Pyridine → N-[4-(4-chlorophenyl)-1-oxophthalazin-2(1H)-yl]-2-[(1S,2S,5R)-3,3-difluoro-6,6-dimethylbicyclo[3.1.1]hept-2-yl]acetamide

Participants

Reaction Steps

To a mixture of the above crude 2-((1S,2S,5R)-3,3-difluoro-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)acetyl chloride (50 mg, 0.211 mmol) and the product from Example 86A (57.4 mg, 0.211 mmol) in 10 mL of CHCl3 was added pyridine (0.051 mL, 0.634 mmol). The reaction is stirred at rt for 12 hours and then reluxed for 16 hours, and quenched with 1M NaHCO3 (10 mL). The aq layer was extracted with EtOAc (2×20 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-40% of EtOAc in hexanes). 1H NMR (300 MHz, DMSO-d6) δ ppm 11.51 (s, 1H), 8.39-8.43 (m, 1H), 7.94-8.00 (m, 2H), 7.70-7.76 (m, 1H), 7.58-7.70 (m, 4H), 2.92-3.09 (m, 1H), 2.81 (dd, J=15.3, 6.4 Hz, 1H), 2.36-2.45 (m, 3H), 2.11-2.16 (m, 1H), 1.93-2.04 (m, 1H), 1.27 (s, 3H), 1.08-1.20 (m, 2H), 1.01 (s, 3H); MS (ESI+) M/Z 472 (M+H)+.

Provenance & Evidence