Cesium carbonate → 2-((2-Chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921869Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921869
Cl[C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1.[NH2:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][C:37]2=[O:43])[C:34]=1[Cl:35])[C:30]#[N:31].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[Cl:35][C:34]1[C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][C:37]2=[O:43])=[CH:32][C:29]([C:30]#[N:31])=[CH:28][C:27]=1[NH:26][C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)[CH2:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileHCID 89922410HCID 89922410, Verbindung

Produkt 1

HCID 899225422-((2-Chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileAusbeute 97,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (40 mg, 0.113 mmol), 3-amino-4-chloro-5-(4-methyl-2-oxopiperazin-1-yl)benzonitrile (28 mg, 0.106 mmol), palladium(ii) acetate (12 mg, 0.053 mmol), XANTPIIOS (12 mg, 0.021 nmmol), DPPF (12 mg, 0.022 mmol) and cesium carbonate (90 mg, 0.275 mmol) in Dioxane (1.5 mL) was evacuated and back filled with nitrogen three time and was heated at 80° C. for 3 h. LC-MS showed reaction was complete. The reaction mixture was filtered through a pad of Celite, rinsed with EtOAc and the filtrate was concentrated and purification via flash chromatography (0-70% EtOAc in Hexane, 24 g) gave 2-((2-chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (60 mg) as a light oil.

Aufarbeitung

  1. customwas evacuated
  2. additionback filled with nitrogen three time
  3. customreaction
  4. filtrationThe reaction mixture was filtered through a pad of Celite
  5. washrinsed with EtOAc
  6. concentrationthe filtrate was concentrated
  7. custompurification via flash chromatography (0-70% EtOAc in Hexane, 24 g)

Quellen und Nachweise

ORD-Eintrag
ord-3c524a5e4e2a497ca5f2f766cd85c278
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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