3,5-Diamino-2-methylbenzoic acid → 2-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 470348Notes

Reaction equation

HRID 470348 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.[CH3:18][O:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([NH2:28])[CH:22]=1>CC(N(C)C)=O>[CH3:18][O:19][C:20]([C:21]1[CH:26]=[CH:25][C:24]2[N:27]=[C:4]([C:3]3[CH:6]=[C:7]([C:10]4[C:11]([O:16][CH3:17])=[N:12][CH:13]=[CH:14][CH:15]=4)[CH:8]=[CH:9][C:2]=3[OH:1])[NH:28][C:23]=2[CH:22]=1)=[O:29]

Participants

4

Reactant 2

HCID 1355243,5-Diamino-2-methylbenzoic acidHCID 59784178HCID 59784178, compound

Product 1

HCID 1361065952-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid methyl esterYield 42%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cold flask with a rubber stopper were added 2-hydroxy-5-(2-methoxy-pyridin-3-yl)-benzaldehyde (2.29 g, 10 mol) and 3,4-diamino-benzoic acid methyl ester (1.83 g, 11 mmol) and the solid mixture was stirred at 0° C. for 15 min. Then DMA (10 mL) was added into the mixture via a syringe and the resulting solution was stirred at 0° C. for 1.5 h, and at the room temperature for 1.5 h. The rubber stopper was removed and the reaction mixture was stirred at 110° C. for 14 h open to the air. The DMA was removed under reduced pressure and the residue was mixed with 50 mL MeOH, and sonicated for 15 min. The mixture was filtered to get the solid precipitate, which was re-crystallized in 300 mL MeOH to afford the title compound (1.6 g, 42%). 1H NMR (DMSO-d6) δ 3.90 (s, 3H), 3.93 (s, 3H), 7.12-7.17 (2H), 7.65 (d, J=9 Hz, 1H), 7.76 (d, J=9 Hz, 1H), 7.83 (d, J=9 Hz, 1H), 7.91 (d, J=9 Hz, 1H), 8.20 (d, J=6 Hz, 1H), 8.26 (s, 1H), 8.29 (s, 1H). ESI-MS m/z 376.3 (MH+).

Workup

  1. stirringthe resulting solution was stirred at 0° C. for 1.5 h
  2. waitat the room temperature for 1.5 h
  3. customThe rubber stopper was removed
  4. stirringthe reaction mixture was stirred at 110° C. for 14 h open to the air
  5. customThe DMA was removed under reduced pressure
  6. additionthe residue was mixed with 50 mL MeOH
  7. customsonicated for 15 min
  8. filtrationThe mixture was filtered
  9. customto get the solid precipitate, which
  10. customwas re-crystallized in 300 mL MeOH

Sources & evidence

ORD record
ord-b3fbf7a1864943bc92c9594c957753f4
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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