Dimethylformamide → 3-{4-[6-(4-tert-butylphenylcarbamoyl)-1H-benzimidazol-2-yl]-3,5-dimethylphenyl}-propionic acid methyl ester

HRID 1515032Notes

Reaction equation

HRID 1515032 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[NH2:21])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:10][CH:9]=1)=[O:6].[CH3:22][O:23][C:24](=[O:37])[CH2:25][CH2:26][C:27]1[CH:32]=[C:31]([CH3:33])[C:30]([CH:34]=O)=[C:29]([CH3:36])[CH:28]=1.OOS([O-])=O.[K+].CN(C=O)C>C(OCC)(=O)C>[CH3:22][O:23][C:24](=[O:37])[CH2:25][CH2:26][C:27]1[CH:32]=[C:31]([CH3:33])[C:30]([C:34]2[NH:1][C:2]3[CH:3]=[C:4]([C:5](=[O:6])[NH:7][C:8]4[CH:13]=[CH:12][C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:10][CH:9]=4)[CH:18]=[CH:19][C:20]=3[N:21]=2)=[C:29]([CH3:36])[CH:28]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 23707502Potassium hydroxy sulfiteHCID 54209618Methyl 3-(3,5-dimethyl-4-formylphenyl)propionateHCID 669661113,4-diamino-N-(4-tert-butylphenyl)-benzamide

Product 1

HCID 669656413-{4-[6-(4-tert-butylphenylcarbamoyl)-1H-benzimidazol-2-yl]-3,5-dimethylphenyl}-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3,4-diamino-N-(4-tert-butylphenyl)-benzamide (200 mg, 710 μmol), 3-(4-formyl-3,5-dimethylphenyl)-propionic acid methyl ester (190 mg, 860 μmols) (from Example 6-17) and oxone (286 mg, 470 μmols) in a solution of 5 mL DMF/0.5 mL water was stirred at ambient temperature for 1 h. The mixture was poured into ethyl acetate and extracted once with water and five times with brine. The organic phase was dried, filtered, and the solvent was removed under reduced pressure. The residue was purified by chromatography using a gradient of 50-90% heptane/ethyl acetate to afford 3-{4-[6-(4-tert-butylphenylcarbamoyl)-1H-benzimidazol-2-yl]-3,5-dimethylphenyl}-propionic acid methyl ester. 1H-NMR (CDCl3, 400 MHz): δ 8.51 (s, broad, 1H), 8.07 (s, broad, 1H), 7.58 (d, J=8.5 Hz, 1H), 7.53 (d, J=8.1 Hz, 2H), 7.31 (d, J=8.6 Hz, 2H), 6.82 (s, 2H), 3.63 (s, 3H), 2.89 (t, J=7.4 Hz, 2H), 2.63 (t, J=7.4 Hz, 2H), 1.92 (s, 6H), 1.30 (s, 9H). MS (ESI) m/z 484.3 (M+H).

Workup

  1. extractionextracted once with water and five times with brine
  2. customThe organic phase was dried
  3. filtrationfiltered
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-abfbab5613a840b7b0d924a9511e3902
Source dataset
uspto-grants-2012_07
Patent number
US08222248B2

Reaction notes

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