Reacción #60321

Ecuación de reacción

7-fluoro-6-(4-iodo-2-methyl-phenylamino)-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid methyl ester

DMF

→

desired product

Rendimiento 77.0%

6-(4-Cyano-2-methyl-phenylamino)-7-fluoro-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid methyl ester

Rendimiento 77.0%

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONTo a stirred solution of a 1:1 mixture of N1
2. 2
   TemperaturaThe reaction mixture is cooled to room temperature
3. 3
   Otroquenched by the addition of 5 mL of a 4:1:5 mixture of sat NH4Cl
4. 4
   ExtracciónThe aqueous layer is extracted with ethyl acetate
5. 5
   LavadoThe combined organic extracts are washed with water (3×), brine
6. 6
   Secadodried (MgSO4)
7. 7
   Concentraciónconcentrated under reduced pressure
8. 8
   OtroPurification by flash column chromatography
9. 9
   Lavadoeluted with 1:1 hexanes

Procedimiento

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.

Fuente