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

HRID 921667ノート

反応式

HRID 921667 の反応式
[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)[CH2:10][CH2:9]2)=[CH:6][C:5]([CH:18]([F:20])[F:19])=[CH:4][C:3]=1[NH:21][C:22]1[N:27]=[C:26]([N:28]([CH:38]2[CH2:40][CH2:39]2)CC2C=CC(OC)=CC=2)[C:25]2=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:24]2[N:23]=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[CH2:17][O:16][CH2:15]3)[CH2:10][CH2:9]2)=[CH:6][C:5]([CH:18]([F:19])[F:20])=[CH:4][C:3]=1[NH:21][C:22]1[N:27]=[C:26]([NH:28][CH:38]2[CH2:40][CH2:39]2)[C:25]2=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:24]2[N:23]=1

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 867085322-((2-Chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

生成物 1

HCID 867085332-((2-Chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile収率 26.2%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

反応条件

温度
40 °C

実験手順

2-((2-Chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (69 mg, 0.108 mmol) was dissolved in DCE (1 mL) at room temperature. Anisole (59.2 μl, 0.542 mmol) followed by 200 μL of TFA were added and the reaction was stirred at 40° C. overnight and concentrated. The residue was dissolved in MeOH and loaded onto a 1 g/6 mL Strata SCX ion exchange column, washing with CH3OH. The desired product was eluted with 7 N NH3—CH3OH, concentrated under a stream of N2. Column chromatography (12 g SiO2, 0 to 20% CH3OH—CH2Cl2 gradient elution) followed by trituration with ACN afforded 2-((2-chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (14.6 mg).

後処理

  1. additionwere added
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in MeOH
  4. washwashing with CH3OH
  5. washThe desired product was eluted with 7 N NH3—CH3OH
  6. concentrationconcentrated under a stream of N2
  7. washColumn chromatography (12 g SiO2, 0 to 20% CH3OH—CH2Cl2 gradient elution)

出典と根拠

ORDレコード
ord-37cdd36e0a34462ba9b1d79978901b24
出典データセット
uspto-grants-2016_03
特許番号
US09273057B2

反応ノート

読み込み中…