反应详情

温度

50 °C

To a solution of N-(2-chloro-4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-N-methyl-3-(methylsulfonyl)-5-(trifluoromethyl)benzamide (0.1 g, 193 μmol, Example 212) in THF (3 mL) were added methylzinc(II)chloride (193 μL, 387 μmol), 1,3-dimethyl-2-imidazolidinone (DMI) (0.6 mL) and PEPPSI-IPr (CAS 905459-27-0) (2.7 mg, 3.87 μmol) and the reaction mixture was heated at 50° C. for 3 hours. The reaction mixture was poured on 10% aqueous citric acid solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed with brine, dried over MgSO4, filtered and evaporated. The compound was purified by silica gel chromatography on a 10 g column using an MPLC (ISCO) system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.05% triethylamine) (20:80 to 60:40). Colorless solid (0.035 g; 36%). MS (ESI): m/z=497.12 [M+H]+.

1. customthe layers were separated
2. extractionThe aqueous layer was extracted twice with EtOAc
3. washThe organic layers were washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customevaporated
7. customThe compound was purified by silica gel chromatography on a 10 g column
8. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)
9. customThe product was purified by preparative HPLC (Gemini NX column)
10. customThe product was purified by preparative HPLC (Gemini NX column)