Tetrabutylammonium Fluoride → 2-chloro-N-((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)acetamide

HRID 1430861Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1430861
[Si]([O:8][C@H:9]1[C@H:14]([NH:15][C:16](=[O:19])[CH2:17][Cl:18])[CH2:13][CH2:12][N:11]([C:20]2[CH:25]=[C:24]([C:26]#[N:27])[CH:23]=[C:22]([NH:28][C:29]3[N:34]=[C:33]([N:35]([CH:45]4[CH2:47][CH2:46]4)[CH2:36][C:37]4[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=4)[C:32]4=[N:48][CH:49]=[C:50]([C:51]#[N:52])[N:31]4[N:30]=3)[C:21]=2[Cl:53])[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:18][CH2:17][C:16]([NH:15][C@@H:14]1[CH2:13][CH2:12][N:11]([C:20]2[CH:25]=[C:24]([C:26]#[N:27])[CH:23]=[C:22]([NH:28][C:29]3[N:34]=[C:33]([N:35]([CH:45]4[CH2:47][CH2:46]4)[CH2:36][C:37]4[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=4)[C:32]4=[N:48][CH:49]=[C:50]([C:51]#[N:52])[N:31]4[N:30]=3)[C:21]=2[Cl:53])[CH2:10][C@H:9]1[OH:8])=[O:19]

Komponenten

4

Edukt 2

HCID 2724141Tetrabutylammonium FluorideHCID 86708552HCID 86708552, Verbindung

Produkt 1

HCID 867085532-chloro-N-((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)acetamideAusbeute 60,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To (+/−)-N-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)-2-chloroacetamide (43 mg, 0.055 mmol) in THF (1 mL) was added TBAF (1M in THF, 0.112 mL, 0.112 mmol) and the reaction solution was stirred at room temperature overnight. LCMS showed completion of reaction. Solvent was evaporated and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 0.5-4% methanol/dichloromethane) to give (+/−)-2-chloro-N-((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)acetamide (22 mg) as a white solid.

Aufarbeitung

  1. customcompletion of reaction
  2. customSolvent was evaporated
  3. customthe crude product was purified by flash chromatography on silica gel using
  4. washan automated ISCO system (24 g column, eluting with 0.5-4% methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-e5eddba66cbd44749711610f20664dd4
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940736B2

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