Pyridine → (S)-2-(1-((5-(1-(3-Amino-5-methoxyphenyl)-1H-pyrazol-3-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

HRID 1052645Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1052645
[NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[C:14]3[C:13]([NH:15][C@H:16]([C:18]4[N:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[C:22](=[O:30])[C:21]5=[C:31]([CH3:34])[CH:32]=[CH:33][N:20]5[N:19]=4)[CH3:17])=[N:12][CH:11]=[N:10][C:9]=3[N:8]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[CH:7]=2)=[N:2]1.[CH3:43][O:44][C:45]1[CH:46]=[C:47]([CH:49]=[C:50](B2OC(C)(C)C(C)(C)O2)[CH:51]=1)[NH2:48].N1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[NH2:48][C:47]1[CH:49]=[C:50]([N:1]2[CH:5]=[CH:4][C:3]([C:6]3[C:14]4[C:13]([NH:15][C@H:16]([C:18]5[N:23]([C:24]6[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=6)[C:22](=[O:30])[C:21]6=[C:31]([CH3:34])[CH:32]=[CH:33][N:20]6[N:19]=5)[CH3:17])=[N:12][CH:11]=[N:10][C:9]=4[N:8]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:40])([CH3:42])[CH3:41])[CH:7]=3)=[N:2]2)[CH:51]=[C:45]([O:44][CH3:43])[CH:46]=1

Komponenten

6

Edukt 4

HCID 1049Pyridine2×HCID 11430Potassium CarbonateHCID 901026273-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamineHCID 178428095HCID 178428095, Verbindung

Produkt 1

HCID 131736246(S)-2-(1-((5-(1-(3-Amino-5-methoxyphenyl)-1H-pyrazol-3-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-oneAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(S)-2-(1-((5-(1H-Pyrazol-3-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (67 mg, 0.12 mmol) was treated with 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (57 mg, 0.23 mmol), Cu(AcO)2 (32 mg, 0.18 mmol) and pyridine (20 μl, 0.25 mmol) in DMF (1.5 ml). The reaction mixture was submitted at vacuum-argon cycles and stirred at 100° C. under microwave conditions for 2 h. More pyridine and Cu(AcO)2 were added, and the reaction mixture stirred at 100° C. until the reaction was over. The solvent was cooled at room temperature and poured into ice-water, basified with potassium carbonate and extracted with ethyl acetate (×3). The organic phase was successively washed with water and brine, dried over magnesium sulfate, filtered and the solvent evaporated under reduced pressure. The residue (15.3 mg, 14% yield, 75% purity) was used in the next synthetic step without further purification.

Aufarbeitung

  1. stirringthe reaction mixture stirred at 100° C. until the reaction
  2. temperatureThe solvent was cooled at room temperature
  3. extractionextracted with ethyl acetate (×3)
  4. washThe organic phase was successively washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customThe residue (15.3 mg, 14% yield, 75% purity) was used in the next synthetic step without further purification

Quellen und Nachweise

ORD-Eintrag
ord-39da8c435435410184be6ca6dd3e9759
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388189B2

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