Trifluoroacetic acid → 2-((2-chloro-5-cyano-3-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921935Notes

Reaction equation

HRID 921935 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][C@@H:12]3[CH2:14][C@H:9]2[CH2:10][N:11]3[CH3:15])=[CH:6][C:5]([C:16]#[N:17])=[CH:4][C:3]=1[NH:18][C:19]1[N:24]=[C:23]([N:25](CC)[CH2:26][C:27]2C=CC(OC)=CC=2)[C:22]2=[N:37][CH:38]=[C:39]([C:40]#[N:41])[N:21]2[N:20]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)CCl>[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][C@@H:12]3[CH2:14][C@H:9]2[CH2:10][N:11]3[CH3:15])=[CH:6][C:5]([C:16]#[N:17])=[CH:4][C:3]=1[NH:18][C:19]1[N:24]=[C:23]([NH:25][CH2:26][CH3:27])[C:22]2=[N:37][CH:38]=[C:39]([C:40]#[N:41])[N:21]2[N:20]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 1182534392-((2-chloro-5-cyano-3-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)amino)-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 899232632-((2-chloro-5-cyano-3-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 58.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

2-((2-chloro-5-cyano-3-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)amino)-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (163 mg, 0.186 mmol) (crude, <=0.190 mmol) was dissolved in ClCH2CH2Cl (10 mL). Anisole (1 ml, 9.15 mmol) and TFA (2 ml, 26.0 mmol) were added and the mixture stirred at room temperature for 3 hours. The reaction mixture was evaporated to a sticky oil, dissolved in DMSO and purified by prep HPLC to give 48.5 mg of 2-((2-chloro-5-cyano-3-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Workup

  1. customThe reaction mixture was evaporated to a sticky oil
  2. dissolutiondissolved in DMSO
  3. custompurified by prep HPLC

Sources & evidence

ORD record
ord-1f7c7b032f2640fa9e28d7c7fb6fc05c
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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