(Trifluoromethyl)trimethylsilane → (+/-)-2-((2-Chloro-5-cyano-3-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921900

Reaction equation

HRID 921900 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[F:19][C:20]([Si](C)(C)C)([F:22])[F:21].[Cl:27][C:28]1[C:33]([CH:34]=[O:35])=[CH:32][C:31]([C:36]#[N:37])=[CH:30][C:29]=1[NH:38][C:39]1[N:44]=[C:43]([NH:45][CH:46]2[CH2:48][CH2:47]2)[C:42]2=[N:49][CH:50]=[C:51]([C:52]#[N:53])[N:41]2[N:40]=1>C1COCC1>[Cl:27][C:28]1[C:33]([CH:34]([OH:35])[C:20]([F:22])([F:21])[F:19])=[CH:32][C:31]([C:36]#[N:37])=[CH:30][C:29]=1[NH:38][C:39]1[N:44]=[C:43]([NH:45][CH:46]2[CH2:48][CH2:47]2)[C:42]2=[N:49][CH:50]=[C:51]([C:52]#[N:53])[N:41]2[N:40]=1

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 867086482-((2-Chloro-5-cyano-3-formylphenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 89934088(+/-)-2-((2-Chloro-5-cyano-3-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 17.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

TBAF (1 M in THF, 0.026 mL, 0.026 mmol) was added to a suspension of (trifluoromethyl)trimethylsilane (2 M solution in THF, 0.079 mL, 0.16 mmol) and 2-((2-chloro-5-cyano-3-formylphenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (20 mg, 0.053 mmol) in dry THF (1 mL) under nitrogen in an ice bath. The bath was removed and the reaction was left stirring at room temperature overnight. Aqueous 1 N HCl was added and the reaction was left stirring for 20 min. This was neutralized with 1.3 N potassium phosphate buffer and extracted three times with EtOAc. The organic extracts were washed with brine and dried with sodium sulfate. Radial silica gel chromatography eluting with DCM containing 0 to 15% EtOAc afforded the title compound (4.1 mg) as oil.

Workup

  1. customThe bath was removed
  2. waitthe reaction was left
  3. additionAqueous 1 N HCl was added
  4. waitthe reaction was left
  5. stirringstirring for 20 min
  6. extractionextracted three times with EtOAc
  7. washThe organic extracts were washed with brine
  8. dry with materialdried with sodium sulfate
  9. washRadial silica gel chromatography eluting with DCM containing 0 to 15% EtOAc

Sources & evidence

ORD record
ord-b23867537013472ebed78883b6eab118
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Linked notes

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