Trifluoroacetic acid → HCID 86708685, compound

HRID 921789Notes

Reaction equation

HRID 921789 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[C:14]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH:22]3[CH2:25][O:24][CH2:23]3)[CH2:18][CH2:17]2)=[CH:13][C:12]([C:26]#[N:27])=[CH:11][C:10]=1[NH:28][C:29]1[N:34]=[C:33]([N:35]([CH:45]2[CH2:47][CH2:46]2)CC2C=CC(OC)=CC=2)[C:32]2=[N:48][CH:49]=[C:50]([C:51]#[N:52])[N:31]2[N:30]=1.C1(OC)C=CC=CC=1>ClCCCl>[Cl:8][C:9]1[C:14]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH:22]3[CH2:25][O:24][CH2:23]3)[CH2:18][CH2:17]2)=[CH:13][C:12]([C:26]#[N:27])=[CH:11][C:10]=1[NH:28][C:29]1[N:34]=[C:33]([NH:35][CH:45]2[CH2:46][CH2:47]2)[C:32]2=[N:48][CH:49]=[C:50]([C:51]#[N:52])[N:31]2[N:30]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 867086842-((2-Chloro-5-cyano-3-((1-(oxetan-3-yl)piperidin-4-yl)oxy)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 86708685HCID 86708685, compoundYield 66.7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

TFA (25% in DCE, 2 ml, 6.49 mmol) was added to a solution of 2-((2-chloro-5-cyano-3-((1-(oxetan-3-yl)piperidin-4-yl)oxy)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (50 mg, 0.080 mmol) and anisole (0.035 ml, 0.319 mmol) in DCE (1 mL) and the reaction mixture was heated at 45° C. for 3 hours. Solvent was evaporated in vacuo and the residue was dried under vacuum overnight. The residue was washed with hexane (2×2 ml), dissolved in acetonitrile (2 ml) and 2N ammonia in methanol was added to give a suspension. Solvent was evaporated until a very small amount and the precipitate was collected by filtration. 2-((2-chloro-5-cyano-3-((1-(oxetan-3-yl)piperidin-4-yl)oxy)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (27 mg) was obtained as a white solid.

Workup

  1. customSolvent was evaporated in vacuo
  2. customthe residue was dried under vacuum overnight
  3. washThe residue was washed with hexane (2×2 ml)
  4. dissolutiondissolved in acetonitrile (2 ml)
  5. addition2N ammonia in methanol was added
  6. customto give a suspension
  7. customSolvent was evaporated until a very small amount
  8. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-8aeb85c822e24d3699db40d31d9362c5
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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