Trifluoroacetic acid → 2-((2-Chloro-5-cyano-3-(4-hydroxybutan-2-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921854Notes

Reaction equation

[Cl:1][C:2]1[C:7]([CH:8]([CH2:10][CH2:11][OH:12])[CH3:9])=[CH:6][C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([N:22]([CH:32]2[CH2:34][CH2:33]2)CC2C=CC(OC)=CC=2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:1][C:2]1[C:7]([CH:8]([CH2:10][CH2:11][OH:12])[CH3:9])=[CH:6][C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([NH:22][CH:32]2[CH2:33][CH2:34]2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1

Participants

Conditions

Temperature: 50 °C

Procedure

2-((2-chloro-5-cyano-3-(4-hydroxybutan-2-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (25 mg, 0.046 mmol) was taken up in DCE (0.5 mL) and anisole (10.06 μl, 0.092 mmol) was added, followed by TFA (0.142 mL, 1.842 mmol). The reaction was heated at 50° C. for 2 h. The solvent was removed in vacuo and the material dissolved in 2N NH3 in MeOH. The solution was stirred for 10 min to cleave the ester, and the solvent was removed in vacuo. The material purified by preparative HPLC. 2-((2-chloro-5-cyano-3-(4-hydroxybutan-2-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (10.7 mg) was obtained.

Workup

customThe solvent was removed in vacuo
dissolutionthe material dissolved in 2N NH3 in MeOH
customthe solvent was removed in vacuo
customThe material purified by preparative HPLC

Sources & evidence

ORD record: ord-b4c71fcaae01475e97ef6a36d12f2cbd
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273057B2

Reaction notes

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