1-Hydroxybenzotriazole → 6-Methyl-4'-trifluoromethyl-biphenyl-2-carboxylic acid [4-[4-(3-cyano-benzyl)-piperazin-1-yl]-phenyl]-amide

HRID 1267126Notes

Reaction equation

HRID 1267126 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:20]=[CH:21][CH:22]=1)[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)#[N:2].[CH3:23][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([C:40](O)=[O:41])[C:29]=1[C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CCN(CC)CC>[C:1]([C:3]1[CH:4]=[C:5]([CH:20]=[CH:21][CH:22]=1)[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:40]([C:28]3[C:29]([C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:37])([F:39])[F:38])=[CH:32][CH:31]=4)=[C:24]([CH3:23])[CH:25]=[CH:26][CH:27]=3)=[O:41])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)#[N:2]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10945826[1,1'-Biphenyl]-2-carboxylic acid, 6-methyl-4'-(trifluoromethyl)-HCID 111854474-[4-(3-Cyano-benzyl)-piperazin-1-yl]-phenylamine

Product 1

HCID 98723726-Methyl-4'-trifluoromethyl-biphenyl-2-carboxylic acid [4-[4-(3-cyano-benzyl)-piperazin-1-yl]-phenyl]-amideYield 16.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of 4-[4-(3-cyano-benzyl)-piperazin-1-yl]-phenylamine (400 mg), 6-methyl-4′-trifluoromethyl-biphenyl-2-carboxylic acid (460 mg), HOBt (222 mg), and Et3N (166 mg) in CH2Cl2 (20 mL) was added at room temperature EDCl (315 mg) and the mixture was stirred at room temperature for 16 hours. The organic solution was then washed with water, with a saturated solution of NaHCO3 and dried over Na2SO4. After filtration and evaporation of the filtrate, the residue was purified by flash chromatography eluting with CH2Cl2/MeOH (98/2) and crystallized from AcOEt to give the title compound (122 mg) as white crystals.

Workup

  1. washThe organic solution was then washed with water, with a saturated solution of NaHCO3
  2. dry with materialdried over Na2SO4
  3. filtrationAfter filtration and evaporation of the filtrate
  4. customthe residue was purified by flash chromatography
  5. washeluting with CH2Cl2/MeOH (98/2)
  6. customcrystallized from AcOEt

Sources & evidence

ORD record
ord-3d60cce481a34cd4aa673a494393cd2e
Source dataset
uspto-grants-2003_04
Patent number
US06552022B1

Reaction notes

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