Reaktion #556771

Reaktionsgleichung

2-((1S,2S,5R)-3,3-difluoro-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)acetyl chloride

product

2-amino-4-(4-chlorophenyl)phthalazin-1(2H)-one

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

Lösungsmittel

CHCl3

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITreluxed for 16 hours
2. 2
   Sonstigequenched with 1M NaHCO3 (10 mL)
3. 3
   ExtraktionThe aq layer was extracted with EtOAc (2×20 mL)
4. 4
   Trocknenthe combined organic layers were dried (Na2SO4)
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated
7. 7
   SonstigeThe residue was purified by column chromatography

Vorschrift

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)+.

Quelle