Cyanogen Bromide → 5,6-difluoro-1H-1,3-benzodiazol-2-amine

HRID 30895

Reaction equation

HRID 30895 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[NH2:10].[N:11]#[C:12]Br.C(=O)(O)[O-].[Na+]>O>[F:8][C:6]1[C:5]([F:9])=[CH:4][C:3]2[NH:10][C:12]([NH2:11])=[N:1][C:2]=2[CH:7]=1

Participants

5

Reactant 3

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 27367551,2-Diamino-4,5-difluorobenzene

Product 1

HCID 106787085,6-difluoro-1H-1,3-benzodiazol-2-amineYield 98.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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).

Workup

  1. concentrationwas then concentrated in vacuo
  2. temperatureheated
  3. temperatureat reflux for 15 minutes
  4. filtrationThe hot suspension was filtered
  5. washrinsing with hot ethanol
  6. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-3205d5ce1204465dacc8103cd5057f8c
Source dataset
uspto-grants-2008_09
Patent number
US07423156B2

Linked notes

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