Sodium Iodide → 3-((4-(4-(3-Cyclobutylureido)benzoyl)piperazin-1-yl)methyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamide

HRID 1878416Notes

Reaction equation

HRID 1878416 reaction equation
[CH:1]1([NH:5][C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:10]=2)=[O:7])[CH2:4][CH2:3][CH2:2]1.Cl[CH2:24][C:25]1[CH:26]=[C:27]([CH:38]=[CH:39][CH:40]=1)[C:28]([NH:30][C:31]([CH3:37])([CH3:36])[C:32]([F:35])([F:34])[F:33])=[O:29].C(N(CC)CC)C.[I-].[Na+]>O1CCCC1.C(OCC)(=O)C.C(#N)C>[CH:1]1([NH:5][C:6](=[O:7])[NH:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]([N:17]3[CH2:18][CH2:19][N:20]([CH2:24][C:25]4[CH:26]=[C:27]([CH:38]=[CH:39][CH:40]=4)[C:28]([NH:30][C:31]([CH3:37])([CH3:36])[C:32]([F:33])([F:35])[F:34])=[O:29])[CH2:21][CH2:22]3)=[O:16])=[CH:13][CH:14]=2)[CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 579175741-Cyclobutyl-3-(4-(piperazine-carbonyl)phenyl)ureaHCID 668783493-(chloromethyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamide

Product 1

HCID 579176613-((4-(4-(3-Cyclobutylureido)benzoyl)piperazin-1-yl)methyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamideYield 90%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 1-cyclobutyl-3-(4-(piperazine-1-carbonyl)phenyl)urea (0.165 mmol, 50 mg) in tetrahydrofuran (1654 μl) was added 3-(chloromethyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamide (0.182 mmol, 50.9 mg) and triethylamine (0.496 mmol, 69.1 μl, 50.2 mg). The reaction was heated to reflux and stirred for 30 minutes then acetonitrile (0.5 mL) and sodium iodide (catalytic amount) were added. After 3 hours stirring, ethyl acetate was added and the organic mixture was washed with water and saturated sodium chloride. The organic phase was dried with sodium sulfate, filtered and concentrated under reduced pressure. This material was lyophilised to give the title compound (81 mg). MS (ESI) m/z 546.5 [M+H]+

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux
  3. stirringAfter 3 hours stirring
  4. washthe organic mixture was washed with water and saturated sodium chloride
  5. dry with materialThe organic phase was dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4db7968fd61a4cbba332ab86629ee934
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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