Sodium hydride → 2,6-dichloro-N-(6-chloro-5-fluoropyrimidin-4-yl)benzamide

Temperature

0 °C

To a solution of 6-chloro-5-fluoropyrimidin-4-amine (1.21 g, 8.2 mmol) in DMF (25 mL) at 0° C. was added NaH (60% in mineral oil, 0.46 g, 11.5 mmol). The reaction mixture was stirred at 0° C. for 20 minutes. 2,6-dichlorobenzoyl chloride (2.06 g, 9.8 mmol) was then added dropwise over 5 minutes. The reaction mixture was warmed to room temperature and stirred under nitrogen overnight. The reaction was quenched with saturated NH4Cl solution (100 mL), and extracted with EtOAc (3×100 mL). The combined organics layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography eluting with 0-25% EtOAc in hexane gradient to give the desired compound as a white solid (1.32 g, 50% yield). 1H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H), 8.10 (s, 1H), 7.39-7.35 (m, 3H). LCMS (ESI) m/z: 320.0 [M+H+].

1. temperatureThe reaction mixture was warmed to room temperature
2. stirringstirred under nitrogen overnight
3. customThe reaction was quenched with saturated NH4Cl solution (100 mL)
4. extractionextracted with EtOAc (3×100 mL)
5. dry with materialThe combined organics layer was dried over Na2SO4
6. concentrationconcentrated under reduced pressure
7. customThe crude product was purified by silica gel column chromatography
8. washeluting with 0-25% EtOAc in hexane gradient

ORD record

ord-2e1a4d6cabda4a89b22c1cee51b59ca9

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697708B2