反应详情

To a solution of tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate hydrochloride (850 mg, 3.23 mmol) and 5-pyrimidin-2-ylindan-1-one (SM-1b, 680 mg, 3.23 mmol) in dichloromethane (10 mL) under nitrogen was added triethylamine (2.5 mL, 17.9 mmol) followed by titanium isopropoxide (2.9 mL, 9.70 mmol). The reaction was stirred at room temperature for 90 minutes and sodium triacetoxyborohydride (2.1 g, 9.9 mmol) was added. After stirring for 4 days, the reaction was quenched with saturated ammonium chloride. The mixture was diluted with 50 mL of dichloromethane and 50 mL of water and filtered through a Celite® pad. The aqueous layer was extracted with dichloromethane (2×30 mL). The combined organics layers were washed with brine and dried over MgSO4. The solvent was removed to give a dark green/brown paste which was chromatographed on a Combiflash ISCO purification system (Teledyne Corp., Lincoln Nebr.) using a dichloromethane/MeOH gradient to afford the title compound as light brown oil (785 mg, 57.7%). MS (ES+) 421.2 (M+H)+. 1H NMR (CDCl3) δ 1.39 (s, 9H), 1.59-1.69 (m, 4H), 1.75-1.94 (m, 1H), 2.12 (dq, 1H), 2.76-2.92 (m, 1H), 2.95-3.18 (m, 5H), 3.19-3.36 (m, 4H), 3.92 (dd, 1H), 7.09 (t, 1H), 7.33 (d, 1H), 8.18-8.26 (m, 2H), 8.71 (d, 2H).

1. stirringAfter stirring for 4 days
2. customthe reaction was quenched with saturated ammonium chloride
3. additionThe mixture was diluted with 50 mL of dichloromethane and 50 mL of water
4. filtrationfiltered through a Celite® pad
5. extractionThe aqueous layer was extracted with dichloromethane (2×30 mL)
6. washThe combined organics layers were washed with brine
7. dry with materialdried over MgSO4
8. customThe solvent was removed
9. customto give a dark green/brown paste which
10. customwas chromatographed on a Combiflash ISCO purification system (Teledyne Corp., Lincoln Nebr.)