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

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 (9 H, m), 0.66-1.04 (8 H, m), 1.17-1.48 (5 H, m), 1.49-1.61 (3 H, m), 1.77-2.04 (2 H, m), 2.19-2.37 (5 H, m), 2.37-2.51 (2 H, m), 2.52-2.80 (2 H, m), 2.81-2.91 (1 H, m), 2.91-3.22 (2 H, m), 3.34-3.79 (2 H, m), 4.29-4.52 (1 H, m), 4.78-5.12 (2 H, m), 5.28-5.70 (4 H, m), 6.34 (1 H, d, J=3.63 Hz), 6.80-7.16 (1 H, m), 7.29-7.71 (2 H, m), 7.71-8.11 (1 H, m), 8.11-8.46 (1 H, m)

1. additionSTAB (175 mg, 0.83 mmol) was then added to the reaction mixture
2. stirringstirred for 5 mins
3. extractionThe product was extracted with DCM (2×30 ml)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customevaporated
7. customPurification by silica gel column chromatography
8. washeluting with 7N NH3 in MeOH:DCM (1:99-4:96)

ORD record

ord-192559f9ffec49d9bf98ecf4c6d3ba5f

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580762B2