Isobutylamine → N-tert-Butyl-5-((4-(3-fluoro-4-(3-isobutylureido)benzoyl)piperazin-1-yl)methyl)furan-2-carboxamide

HRID 408858Notes

Reaction equation

HRID 408858 reaction equation
[NH2:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[O:19][C:18]([C:20]([NH:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][C:3]=1[F:29].C(N(CC)C(C)C)(C)C.ClC(O[C:44](=[O:50])OC(Cl)(Cl)Cl)(Cl)Cl.[CH3:51][CH:52]([CH3:55])[CH2:53][NH2:54]>ClCCl>[C:23]([NH:22][C:20]([C:18]1[O:19][C:15]([CH2:14][N:11]2[CH2:10][CH2:9][N:8]([C:6](=[O:7])[C:5]3[CH:27]=[CH:28][C:2]([NH:1][C:44]([NH:54][CH2:53][CH:52]([CH3:55])[CH3:51])=[O:50])=[C:3]([F:29])[CH:4]=3)[CH2:13][CH2:12]2)=[CH:16][CH:17]=1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 6558IsobutylamineHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 666615235-((4-(4-Amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylfuran-2-carboxamide

Product 1

HCID 46182138N-tert-Butyl-5-((4-(3-fluoro-4-(3-isobutylureido)benzoyl)piperazin-1-yl)methyl)furan-2-carboxamideYield 21.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-((4-(4-Amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylfuran-2-carboxamide (Example 3; 0.05 g, 0.124 mmol) and N,N-diisopropylethylamine (0.028 mL) were dissolved in dichloromethane (5 mL). Bis(trichloromethyl)carbonate (0.014 g, 0.046 mmol) was added dropwise and the reaction was left to stir for 30 minutes. N,N-diisopropylethylamine (0.094 mL) was added to the reaction followed by 2-methylpropan-1-amine (0.018 g, 0.248 mmol, 0.025 mL) and the reaction was stirred for a further 2 hours. The reaction mixture was washed with water and flushed through a hydrophobic frit. The organic phase was concentrated under vacuum and purified by basic reverse phase HPLC to afford the title compound (5 mg).

Workup

  1. waitthe reaction was left
  2. stirringthe reaction was stirred for a further 2 hours
  3. washThe reaction mixture was washed with water
  4. customflushed through a hydrophobic frit
  5. concentrationThe organic phase was concentrated under vacuum
  6. custompurified by basic reverse phase HPLC

Sources & evidence

ORD record
ord-f75fa8404add4a25bb32bcee93ef2dbd
Source dataset
uspto-grants-2014_06
Patent number
US08759352B2

Reaction notes

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