Trifluoroacetic acid → 2-((2-Chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921945Notes

Reaction equation

HRID 921945 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[C:14]([N:15]2[CH2:26][CH2:25][C:18]3([C:22](=[O:23])[N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:17][CH2:16]2)=[CH:13][C:12]([C:27]#[N:28])=[CH:11][C:10]=1[NH:29][C:30]1[N:35]=[C:34]([N:36]([CH:46]2[CH2:48][CH2:47]2)CC2C=CC(OC)=CC=2)[C:33]2=[N:49][CH:50]=[C:51]([C:52]#[N:53])[N:32]2[N:31]=1.C1(OC)C=CC=CC=1>ClCCCl>[Cl:8][C:9]1[C:14]([N:15]2[CH2:16][CH2:17][C:18]3([C:22](=[O:23])[N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:25][CH2:26]2)=[CH:13][C:12]([C:27]#[N:28])=[CH:11][C:10]=1[NH:29][C:30]1[N:35]=[C:34]([NH:36][CH:46]2[CH2:47][CH2:48]2)[C:33]2=[N:49][CH:50]=[C:51]([C:52]#[N:53])[N:32]2[N:31]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 899236352-((2-Chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 899228952-((2-Chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 43.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

TFA (0.417 mL, 5.41 mmol) was added to a solution of 2-((2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (50 mg, 0.078 mmol) and anisole (0.034 mL, 0.314 mmol) in DCE (1 mL) and the reaction mixture was heated at 60° C. for 1 hours. The solvent was removed in vacuo and the material azeotroped with toluene 3× to remove the excess TFA. 10 ml of 2N NH3 in MeOH was added, and the solution was stirred for 20 min. The solvent was removed in vacuo and the material was purified by prep-HPLC to give 2-((2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (17.4 mg).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe material azeotroped with toluene 3×
  3. customto remove the excess TFA
  4. addition10 ml of 2N NH3 in MeOH was added
  5. customThe solvent was removed in vacuo
  6. customthe material was purified by prep-HPLC

Sources & evidence

ORD record
ord-edc4f509439f47ccabf3357be74ce342
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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