Formic Acid → 2-[6-(4-Methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide

HRID 1667710Notes

Reaction equation

HRID 1667710 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([N+:34]([O-])=O)=[C:13]([NH:15][C:16]3[S:17][C:18]([C:31]([NH2:33])=[O:32])=[C:19]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[C:27]([F:30])([F:29])[F:28])[N:20]=3)[CH:14]=2)[CH2:4][CH2:3]1.[CH:37](O)=O>[Pd]>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]3[N:34]=[CH:37][N:15]([C:16]4[S:17][C:18]([C:31]([NH2:33])=[O:32])=[C:19]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=5[C:27]([F:30])([F:29])[F:28])[N:20]=4)[C:13]=3[CH:14]=2)[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 284Formic AcidHCID 866428192-[5-(4-Methyl-piperazin-1-ylmethyl)-2-nitro-phenylamino]-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide

Product 1

HCID 468308712-[6-(4-Methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

A mixture of 0.060 g (0.12 mmole) of 2-[5-(4-methyl-piperazin-1-ylmethyl)-2-nitro-phenylamino]-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide (VI.17c) in 7 mL of formic acid and 0.007 g of 10% palladium on carbon catalyst was stirred under an atmosphere of hydrogen for 18 hours. The mixture was filtered through a pad of Diatomaceous earth, washing the filter pad with dichloromethane. The filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane and saturated sodium bicarbonate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification of the residue by silica gel chromatography, eluting with dichloromethane-methanol (gradient 100:0-75:25) gave 0.034 g of 2-[6-(4-methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-(2-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide (I.17) as a white solid. MH+/Z=501

Workup

  1. filtrationThe mixture was filtered through a pad of Diatomaceous earth
  2. washwashing the filter pad with dichloromethane
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. additionThe residue was diluted with dichloromethane and saturated sodium bicarbonate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the residue by silica gel chromatography
  9. washeluting with dichloromethane-methanol (gradient 100:0-75:25)

Sources & evidence

ORD record
ord-540247e0c7bb45c7be600a7b80d19a79
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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