反应详情

A solution of 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (1 g, 3.35 mmol) in N,N-dimethylacetamide (30 mL) was treated with 4-hydroxypiperidine (396 mg, 3.92 mmol) and triethylamine (1 mL, 7.17 mmol). O-Benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (1.77 g, 4.67 mmol) was added and the resulting solution was stirred at ambient temperature for 17 hours. The reaction mixture was then poured into water (300 mL) and extracted with dichloromethane (2×200 mL). Combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and evaporated to afford the crude product, which was purified by flash silica chromatography, elution gradient 0 to 20% MeOH in dichloromethane. Pure fractions were evaporated to dryness to afford the desired compound as a pale yellow gum (1.24 g, 97% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.42-1.54 (1H, m), 1.55-1.67 (2H, m), 1.76-1.84 (1H, m), 1.92-2.01 (1H, m), 3.05-3.15 (1H, m), 3.38-3.55 (2H, m), 3.94-3.99 (1H, m), 4.14-4.22 (1H, m), 4.27 (2H, s), 7.02 (1H, t), 7.26-7.32 (2H, m), 7.70-7.79 (3H, m), 8.44-8.48 (1H, m), 10.07 (1H, s); m/z (LC-MS, ESI+), RT=1.44 (M+H 382.1).

1. extractionextracted with dichloromethane (2×200 mL)
2. washCombined organic extracts were washed with brine
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. customevaporated
6. customto afford the crude product, which
7. customwas purified by flash silica chromatography, elution gradient 0 to 20% MeOH in dichloromethane
8. customPure fractions were evaporated to dryness