Formic Acid → 4-(3-Chloro-phenyl)-2-[6-(2-hydroxy-ethoxy)-5-methoxy-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide

HRID 1667776Notes

Reaction equation

HRID 1667776 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([NH:16][C:17]3[CH:22]=[C:21]([O:23][CH2:24][CH2:25][O:26]C4CCCCO4)[C:20]([O:33][CH3:34])=[CH:19][C:18]=3[N+:35]([O-])=O)[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1.[H][H].[CH:40](O)=O>[Pd]>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([N:16]3[C:17]4[CH:22]=[C:21]([O:23][CH2:24][CH2:25][OH:26])[C:20]([O:33][CH3:34])=[CH:19][C:18]=4[N:35]=[CH:40]3)[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 284Formic AcidHCID 866428404-(3-Chloro-phenyl)-2-{4-methoxy-2-nitro-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenylamino}-thiazole-5-carboxylic acid amideHCID 178418361HCID 178418361, compound

Product 1

HCID 674458254-(3-Chloro-phenyl)-2-[6-(2-hydroxy-ethoxy)-5-methoxy-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

A mixture of 0.470 g (0.86 mmole) of 4-(3-chloro-phenyl)-2-{4-methoxy-2-nitro-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenylamino}-thiazole-5-carboxylic acid amide (VI.44), 0.250 g of 10% palladium on carbon catalyst and 3 mL of 96% formic acid was stirred under 1 atmosphere of hydrogen for 16 hours. The mixture was filtered through diatomaceous earth and the diatomaceous earth pad was washed with formic acid. The filtrate was heated at reflux for 2 hours, cooled and concentrated under reduced pressure. The residue was dissolved in 5 mL of dimethylsulfoxide and 0.20 g of potassium hydroxide in 1 mL of water was added dropwise. The mixture was stirred at room temperature for 30 minutes and then diluted with 50 mL of water. The resulting precipitate was collected by filtration and washed with water to give 0.190 g of 4-(3-chloro-phenyl)-2-[6-(2-hydroxy-ethoxy)-5-methoxy-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide (I.44a) as a purple solid.

Workup

  1. filtrationThe mixture was filtered through diatomaceous earth
  2. washthe diatomaceous earth pad was washed with formic acid
  3. temperatureThe filtrate was heated
  4. temperatureat reflux for 2 hours
  5. temperaturecooled
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in 5 mL of dimethylsulfoxide
  8. addition0.20 g of potassium hydroxide in 1 mL of water was added dropwise
  9. additiondiluted with 50 mL of water
  10. filtrationThe resulting precipitate was collected by filtration
  11. washwashed with water

Sources & evidence

ORD record
ord-b0a558f730c54e6ea983b7d057b74c4c
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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