Cesium carbonate → (S)-2-(1-((6-Amino-5-(3-(difluoromethyl)-5-hydroxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

HRID 1052771Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1052771
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1Br.[F:29][CH:30]([F:47])[C:31]1[CH:32]=[C:33]([OH:46])[CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1[C:35]1[CH:34]=[C:33]([OH:46])[CH:32]=[C:31]([CH:30]([F:47])[F:29])[CH:36]=1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 901024333-(Difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 118433733HCID 118433733, Verbindung

Produkt 1

HCID 118433876(S)-2-(1-((6-Amino-5-(3-(difluoromethyl)-5-hydroxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-oneAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of (S)-2-(1-((6-amino-5-bromopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (65 mg, 0.15 mmol) were added 3-(difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (91 mg, 0.15 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (12 mg, 0.01 mmol) and 147 μl of a 2M aqueous solution of cesium carbonate in dioxane (2 ml). The mixture was stirred under argon atmosphere at 100° C. for 18 hours and then diluted with ethyl acetate. The resulting solution was washed with water and brine, dried over magnesium sulphate, filtered and the solvents were removed under reduced pressure. The product was purified by reverse phase using SP1® Purification System to give 48 mg (64% yield) as a solid. Purity 99%.

Aufarbeitung

  1. washThe resulting solution was washed with water and brine
  2. dry with materialdried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. customThe product was purified by reverse phase
  6. custom® Purification System
  7. customto give 48 mg (64% yield) as a solid

Quellen und Nachweise

ORD-Eintrag
ord-da3687c8e80f469fbd09aeb3eeee4c77
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388189B2

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