Cesium carbonate → HCID 89923142、化合物

HRID 921828ノート

反応式

HRID 921828 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)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=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][NH:38][CH:37]([C:41]([N:43]([CH3:45])[CH3:44])=[O:42])[CH2:36]1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:53][CH:54]([F:56])[F:55]>CN(C=O)C.CCOC(C)=O>[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)[CH2:16][C:17]3[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=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]([CH2:53][CH:54]([F:56])[F:55])[CH:37]([C:41]([N:43]([CH3:44])[CH3:45])=[O:42])[CH2:36]1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 1361862-Bromo-1,1-difluoroethaneHCID 899226614-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-N,N-dimethylpiperazine-2-carboxamide

生成物 1

HCID 89923142HCID 89923142、化合物収率 87.9%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

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)-N,N-dimethylpiperazine-2-carboxamide (38 mg, 0.061 mmol, Example 563D) was taken up in DMF (0.5 mL) and Cs2CO3 (39.5 mg, 0.121 mmol) and 2-bromo-1,1-difluoroethane (5.79 μl, 0.073 mmol) were added. The reaction was heated at 80° C. for 2 h. The reaction mixture was cooled to room temperature and diluted with EtOAc. The organic layer was extracted 2× with water and once with brine, then dried over Na2SO4, filtered, and concentrated. 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) was obtained as an orange glass. The crude material was taken onto the next step.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe organic layer was extracted 2× with water
  3. dry with materialonce with brine, then dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-7dd33c89d98849ca966f0e4db5c437ec
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…