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Potassium Phosphate, Tribasic → 2-((1H-indol-5-yl)ethynyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine

HRID 340255
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 340255
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]#[C:11][C:12]3[CH:13]=[C:14](Cl)[C:15]([C:18]#[N:19])=[N:16][CH:17]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CC1(C)C(C)(C)OB([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[NH:35]C(=O)OC(C)(C)C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:52]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.C(O)CCC>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]#[C:11][C:12]3[CH:17]=[N:16][C:15]4[C:14]([CH:13]=3)=[C:31]3[CH:32]=[CH:33][C:34]([CH3:52])=[CH:29][C:30]3=[N:35][C:18]=4[NH2:19])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
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Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 2773231tert-Butyl (2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 668923115-((1H-indol-5-yl)ethynyl)-3-chloropicolinonitrile

Produkt 1

HCID 668930492-((1H-indol-5-yl)ethynyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 2631-ButanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a round bottom flask with refluxing condenser were added 5-((1H-indol-5-yl)ethynyl)-3-chloropicolinonitrile (from the previous step) (1 eq.), tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from Example 5/Step 2) (1.25 eq.), K3PO4 (2 eq.), tris(dibenzylideneacetone)dipalladium(0) (0.05 eq.), and 2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.1 eq.). n-Butanol and water (5:2, 0.2 M) were added, and the content were degassed (vacuum followed by nitrogen flush) for three times. The reaction mixture was stirred vigorously under nitrogen at 100° C. overnight in an oil bath. The content were cooled down and were taken up in 200 mL of water followed by extraction with methylene chloride. Combined organic layers were dried (Na2SO4) and concentrated. Flash chromatography (silica gel, 0-50% EtOAc in CH2Cl2) afforded the product 2-((1H-indol-5-yl)ethynyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine as a yellow solid.

Aufarbeitung

  1. temperatureTo a round bottom flask with refluxing condenser
  2. customthe content were degassed
  3. custom(vacuum followed by nitrogen flush) for three times
  4. temperatureThe content were cooled down
  5. extractionfollowed by extraction with methylene chloride
  6. dry with materialCombined organic layers were dried (Na2SO4)
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-62dd8a73ca4a49649ab2b576f3759f63
Quelldatensatz
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08895577B2

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