Cesium carbonate → 2-[(2,5-dichloropyridin-4-yl)amino]-3-fluoro-N-methylbenzamide

Temperature

80 °C

Palladium(II) acetate (35.9 mg, 0.16 mmol) was added to 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (139 mg, 0.24 mmol), cesium carbonate (2604 mg, 7.99 mmol), 2,5-dichloro-4-iodopyridine (1094 mg, 4.00 mmol) and 2-amino-3-fluoro-N-methylbenzamide (672 mg, 4.00 mmol) in dioxane (20 mL) under an atmosphere of nitrogen. The resulting suspension was heated at 80° C. for 24 hours and then allowed to cool to room temperature. The mixture was evaporated and the residue dissolved in EtOAc (150 mL) and then washed sequentially with a saturated solution of NaHCO3 (100 mL), water (100 mL), and then with a saturated solution of NaCl (100 mL). The organic layer was dried over MgSO4 and then evaporated. The residue was purified by chromatography on silica, eluting with a gradient of 0-100% EtOAc in isohexane. Fractions containing product were evaporated to afford 2-[(2,5-dichloropyridin-4-yl)amino]-3-fluoro-N-methylbenzamide (624 mg, 50% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 1H NMR (300.132 MHz, DMSO) δ 2.74 (3H, d), 6.39 (1H, d), 7.42 (1H, td), 7.49-7.59 (2H, m), 8.25 (1H, s), 8.64 (1H, m), 9.31 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+ =314.20 and 316.20 and 318.17.

1. temperatureto cool to room temperature
2. customThe mixture was evaporated
3. dissolutionthe residue dissolved in EtOAc (150 mL)
4. washwashed sequentially with a saturated solution of NaHCO3 (100 mL), water (100 mL)
5. dry with materialThe organic layer was dried over MgSO4
6. customevaporated
7. customThe residue was purified by chromatography on silica
8. washeluting with a gradient of 0-100% EtOAc in isohexane
9. additionFractions containing product
10. customwere evaporated

ORD record

ord-1c7e5e3c6b1e48a78d7ec19c009dcd29

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569298B2