反应详情

1-Propanephosphonic acid cyclic anhydride 50 wt % solution in ethyl acetate (8.90 μL, 1.50 mmol) is added to a microwave vial containing a mixture of (4aR,7aS)-7a-(5-amino-2-fluoro-phenyl)-4a-fluoro-5,7-dihydro-4H-furo[3,4-d][1,3]thiazin-2-amine (81.2 mg, 0.285 mmol), 5-(oxetan-2-ylmethoxy)pyrazine-2-carboxylic acid (140 mg, 0.300 mmol) and anhydrous dichloromethane (10 mL). The vial is sealed and the mixture stirred at room temperature overnight. The mixture is then partitioned between water and dichloromethane and the layers separated through a Phase Separating cartridge. Organics are combined and the solvent evaporated under reduced pressure. The resulting oil is dissolved in methanol, filtered, and purified by preparative-HPLC (Phenomenex Gemini 10 μm 50*150 mm C-18) (CH3CN and water with 10 mM ammonium bicarbonate, 10% to 100% CH3CN over 10 minutes at 120 ml/min) (1 injection). Fractions bearing product are concentrated to dryness overnight in a centrifugal evaporator to give the title compound as a white solid (40 mg, 28%). ES/MS (m/e): 478.2 (M+1).

1. additioncontaining
2. customThe vial is sealed
3. customThe mixture is then partitioned between water and dichloromethane
4. customthe layers separated through a Phase
5. customSeparating cartridge
6. customthe solvent evaporated under reduced pressure
7. dissolutionThe resulting oil is dissolved in methanol
8. filtrationfiltered
9. custompurified by preparative-HPLC (Phenomenex Gemini 10 μm 50*150 mm C-18) (CH3CN and water with 10 mM ammonium bicarbonate, 10% to 100% CH3CN over 10 minutes at 120 ml/min) (1 injection)
10. concentrationare concentrated to dryness overnight in a centrifugal evaporator