Trifluoroacetic acid → HCID 86708563, compound

HRID 921692Notes

Reaction equation

HRID 921692 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][N:11]([CH:14]3[CH2:17][O:16][CH2:15]3)[CH:10]([CH2:18][F:19])[CH2:9]2)=[CH:6][C:5]([C:20]#[N:21])=[CH:4][C:3]=1[NH:22][C:23]1[N:28]=[C:27]([N:29]([CH:39]2[CH2:41][CH2:40]2)CC2C=CC(OC)=CC=2)[C:26]2=[N:42][CH:43]=[C:44]([C:45]#[N:46])[N:25]2[N:24]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][N:11]([CH:14]3[CH2:15][O:16][CH2:17]3)[CH:10]([CH2:18][F:19])[CH2:9]2)=[CH:6][C:5]([C:20]#[N:21])=[CH:4][C:3]=1[NH:22][C:23]1[N:28]=[C:27]([NH:29][CH:39]2[CH2:40][CH2:41]2)[C:26]2=[N:42][CH:43]=[C:44]([C:45]#[N:46])[N:25]2[N:24]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid3×HCID 7519AnisoleHCID 86708564HCID 86708564, compound

Product 1

HCID 86708563HCID 86708563, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

(+/−)2-((2-chloro-5-cyano-3-(3-(fluoromethyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (131 mg, 0.204 mmol) was taken up in DCE (2 mL) and anisole (0.067 mL, 0.611 mmol) was added, followed by TFA (0.314 mL, 4.07 mmol). The reaction was stirred at room temperature overnight. An additional 40 eq. of TFA was added and the reaction was stirred for 2 h, then an additional 60 eq. of TFA and was added, followed by stirring for 1 h. The solvent was removed in vacuo and the material was dissolved in MeOH. The material was loaded onto an SCX column (5 g, benzenesulfonic acid) and the column was flushed with MeOH, then 1:1 DCM/7N NH3 in MeOH to obtain the product. The solvent was removed in vacuo and the material was dissolved in DMF. A solid precipitated out, which was collected by vacuum filtration and rinsed with MeOH. The solid was suspended in 1 ml of 1:1 CH3CN/H2O and lyophilized overnight. (+/−)2-((2-chloro-5-cyano-3-(3-(fluoromethyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile was obtained as a beige solid.

Workup

  1. stirringthe reaction was stirred for 2 h
  2. stirringby stirring for 1 h
  3. customThe solvent was removed in vacuo
  4. dissolutionthe material was dissolved in MeOH
  5. customthe column was flushed with MeOH
  6. custom1:1 DCM/7N NH3 in MeOH to obtain the product
  7. customThe solvent was removed in vacuo
  8. dissolutionthe material was dissolved in DMF
  9. customA solid precipitated out
  10. filtrationwhich was collected by vacuum filtration
  11. washrinsed with MeOH
  12. waitlyophilized overnight

Sources & evidence

ORD record
ord-4ef40656511a4e76914763b69b0f4105
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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