Water → 7-(5-Fluoro-4-methylpyridin-3-yl)isoquinolin-3-amine

HRID 468934Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 468934
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:7]=1[CH3:8].Br[C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[C:24]([NH2:29])[N:25]=[CH:26]2)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C(#N)C.O>C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:1][C:2]1[C:7]([CH3:8])=[C:6]([C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[C:24]([NH2:29])[N:25]=[CH:26]3)=[CH:21][CH:20]=2)[CH:5]=[N:4][CH:3]=1

Komponenten

8

Edukt 5

HCID 962WaterHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 529877577-Bromoisoquinolin-3-amineHCID 679764003-Fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Produkt 1

HCID 679748447-(5-Fluoro-4-methylpyridin-3-yl)isoquinolin-3-amineAusbeute 83,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)KatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (261 mg; 0.7706 mmol), 7-bromoisoquinolin-3-amine (233.1 mg; 1.045 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (52.8 mg; 0.0746 mmol), potassium carbonate (338 mg; 2.44566 mmol), acetonitrile (3.0 mL; 57 mmol) and water (0.30 mL; 17 mmol) was heated at 120° C. for 40 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-5% methanol in dichloromethane) to yield 162.4 mg (83%) of the title compound. LCMS (ESI): M+H=254.2; 1H NMR (400 MHz, DMSO) δ 8.88 (s, 1H), 8.50 (s, 1H), 8.37 (s, 1H), 7.86 (s, 1H), 7.63 (d, J=8.6 Hz, 1H), 7.51 (dd, J=8.6, 1.6 Hz, 1H), 6.67 (s, 1H), 6.04 (s, 2H), 2.25 (d, J=2.0 Hz, 3H).

Aufarbeitung

  1. washwashed with water and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude product was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-5% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-6eeb8ecb78ed45bc8159d582b0f8525a
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623889B2

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