Cesium carbonate → 2-(5-Dimethoxymethyl-2-nitro-phenylamino)-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide

HRID 1667707Notes

Reaction equation

HRID 1667707 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:17]([NH2:19])=[O:18])=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:16])([F:15])[F:14])[N:6]=1.[CH3:20][O:21][CH:22]([O:33][CH3:34])[C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[C:25](F)[CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:34][O:33][CH:22]([O:21][CH3:20])[C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[C:25]([NH:1][C:2]2[S:3][C:4]([C:17]([NH2:19])=[O:18])=[C:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:13]([F:16])([F:14])[F:15])[N:6]=2)[CH:24]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 540322924-Dimethoxymethyl-2-fluoro-1-nitrobenzeneHCID 59375350HCID 59375350, compound

Product 1

HCID 866428172-(5-Dimethoxymethyl-2-nitro-phenylamino)-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amideYield 68.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.20 g (0.70 mmole) of 2-amino-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide (V.17), 0.18 g (0.84 mmole) of 4-dimethoxymethyl-2-fluoro-1-nitro-benzene (IV.2a) and 1.14 g (3.5 mmole) of cesium carbonate in 12 mL of dimethylformamide was heated to 60 degrees for 3 hours, then cooled. The mixture was poured into ice water, extracted three times with ethyl acetate. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with hexanes-ethyl acetate (gradient 100:0-50:50) gave 0.23 g of 2-(5-dimethoxymethyl-2-nitro-phenylamino)-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide (VI.17a) as a yellow solid.

Workup

  1. temperaturewas heated to 60 degrees for 3 hours
  2. temperaturecooled
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by silica gel chromatography
  9. washeluting with hexanes-ethyl acetate (gradient 100:0-50:50)

Sources & evidence

ORD record
ord-586d8ed090b040078d50fdd0558aedcc
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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