Ammonium Chloride → 2-[5-(4-Methyl-piperazin-1-ylmethyl)-2-nitro-phenylamino]-4-(4-trifluoromethyl-phenyl)thiazole-5-carboxylic acid amide

HRID 1667791Notes

Reaction equation

HRID 1667791 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]([N+:28]([O-:30])=[O:29])=[C:7]([NH:9][C:10]2[S:11][C:12]([C:25]([NH2:27])=[O:26])=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[N:14]=2)[CH:8]=1)=O.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl-].[NH4+].C(=O)(O)[O-].[Na+]>ClCCl>[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH2:1][C:3]2[CH:4]=[CH:5][C:6]([N+:28]([O-:30])=[O:29])=[C:7]([NH:9][C:10]3[S:11][C:12]([C:25]([NH2:27])=[O:26])=[C:13]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([F:23])([F:22])[F:24])=[CH:17][CH:16]=4)[N:14]=3)[CH:8]=2)[CH2:34][CH2:33]1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 866428502-(5-Formyl-2-nitro-phenylamino)-4-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide

Product 1

HCID 866428512-[5-(4-Methyl-piperazin-1-ylmethyl)-2-nitro-phenylamino]-4-(4-trifluoromethyl-phenyl)thiazole-5-carboxylic acid amideYield 59.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 0.1041 g (0.239 mmole) of 2-(5-formyl-2-nitro-phenylamino)-4-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide (VI.47b), 5 mL of dichloromethane, 0.0781 g (0.772 mmole) of 1-methyl piperazine and 0.2665 (1.195 mmole) of sodium triacetoxyborohydride was stirred for 15 hours. The mixture was treated with 1 mL of saturated ammonium chloride, followed by 10 mL of saturated sodium bicarbonate and 5 mL of dichloromethane. The mixture was stirred for 45 minutes. The aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with methanol-dichloromethane (gradient 1:99-20:80) to give 0.074 g of 2-[5-(4-methyl-piperazin-1-ylmethyl)-2-nitro-phenylamino]-4-(4-trifluoromethyl-phenyl)thiazole-5-carboxylic acid amide (VI.47c) as a light orange solid.

Workup

  1. stirringThe mixture was stirred for 45 minutes
  2. extractionThe aqueous layer was extracted twice with dichloromethane
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with methanol-dichloromethane (gradient 1:99-20:80)

Sources & evidence

ORD record
ord-993cc1a28a43476e880a4636852bc2b2
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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