Cesium carbonate → HCID 89923142, 화합물

HRID 921828노트

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HRID 921828 반응식
[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

참가 물질

6

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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

생성물 1

HCID 89923142HCID 89923142, 화합물수율 87.9%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-7dd33c89d98849ca966f0e4db5c437ec
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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