Citric Acid → HCID 71267549, compound

HRID 1505781Notes

Reaction equation

HRID 1505781 reaction equation
[OH:1][CH2:2][C:3]1[NH:7][C:6]2[CH:8]=[C:9]([NH:15][C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])=[O:17])[CH:10]=[C:11]([C:12](O)=[O:13])[C:5]=2[N:4]=1.C([N:31](CC)[CH:32]([CH3:34])[CH3:33])(C)C.[C:37](Cl)(=O)[CH3:38].C(O)(=O)CC([CH2:48][C:49]([OH:51])=O)(C(O)=O)O.[CH2:54]([Cl:56])Cl.[CH2:57]1COCC1>>[C:49]([O:1][CH2:2][C:3]1[NH:7][C:6]2[CH:8]=[C:9]([NH:15][C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:26])([F:25])[F:27])=[O:17])[CH:10]=[C:11]([C:12](=[O:13])[NH:31][C:32]3[CH:33]=[CH:38][CH:37]=[C:54]([Cl:56])[C:34]=3[CH3:57])[C:5]=2[N:4]=1)(=[O:51])[CH3:48]

Participants

6

Reactant 5

HCID 311Citric AcidHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 21919333Tetrahydrofurane dichloromethaneHCID 90229257HCID 90229257, compound

Product 1

HCID 71267549HCID 71267549, compound

Procedure

A mixture of 2-(hydroxymethyl)-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxylic acid (50 mg) and N,N-diisopropylethylamine (49 μL) in methylene chloride-THF (1:1) (2 mL) was stirred under ice-cooling, acetyl chloride (19 μL) was added, and it was stirred at room temperature overnight. The reaction mixture was poured into a cold 10% aqueous citric acid solution, and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in DMF (3 mL), HBTU (65 mg) and triethylamine (24 μL) were added, and it was stirred at room temperature. To the mixture was added 3-chloro-2-methylaniline (16 μL) and it was stirred overnight. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

Workup

  1. temperaturecooling
  2. stirringit was stirred at room temperature overnight
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in DMF (3 mL)
  9. additionHBTU (65 mg) and triethylamine (24 μL) were added
  10. stirringit was stirred at room temperature
  11. additionTo the mixture was added 3-chloro-2-methylaniline (16 μL) and it
  12. stirringwas stirred overnight
  13. additionThe reaction mixture was poured into ice water
  14. extractionextracted with ethyl acetate
  15. washThe organic layer was washed sequentially with water and brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ea7a4f8b9a3943109dd6176537cc9524
Source dataset
uspto-grants-2015_12
Patent number
US09216968B2

Reaction notes

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