反应详情

A mixture of palladium acetate (2.5 mg, 0.011 mmol) and DPPP (1.6 mg, 0.0039 mmol) in ethanol (0.1 mL) was stirred for 20 minutes under nitrogen. The resulting dark suspension was added to a mixture of sodium borohydride (18 mg, 0.476 mmol) and [(3R,3aR,6R,6aS)-3-[1-allyl-6-chloro-5-(5-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-2-yl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy-tert-butyl-dimethyl-silane (50.6 mg, 0.079 mmol) in ethanol (0.9 ml). The reaction was stirred at room temperature under a nitrogen atmosphere for 2.5 hours. The reaction mixture was then purified directly on preparative silica plates (1×1000 u developed with 5% MeOH/DCM). The resulting solid was dissolved in 1M TBAF in THF (0.1 mL, 0.1 mmol) and stirred at room temperature for 1 hour. The mixture was diluted with ethyl acetate (20 mL) and washed with water (10 mL). The organic layer was washed with brine (1×5 mL), dried with MgSO4, filtered and the solvent was removed under vacuum. The resulting solid was dissolved in methanol (1.0 mL) and purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water+0.05% TFA gradient. The desired fractions were lyophilized to give the title compound as a solid. LC-MS: calculated for C1-8H19ClN6O6S 482.08 observed m/e: 483.12 (M+H)+ (Rt 0.97/2 min); 1H NMR δ (ppm) (CD3OD): 7.92 (s, 1H), 7.86 (s, 1H), 5.56 (m, 1H), 4.61 (s, 4H), 4.47 (dd, 1H), 4.29 (m, 1H), 4.18-4.10 (m, 2H), 3.90 (dd, 1H), 3.60 (dd, 1H) and 3.02 (s, 3H).

1. stirringThe reaction was stirred at room temperature under a nitrogen atmosphere for 2.5 hours
2. customThe reaction mixture was then purified directly on preparative silica plates (1×1000 u developed with 5% MeOH/DCM)
3. stirringstirred at room temperature for 1 hour
4. washwashed with water (10 mL)
5. washThe organic layer was washed with brine (1×5 mL)
6. dry with materialdried with MgSO4
7. filtrationfiltered
8. customthe solvent was removed under vacuum
9. dissolutionThe resulting solid was dissolved in methanol (1.0 mL)
10. custompurified by preparative HPLC reverse phase (C-18)
11. washeluting with a 20%-80% acetonitrile/water+0.05% TFA gradient