Hydrochloric Acid → 7-Fluoro-2-methyl-6-phenylamino-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 2104075Notes

Reaction equation

HRID 2104075 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([NH2:10])[C:7]([NH2:11])=[C:6]([F:12])[C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl.[CH3:22][C:23](=O)CC(=O)C.C([O-])(O)=O.[Na+]>C(O)C>[CH3:1][O:2][C:3]([C:4]1[C:5]([NH:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[C:6]([F:12])[C:7]2[N:11]=[C:22]([CH3:23])[NH:10][C:8]=2[CH:9]=1)=[O:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31261AcetylacetoneHCID 516892Sodium BicarbonateHCID 56604175Methyl 4,5-diamino-3-fluoro-2-(phenylamino)benzoate

Product 1

HCID 668978577-Fluoro-2-methyl-6-phenylamino-3H-benzoimidazole-5-carboxylic acid methyl esterYield 91.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

4,5-Diamino-3-fluoro-2-phenylamino-benzoic acid methyl ester 6c (0.20 g, 0.73 mmol) is suspended in ethanol (3 mL) and 5 M aqueous HCl (1 mL., 5.00 mmol) is added. The reaction mixture is brought to reflux under N2 and then 2,4-pentanedione (0.150 mL, 1.45 mmol) is added. The reaction mixture is stirred at reflux for 60 minutes. The reaction mixture is cooled to room temperature and treated with saturated aqueous NaHCO3 until the pH of the reaction mixture is pH 7 and is then concentrated under reduced pressure to dryness. The residue is diluted with ethyl acetate and water, poured into a separatory funnel and the layers separated. The ethyl acetate layer is washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The red solid residue is triturated with diethyl ether to yield a light brown solid and a red filtrate. The solid is collected and washed with diethyl ether to yield 0.20 g (91%) of the pure desired product as a light brown solid. MS ESI (+) m/z 300 (M+1) detected.

Workup

  1. temperatureto reflux under N2
  2. temperatureat reflux for 60 minutes
  3. concentrationis then concentrated under reduced pressure to dryness
  4. additionThe residue is diluted with ethyl acetate and water
  5. additionpoured into a separatory funnel
  6. customthe layers separated
  7. washThe ethyl acetate layer is washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe red solid residue is triturated with diethyl ether
  11. customto yield a light brown solid
  12. customThe solid is collected
  13. washwashed with diethyl ether

Sources & evidence

ORD record
ord-467b071faea54f03a1cfb21b22c3843d
Source dataset
uspto-grants-2009_08
Patent number
US07576114B2

Reaction notes

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