Cesium carbonate → HCID 89923142, Verbindung

HRID 921828Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921828
[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

Komponenten

6

Edukt 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

Produkt 1

HCID 89923142HCID 89923142, VerbindungAusbeute 87,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-7dd33c89d98849ca966f0e4db5c437ec
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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