反应详情

MgSO4 (450 mg, 3.74 mmol) was added to a solution of 4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butanal (189 mg, 0.45 mmol) and 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (145 mg, 0.37 mmol) in DCE (10 ml) at RT and stirred for 15 mins. Na(AcO)3BH (111 mg, 0.52 mmol) was then added and continued stirring at RT for 2 hours. Sat. NaHCO3 (30 ml) was added to the reaction mixture and stirred for 5 mins. Brine (10 ml) was added to the reaction mixture, the organic layer was separated and the aqueous was further extracted with DCM (30 ml). The combined organic layers was dried over Na2SO4, filtered and evaporated. The crude mixture was dissolved in MeCN:H2O (8:2) (4 ml) and purified by preparative HPLC under acidic conditions to give a colourless oil (105 mg, 42%); MS (ESI+) for C39H55ClF3N7O3Si m/z 790.35 [M+H]+: HPLC purity 90% (ret. time, 1.90 min): 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 10.98 (1H, br. s.), 8.07 (6.98-7.10 (1H, m), 1H, d, J=1.89 Hz), 7.87-8.01 (1H, m), 7.70 (1H, s), 7.16-7.25 (1H, m), 5.50-5.69 (2H, m), 4.96 (2H, br. s.), 4.66 (1H, br. s.), 4.28-4.39 (1H, m), 3.82 (1H, br. s.), 3.55-3.69 (2H, m), 3.15-3.33 (5H, m), 3.05-3.14 (1H, m), 2.94-3.03 (1H, m), 2.49-2.83 (2H, m), 2.23-2.49 (1H, m), 1.83-2.16 (4H, m), 1.53 (3H, d, J=11.51 Hz), 1.33-1.46 (6H, m), 1.28 (3H, d, J=7.72 Hz), 0.99-1.10 (2H, m), 0.94 (4H, dd, J=3.39, 1.18 Hz), −0.26-0.15 (9H, m)

1. stirringcontinued stirring at RT for 2 hours
2. stirringstirred for 5 mins
3. customthe organic layer was separated
4. extractionthe aqueous was further extracted with DCM (30 ml)
5. dry with materialThe combined organic layers was dried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. dissolutionThe crude mixture was dissolved in MeCN:H2O (8:2) (4 ml)
9. custompurified by preparative HPLC under acidic conditions