. Purification by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:99-4:96) gave the desired product (170 mg, 47%) as an oil; MS (ESI+) for C38H54F3N7O3Si m/z 742.40 [M+H]+; HPLC purity 100% (ret. time, 1.78 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm −0.25-0.11 (9H, m), 0.66-1.04 (8H, m), 1.17-1.48 (5H, m), 1.49-1.61 (3H, m), 1.77-2.04 (2H, m), 2.19-2.37 (5H, m), 2.37-2.51 (2H, m), 2.52-2.80 (2H, m), 2.81-2.91 (1H, m), 2.91-3.22 (2H, m), 3.34-3.79 (2H, m), 4.29-4.52 (1H, m), 4.78-5.12 (2H, m), 5.28-5.70 (4H, m), 6.34 (1H, d, J=3.63 Hz), 6.80-7.16 (1H, m), 7.29-7.71 (2H, m), 7.71-8.11 (1H, m), 8.11-8.46 (1H, m)

Provenance & Evidence