Ethyl Acetate → 2-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid

HRID 470352Notes

Reaction equation

HRID 470352 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]([O:16][CH3:17])=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:6][C:3]=1[CH:4]=O.[NH2:18][C:19]1[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=1[NH2:28])[C:22]([OH:24])=[O:23].CCOC(C)=O>CC(N(C)C)=O>[OH:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]([O:16][CH3:17])=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:6][C:3]=1[C:4]1[NH:18][C:19]2[CH:20]=[C:21]([C:22]([OH:24])=[O:23])[CH:25]=[CH:26][C:27]=2[N:28]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 692633,4-Diaminobenzoic acidHCID 59784178HCID 59784178, compound

Product 1

HCID 1361063252-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To mixture of 2-hydroxy-5-(2-methoxy-pyridin-3-yl)-benzaldehyde (22.35 g, 0.0975 mol) and 3,4-diamino-benzoic acid (17.2 g, 0.113 mol) was added DMA (120 mL) via a syringe and the resulting solution was stirred at 0° C. for 2 h, and at the room temperature for 3 h. The robber stopper was removed and the reaction mixture was heated at 110° C. for 14 h open to the air. The DMA was removed under reduced pressure and the residue was mixed with 200 mL EtOAc, and sonicated for 15 min. The mixture was filtered to get the solid precipitate, which was mixture with 150 mL EtOAc, and sonicated for 5 min. The resulting mixture was filtered to get the solid crude that was dried at 40° C. for 6 h under reduced pressure to afford a mixture of the title compound and DMA (ratio 1:1) (16.15 g, 38%). 1H NMR (DMSO-d6) δ 3.92 (s, 3H), 7.14 (m, 1H), 7.15 (s, 1H), 7.64 (d, J=6 Hz, 1H), 7.74 (d, J=6 Hz, 1H), 7.84 (d, J=6 Hz, 1H), 7.91 (d, J=6 Hz, 1H), 8.19 (d, J=6 Hz, 1H), 8.21 (d, J=6 Hz, 1H), 8.29 (s, 1H). DMA also shows as 61.96 (s, 3H), 2.79 (s, 3H) and 2.94 (s, 3H). ESI-MS m/z 362.5 (MH+).

Workup

  1. waitat the room temperature for 3 h
  2. customThe robber stopper was removed
  3. temperaturethe reaction mixture was heated at 110° C. for 14 h open to the air
  4. customThe DMA was removed under reduced pressure
  5. additionthe residue was mixed with 200 mL EtOAc
  6. customsonicated for 15 min
  7. filtrationThe mixture was filtered
  8. customto get the solid precipitate, which
  9. customsonicated for 5 min
  10. filtrationThe resulting mixture was filtered
  11. customto get the solid crude that
  12. customwas dried at 40° C. for 6 h under reduced pressure
  13. customto afford

Sources & evidence

ORD record
ord-b3f6400ef0464d68b2cde403a6b94e79
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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