반응 #59173

반응 방정식

1,2-diamino-4,5-difluorobenzene

cyanogen bromide

sodium bicarbonate

→

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

수율 98.8%

용매

water

반응 조건

후처리

1. 1
   농축was then concentrated in vacuo
2. 2
   온도heated
3. 3
   온도at reflux for 15 minutes
4. 4
   여과The hot suspension was filtered
5. 5
   세척rinsing with hot ethanol
6. 6
   농축the filtrate was concentrated in vacuo

실험 절차

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).

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