Cesium carbonate → HCID 86708696, Verbindung

HRID 921798Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921798
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]([O:36][CH:37]2[CH2:42][CH2:41][N:40]([C:43]3([CH3:47])[CH2:46][O:45][CH2:44]3)[CH2:39][CH2:38]2)[C:34]=1[Cl:35])[C:30]#[N:31].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.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]([O:36][CH:37]2[CH2:42][CH2:41][N:40]([C:43]3([CH3:47])[CH2:44][O:45][CH2:46]3)[CH2:39][CH2:38]2)=[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[CH2:19][CH2:20]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

8

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile2×HCID 86708695HCID 86708695, Verbindung

Produkt 1

HCID 86708696HCID 86708696, VerbindungAusbeute 40,8 %

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 (Intermediate 9) (47.4 mg, 0.134 mmol), 3-amino-4-chloro-5-((1-(3-methyloxetan-3-yl)piperidin-4-yl)oxy)benzonitrile (43 mg, 0.134 mmol), palladium(II) acetate (7.95 mg, 0.035 mmol), xantphos (7.73 mg, 0.013 mmol), DPPF (7.41 mg, 0.013 mmol) and cesium carbonate (113 mg, 0.347 mmol) in dioxane (2 ml) was evacuated and back filled with nitrogen three time and was heated at 80° C. for 6 h. The reaction mixture was filtered through a pad of celite, the filtrate was concentrated and the crude was purified by prep-HPLC. 2-((2-chloro-5-cyano-3-((1-(3-methyloxetan-3-yl)piperidin-4-yl)oxy)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (35 mg) was obtained.

Aufarbeitung

  1. customwas evacuated
  2. additionback filled with nitrogen three time
  3. filtrationThe reaction mixture was filtered through a pad of celite
  4. concentrationthe filtrate was concentrated
  5. customthe crude was purified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-014cb35f233649fca1b2f77d94852803
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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