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

HRID 1259123
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Reaktionsgleichung

Reaktionsgleichung von HRID 1259123
[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-c3316bd0eeb34ec78e97b3687ad684d4
Quelldatensatz
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08466167B2

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