benzyl 4-((6-(2-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamido)pyridin-3-yl)methyl)piperazine-1-carboxylate → N-(5-(piperazin-1-ylmethyl)pyridin-2-yl)-2-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamide

HRID 85158Notes

Reaction equation

HRID 85158 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[NH:13][C:12]2[CH:14]=[CH:15][CH:16]=[C:17]([C:18]([NH:20][C:21]3[N:26]=[CH:25][C:24]([CH2:27][N:28]4[CH2:33][CH2:32][N:31](C(OCC5C=CC=CC=5)=O)[CH2:30][CH2:29]4)=[CH:23][CH:22]=3)=[O:19])[C:11]=2[N:10]=1>CO.[Pd]>[N:28]1([CH2:27][C:24]2[CH:23]=[CH:22][C:21]([NH:20][C:18]([C:17]3[C:11]4[N:10]=[C:9]([C:4]5[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=5[C:2]([F:1])([F:44])[F:45])[NH:13][C:12]=4[CH:14]=[CH:15][CH:16]=3)=[O:19])=[N:26][CH:25]=2)[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1

Participants

4

Reactant 1

HCID 67201699benzyl 4-((6-(2-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamido)pyridin-3-yl)methyl)piperazine-1-carboxylate

Product 1

HCID 58279382N-(5-(piperazin-1-ylmethyl)pyridin-2-yl)-2-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamideYield 13%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of benzyl 4-((6-(2-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamido)pyridin-3-yl)methyl)piperazine-1-carboxylate (106; 280 mg, 0.46 mmol) in methanol (20 mL) was added Pd/C (0.1 g, 5% on carbon). The reaction mixture was stirred under 1 atm of H2 for 12 h and then filtered through a pad of Celite. The filtrate was concentrated under reduced pressure. The resulting residue was purified by chromatography (dichloromethane:methanol=5:1) to afford N-(5-(piperazin-1-ylmethyl)pyridin-2-yl)-2-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamide (Compound 621) (28.0 mg, 13%). MS (ESI) calcd for C25H23F3N6O: 480.19; found: 481 [M+H].

Workup

  1. filtrationfiltered through a pad of Celite
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customThe resulting residue was purified by chromatography (dichloromethane:methanol=5:1)

Sources & evidence

ORD record
ord-00545a856ccb47ff92b629121f36fd1e
Source dataset
uspto-grants-2014_09
Patent number
US08846947B2

Reaction notes

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