反应详情

Oxalyl chloride (507.70 μL; 6 mmol) was added to suspension of 5,6-dichloronicotinic acid (FLUKA; 36000-10G; 384 mg; 2 mmol) and DMF (15.40 μL; 0.20 mmol) in DCM (30 mL) and the resulting mixture was stirred at RT for 1 hour. The solution was then evaporated to dryness. The residue was dissolved in THF (5 mL) and added dropwise to a mixture of Intermediate 1 (424.36 mg; 2 mmol), DIEA (1.03 mL; 6 mmol) in THF (5 mL). The reaction mixture was heated in the microwave at 150° C. for 30 min. When cool to RT the solid was filtered, rinsed with ACN, dissolved in DCM and washed with water. The organic layer was then dried over magnesium sulfate, filtered and concentrated to afford the title compound as a slightly yellow solid. 1H NMR (DMSO-d6, 300 MHz) δ 9.18-9.17 (m, 1H), 8.90-8.89 (m, 1H), 8.17-8 (m, 3H), 3.91 (s, 3H). 19F NMR (DMSO-d6, 300 MHz) δ-108.7 ppm. HPLC (Method A) Rt 5.19 min (Purity: 98.0%).

1. customThe solution was then evaporated to dryness
2. dissolutionThe residue was dissolved in THF (5 mL)
3. temperatureThe reaction mixture was heated in the microwave at 150° C. for 30 min
4. temperatureWhen cool to RT the solid
5. filtrationwas filtered
6. washrinsed with ACN
7. dissolutiondissolved in DCM
8. washwashed with water
9. dry with materialThe organic layer was then dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated