Hydrochloric Acid → 4-(1h-Imidazol-2-ylcarbamoyl)-1h-benzoimidazole-2-carboxylic acid

HRID 1844974Notes

Reaction equation

HRID 1844974 reaction equation
[NH2:1][C:2]1[C:15]([NH2:16])=[CH:14][CH:13]=[CH:12][C:3]=1[C:4]([NH:6][C:7]1[NH:8][CH:9]=[CH:10][N:11]=1)=[O:5].Cl[C:18](Cl)(Cl)[C:19](N)=[O:20].Cl.[Li+].[OH-:26]>C(O)(=O)C.CO.C1COCC1>[NH:11]1[CH:10]=[CH:9][N:8]=[C:7]1[NH:6][C:4]([C:3]1[C:2]2[N:1]=[C:18]([C:19]([OH:20])=[O:26])[NH:16][C:15]=2[CH:14]=[CH:13][CH:12]=1)=[O:5]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 61144TrichloroacetamideHCID 669405262,3-Diamino-n-(1h-imidazol-2-yl)-benzamide

Product 1

HCID 669403914-(1h-Imidazol-2-ylcarbamoyl)-1h-benzoimidazole-2-carboxylic acidYield 40%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 200 mg (0.92 mmol) of 2,3-diamino-N-(1H-imidazol-2-yl)-benzamide (synthesized as described in Intermediate-B) in 2.0 mL of acetic acid was added 200 mg (1.15 mmol) of 2,2,2-trichloroacetamide and stirring continued for 30 min at r.t. Then 0.5 mL of 1% HCl in methanol was added and stirred for another 45 min at r.t. Evaporation of the solvent gave the crude ester, which was dissolved in 4:1 THF and methanol (5 mL) and then 1.0 mL of 2N LiOH was added at r.t. The reaction mixture was stirred at r.t. for 30 min, the pH was adjusted to 3.0 and then extracted with ethyl acetate twice (2×25 mL). The combined organic solvents were dried, evaporated to provide 100 mg (40%) of 4-(1H-imidazol-2-ylcarbamoyl)-1H-benzoimidazole-2-carboxylic acid, which was used, for the next step without further purification. LCMS: 272 (M+1)+.

Workup

  1. stirringstirred for another 45 min at r.t
  2. customEvaporation of the solvent
  3. customgave the crude ester, which
  4. stirringThe reaction mixture was stirred at r.t. for 30 min
  5. extractionextracted with ethyl acetate twice (2×25 mL)
  6. customThe combined organic solvents were dried
  7. customevaporated

Sources & evidence

ORD record
ord-3f1f6aef88f64666aef8c6e7f310be7a
Source dataset
uspto-grants-2015_02
Patent number
US08946259B2

Reaction notes

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