Reacción #60282

Ecuación de reacción

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide

cyanogen bromide

NaHCO3

→

pure desired product

Rendimiento 55.0%

[6-(5-Amino-[1,3,4]oxadiazol-2-yl)-4-fluoro-1H-benzoimidazol-5-yl]-(4-bromo-2-methyl-phenyl)-amine

Rendimiento 55.0%

Disolventes

methylene chloride

water

brine

1,4-dioxane

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracted with THF
2. 2
   SecadoThe combined organic extracts are dried (Na2SO4)
3. 3
   Concentraciónconcentrated under reduced pressure
4. 4
   OtroPurification by FCC
5. 5
   Lavadoeluted with 98:2 ethyl acetate

Procedimiento

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide 20a (0.041 g, 0.109 mmol) is suspended in 1,4-dioxane (1.5 mL) and 36 μL of a 3 M solution of cyanogen bromide in methylene chloride is added. NaHCO3 (9 mg, 0.109 mmol) in water (1.5 mL) is then added. After 16 hours, the reaction mixture is diluted with water and brine and extracted with THF. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Purification by FCC eluted with 98:2 ethyl acetate:MeOH provides 24 mg (55%) of pure desired product as a yellow solid: LC/MS ESI (+) m/z 403, 405 (M+Br pattern) detected; 1H-NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 8.42 (s, 1H), 7.94 (s, 1H), 7.74 (s, 1H), 7.36 (s, 2H), 7.33 (d, 1H), 7.15 (d, 1H), 6.40 (bs, 1H), 2.34 (s, 3H).

Fuente