反应详情

温度

120 °C

To a stirred solution of a 1:1 mixture of N1:N3 isomers of 7-fluoro-6-(4-iodo-2-methyl-phenylamino)-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid methyl ester 10jj (0.060 g, 0.108 mmol) in 1 mL DMF at room temperature under N2 is added dppf (2 mg, 0.004 mmol) followed by Pd2 dba3 (2 mg, 0.002 mmol) and Zn(CN)2 (8 mg, 0.065 mmol) (Tetrahedron Lett. 1999, 40, 8193-8195). The reaction mixture is heated to 120° C. for 45 minutes. The reaction mixture is cooled to room temperature and quenched by the addition of 5 mL of a 4:1:5 mixture of sat NH4Cl:conc NH4OH:water. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are washed with water (3×), brine, and dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography eluted with 1:1 hexanes:ethyl acetate provides 38 mg (77%) of desired product as a 1:1 mixture of N1 and N3 isomers: APCI MS (+) m/z 455 (M+1) detected.

1. additionTo a stirred solution of a 1:1 mixture of N1
2. temperatureThe reaction mixture is cooled to room temperature
3. customquenched by the addition of 5 mL of a 4:1:5 mixture of sat NH4Cl
4. extractionThe aqueous layer is extracted with ethyl acetate
5. washThe combined organic extracts are washed with water (3×), brine
6. dry with materialdried (MgSO4)
7. concentrationconcentrated under reduced pressure
8. customPurification by flash column chromatography
9. washeluted with 1:1 hexanes