Sodium Carbonate → 4-(7-chloro-1H-indazol-5-yl)-isoquinoline

HRID 1983916Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1983916
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](B(O)O)=[CH:3][N:2]=1.Br[C:15]1[CH:16]=[C:17]2[C:21](=[C:22]([Cl:24])[CH:23]=1)[NH:20][N:19]=[CH:18]2.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(COC)OC>[Cl:24][C:22]1[CH:23]=[C:15]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=[N:2][CH:3]=2)[CH:16]=[C:17]2[C:21]=1[NH:20][N:19]=[CH:18]2

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 3761204Isoquinoline-4-boronic acidHCID 211021945-Bromo-7-chloro-1H-indazole

Produkt 1

HCID 689979964-(7-chloro-1H-indazol-5-yl)-isoquinolineAusbeute 72,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture of isoquinolin-4-ylboronic acid (1.00 g, 5.78 mmol), 5-bromo-7-chloro-1H-indazole (892 mg, 3.85 mmol), 2.0 M sodium carbonate (3.85 mL, 7.71 mmol) and dimethoxyethane was degassed with argon. Tetrakis(triphenylphosphine)palladium(0) (233 mg, 0.193 mmol) was added, the mixture degassed again with argon, then heated to 85° C. for 24 hours. The reaction was cooled and partitioned between ethyl acetate and water, the organic layer washed with and dried with sodium sulfate. The solvent was removed under vacuum and the residue purified by column chromatography (9/1 to 6/4 hexanes/ethyl acetate gradient) to give 4-(7-chloro-1H-indazol-5-yl)-isoquinoline (777 mg, 72%): 1H NMR (300 MHz, CDCl3) δ 10.52 (s, 1H) 9.31 (s, 1H), 8.53 (s, 1H), 8.22 (s, 1H), 8.09 (dd, J=7.4, 1.62 Hz, 1H), 7.28 (dd, J=7.4, 1.2 Hz, 1H), 7.87 (d, J=9.0 Hz, 1H), 7.81 (d, J=1.2 Hz, 1H), 7.72-7.64 (m, 2H), 7.57 (d, J=1.3 Hz, 1H).

Aufarbeitung

  1. customwas degassed with argon
  2. customthe mixture degassed again with argon
  3. temperatureThe reaction was cooled
  4. custompartitioned between ethyl acetate and water
  5. washthe organic layer washed with and
  6. dry with materialdried with sodium sulfate
  7. customThe solvent was removed under vacuum
  8. customthe residue purified by column chromatography (9/1 to 6/4 hexanes/ethyl acetate gradient)

Quellen und Nachweise

ORD-Eintrag
ord-ea7fe082ffb1421db7d7a299cff7e091
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07541357B2

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