反应详情

MgSO4 (1.08 g, 9.0 mmol) was added to a solution of 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 (330 mg, 0.96 mmol) and 4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butanal (526 mg, 0.90 mmol) in DCE (10 ml) and stirred at RT for 15 mins. NaBH(OAc)3 (267 mg, 1.26 mmol) was then added to the reaction mixture and stirred for 1 hr. LC MS indicated complete consumption of the amine. Sat. NaHCO3 (20 ml) was 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 (1:199-3:97) afforded the desired product as an off white/pink foamy solid (278 mg, 41%); MS (ESI+) for C36HClF3N7O3Si m/z 748.05 [M+H]+; HPLC purity 84% (ret. Time, 1.73 min). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.30 (1H, s), 7.39-8.21 (2H, m), 6.84-7.17 (1H, m), 6.63 (1H, br. s.), 5.43-5.55 (2H, m), 5.33-5.41 (1H, m), 4.82-5.14 (2H, m), 4.54 (1H, t, J=6.23 Hz), 3.53 (4H, dd, J=16.16, 8.12 Hz), 2.89-3.13 (3H, m), 2.82 (1H, d, J=7.41 Hz), 2.66-2.80 (2H, m), 2.45 (1H, s), 2.24-2.39 (1H, m), 2.18 (1H, s), 1.83-2.06 (2H, m), 1.63-1.73 (2H, m), 1.55-1.61 (3H, m), 1.30 (3H, s), 0.81-1.03 (4H, m), 0.56-0.78 (2H, m), −0.22-0.12 (9H, m).

1. stirringstirred for 1 hr
2. customconsumption of the amine
3. additionSat. NaHCO3 (20 ml) was added to the reaction mixture
4. extractionThe product was extracted with DCM (2×30 ml)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. customPurification by silica gel column chromatography
9. washeluting with 7N NH3 in MeOH:DCM (1:199-3:97)