Reacción #59173

Ecuación de reacción

1,2-diamino-4,5-difluorobenzene

cyanogen bromide

sodium bicarbonate

→

5,6-difluoro-1H-benzimidazol-2-amine

Rendimiento 98.8%

Disolventes

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónwas then concentrated in vacuo
2. 2
   Temperaturaheated
3. 3
   Temperaturaat reflux for 15 minutes
4. 4
   FiltraciónThe hot suspension was filtered
5. 5
   Lavadorinsing with hot ethanol
6. 6
   Concentraciónthe filtrate was concentrated in vacuo

Procedimiento

Step 1 The procedure used was similar to that reported in J. Med. Chem. 40:811-818, 1997. A solution of 1,2-diamino-4,5-difluorobenzene (500 mg, 3.47 mmol) in water (5 mL) was cooled to 0° C. and then treated with a solution of cyanogen bromide (0.83 mL, 4.16 mmol, 5 M in acetonitrile) and solid sodium bicarbonate (583 mg, 6.94 mmol). The solution was stirred at rt overnight and was then concentrated in vacuo. The dark residue was suspended in ethanol and heated at reflux for 15 minutes. The hot suspension was filtered, rinsing with hot ethanol, and the filtrate was concentrated in vacuo to afford 5,6-difluoro-1H-benzimidazol-2-amine (580 mg, 59%), which was used in the next step without further purification. LC-MS m/z 170.2 (MH+), ret. time 0.85 min; 1H NMR (300 MHz, DMSO-d6) δ 6.30 (br s, 2H), 7.06 (dd, 2H), 10.79 (br s, 1H).

Fuente