Trifluoroacetic acid → 4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-1-(2,2-difluoroethyl)-N,N-dimethylpiperazine-2-carboxamide

HRID 921829ノート

反応式

HRID 921829 の反応式
[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15]([CH:25]3[CH2:27][CH2:26]3)CC3C=CC(OC)=CC=3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][N:38]([CH2:41][CH:42]([F:44])[F:43])[CH:37]([C:45]([N:47]([CH3:49])[CH3:48])=[O:46])[CH2:36]1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH:25]3[CH2:26][CH2:27]3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][N:38]([CH2:41][CH:42]([F:43])[F:44])[CH:37]([C:45]([N:47]([CH3:49])[CH3:48])=[O:46])[CH2:36]1

参加物

5

反応物 3

HCID 6422Trifluoroacetic acid3 回HCID 7519AnisoleHCID 89923142HCID 89923142、化合物

生成物 1

HCID 899227344-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-1-(2,2-difluoroethyl)-N,N-dimethylpiperazine-2-carboxamide収率 65.3%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-1-(2,2-difluoroethyl)-N,N-dimethylpiperazine-2-carboxamide (37 mg, 0.054 mmol) was taken up in DCE (0.5 mL) and anisole (0.029 mL, 0.268 mmol) was added, followed by TFA (0.124 mL, 1.608 mmol). The reaction was stirred at room temperature overnight. LCMS indicates mostly SM is present. An additional 30 eq. of TFA was added and the reaction was heated at 50° C. After 4 h, an additional 30 eq. of TFA was added, and the reaction heated for 1.5 h. The solvent was removed in vacuo and the material azeotroped 2× with toluene, then triturated with Et2O to remove anisole. The material was purified by preparative HPLC to provide 4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-1-(2,2-difluoroethyl)-N,N-dimethylpiperazine-2-carboxamide (20.1 mg) as a yellow solid.

後処理

  1. temperaturethe reaction was heated at 50° C
  2. waitAfter 4 h
  3. temperaturethe reaction heated for 1.5 h
  4. customThe solvent was removed in vacuo
  5. customthe material azeotroped 2× with toluene
  6. customtriturated with Et2O
  7. customto remove anisole
  8. customThe material was purified by preparative HPLC

出典と根拠

ORDレコード
ord-d6b685fbb73540758ab13b1626976335
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…