Sodium Chloride → 3-(2-Chloro-6,7-dimethoxyquinazolin-4-yl)phenylamine

HRID 41491

Reaktionsgleichung

Reaktionsgleichung von HRID 41491
C(=O)([O-])[O-].[Na+].[Na+].O.[NH2:8][C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[CH:13][CH:14]=1.[Cl:18][C:19]1[N:28]=[C:27](Cl)[C:26]2[C:21](=[CH:22][C:23]([O:32][CH3:33])=[C:24]([O:30][CH3:31])[CH:25]=2)[N:20]=1.[Cl-].[Na+]>O1CCCC1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[Cl:18][C:19]1[N:28]=[C:27]([C:13]2[CH:14]=[C:9]([NH2:8])[CH:10]=[CH:11][CH:12]=2)[C:26]2[C:21](=[CH:22][C:23]([O:32][CH3:33])=[C:24]([O:30][CH3:31])[CH:25]=2)[N:20]=1

Komponenten

9

Edukt 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 5203272,4-Dichloro-6,7-dimethoxyquinazolineHCID 143894233-Aminophenylboronic acid monohydrate

Produkt 1

HCID 576095393-(2-Chloro-6,7-dimethoxyquinazolin-4-yl)phenylamineAusbeute 99,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11776TriphenylphosphineKatalysatorHCID 24290Palladium ChlorideKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To 634 g of sodium carbonate (5.98 mol) was added 2.91 kg of water under a nitrogen atmosphere, followed by stirring for dissolution. To the solution were added 3.0 L of tetrahydrofuran, 431 g of 3-aminophenyl boronic acid monohydrate (2.78 mol), 30.4 g of triphenylphosphine (0.116 mol) and 26.0 g of dichloropalladium (0.116 mol) in this order. To the mixture was dropwise added a solution of 2,4-dichloro-6,7-dimethoxyquinazoline (600 g; 2.32 mol) in tetrahydrofuran (12.0 L) over 2 hours while stirring at 60° C., followed by stirring at the same temperature for 16 hours. To the mixture were added 3.0 kg of a 5% sodium chloride solution and 12.0 L of tetrahydrofuran in this order, and the mixture was stirred at 50° C. for 1 hour and allowed to cool down to 25° C. The mixture was filtered through celite to remove the insoluble matter, and the filtrate was transferred to separatory funnel and the organic layer was separated. To the organic layer were added 150 g of anhydrous magnesium sulfate and 60.0 g of activated carbon, and the mixture was stirred at 50° C. for 1 hour and allowed to cool down to 25° C. The mixture was filtered through celite to remove the insoluble matter, and the filtrate was concentrated under reduced pressure. To the residue was added 6.0 L of water, and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were filtered, and the crystals were dried at 50° C. under reduced pressure to yield 730 g of a target product. Yield: 62.1%

Aufarbeitung

  1. stirringwhile stirring at 60° C.
  2. stirringby stirring at the same temperature for 16 hours
  3. stirringthe mixture was stirred at 50° C. for 1 hour
  4. filtrationThe mixture was filtered through celite
  5. customto remove the insoluble matter
  6. customthe filtrate was transferred to separatory funnel
  7. customthe organic layer was separated
  8. additionTo the organic layer were added 150 g of anhydrous magnesium sulfate and 60.0 g of activated carbon
  9. stirringthe mixture was stirred at 50° C. for 1 hour
  10. temperatureto cool down to 25° C
  11. filtrationThe mixture was filtered through celite
  12. customto remove the insoluble matter
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. additionTo the residue was added 6.0 L of water
  15. stirringthe mixture was stirred at room temperature for 1 hour
  16. filtrationThe precipitated crystals were filtered
  17. customthe crystals were dried at 50° C. under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-0e54c180fe5542ff8936b77f22a1b8ab
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530654B2

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