Acetone → HCID 57707784, compound

Participants

Reaction Conditions

Reaction Steps

2-((5-amino-3-(2-chlorophenyl)quinoxalin-2-yl)methyl)isoindoline-1,3-dione (Prepared in Example 97, 0.8364 g, 2.016 mmol) was dissolved in acetone (28.80 mL, 2.016 mmol) and cooled to 0° C. While being stirred, the solution was treated first with 2 M hydrochloric acid (5.645 mL, 11.29 mmol) and then dropwise with 1 M aq. sodium nitrite (6.049 mL, 6.049 mmol) while maintaining the temperature of the mixture at 0° C. After the additions were complete, the mixture was stirred for 15 min and then treated with 5 M aq. potassium iodide (4.839 mL, 24.19 mmol) maintaining the temperature below 5° C. The mixture was then allowed to warm to 15° C. over 3 h. The acetone was removed under reduced pressure, and the residue was partitioned between water (100 mL) and ethyl acetate (100 mL). The organic solution was washed with 10% aqueous sodium bisulfite (100 mL×3) and saturated aqueous sodium bicarbonate (100 mL×1), brine (100 mL×1), dried over MgSO4, filtered, and concentrated under reduced pressure to give a red solid. The red solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and then 50% isocratic of EtOAc in hexane for 25 min as eluent to give 2-((3-(2-chlorophenyl)-5-iodoquinoxalin-2-yl)methyl)-isoindoline-1,3-dione as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (1H, dd, J=7.4, 1.2 Hz), 7.97 (1H, dd, J=8.2, 1.2 Hz), 7.83-7.91 (4H, m), 7.51-7.75 (5H, m), 4.96 (2H, d, J=21.9 Hz); LC-MS (ESI) m/z 526.0 [M+H]+.

Provenance & Evidence