Water → 6-chloro-N5-(1-cyanocyclopropyl)-1-(prop-2-yn-1-yl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

HRID 514268Notes

Reaction equation

HRID 514268 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([NH:13][CH:14]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[C:15]([F:18])([F:17])[F:16])=[O:12])[NH:8]2)=[CH:4][C:3]=1[C:29]([NH:31][C:32]1([C:35]#[N:36])[CH2:34][CH2:33]1)=[O:30].[H-].[Na+].[CH2:39](Br)[C:40]#[CH:41].O>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([NH:13][CH:14]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:28])[F:27])[CH:20]=3)[C:15]([F:16])([F:18])[F:17])=[O:12])[N:8]2[CH2:41][C:40]#[CH:39])=[CH:4][C:3]=1[C:29]([NH:31][C:32]1([C:35]#[N:36])[CH2:34][CH2:33]1)=[O:30]

Participants

7

Reactant 4

HCID 962WaterHCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 867139856-chloro-N5-(1-cyanocyclopropyl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

Product 1

HCID 867139866-chloro-N5-(1-cyanocyclopropyl)-1-(prop-2-yn-1-yl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamideYield 50.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Chloro-N5-(1-cyanocyclopropyl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide (0.14 g, 0.26 mmol) was dissolved under argon at 0° C. in N,N-dimethylformamide (1 ml). Sodium hydride (60%; 0.079 g, 1.97 mmol) was added and the mixture was stirred while cooling with ice for 1.5 h. Subsequently, propargyl bromide (0.04 mg, 0.26 mmol) was added dropwise. The reaction mixture was thawed while stirring within 16 h. Water and ethyl acetate were added and the phases were separated. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue is purified by means of preparative HPLC (Kromasil100, C18 250×20; eluent: acetonitrile in water, gradient: 10-100%) to obtain 0.075 g (50% of theory) of 6-chloro-N5-(1-cyanocyclopropyl)-1-(prop-2-yn-1-yl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.

Workup

  1. temperaturewhile cooling with ice for 1.5 h
  2. stirringwhile stirring within 16 h
  3. customthe phases were separated
  4. washThe organic phase was washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue is purified by means of preparative HPLC (Kromasil100, C18 250×20

Sources & evidence

ORD record
ord-cb1a8edb08a04b5c8aacb742b2380e0f
Source dataset
uspto-grants-2015_08
Patent number
US09107411B2

Reaction notes

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