Trifluoroacetic acid → HCID 86708689, compound

HRID 921794Notes

Reaction equation

HRID 921794 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[C:14]([O:15][CH:16]2[CH2:20][CH2:19][N:18]([CH:21]3[CH2:24][O:23][CH2:22]3)[CH2:17]2)=[CH:13][C:12]([C:25]#[N:26])=[CH:11][C:10]=1[NH:27][C:28]1[N:33]=[C:32]([N:34]([CH:44]2[CH2:46][CH2:45]2)CC2C=CC(OC)=CC=2)[C:31]2=[N:47][CH:48]=[C:49]([C:50]#[N:51])[N:30]2[N:29]=1.C1(OC)C=CC=CC=1>ClCCCl>[Cl:8][C:9]1[C:14]([O:15][CH:16]2[CH2:20][CH2:19][N:18]([CH:21]3[CH2:22][O:23][CH2:24]3)[CH2:17]2)=[CH:13][C:12]([C:25]#[N:26])=[CH:11][C:10]=1[NH:27][C:28]1[N:33]=[C:32]([NH:34][CH:44]2[CH2:45][CH2:46]2)[C:31]2=[N:47][CH:48]=[C:49]([C:50]#[N:51])[N:30]2[N:29]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86708691HCID 86708691, compound

Product 1

HCID 86708689HCID 86708689, compoundYield 72.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

TFA (25% in DCE, 2 ml, 26.0 mmol) was added to a solution of (+/−)-2-((2-chloro-5-cyano-3-((1-(oxetan-3-yl)pyrrolidin-3-yl)oxy)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (38 mg, 0.062 mmol) and anisole (0.027 ml, 0.248 mmol) in DCE (1 mL) and the reaction mixture was heated at 60° C. for 2 hours. Solvent was evaporated in vacuo and the residue was dried under vacuum overnight. The crude was trituated with hexane 3×1 ml, dissolved in acetonitrile and neutralized with 2N ammonia in methanol. Solvent was evaporated to give a solid which was purified by flash chromatography on silica gel using an automated ISCO system (24 g gold column, eluting with 1-4% 2 N ammonia in methanol/dichloromethane). (+/−)-2-((2-chloro-5-cyano-3-((1-(oxetan-3-yl)pyrrolidin-3-yl)oxy)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (22 mg) was obtained as a white solid.

Workup

  1. customSolvent was evaporated in vacuo
  2. customthe residue was dried under vacuum overnight
  3. dissolutiondissolved in acetonitrile and neutralized with 2N ammonia in methanol
  4. customSolvent was evaporated
  5. customto give a solid which
  6. customwas purified by flash chromatography on silica gel using
  7. washan automated ISCO system (24 g gold column, eluting with 1-4% 2 N ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-535b762fc23b4135a1d0fb4b99cc7ffa
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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