Hydrochloric Acid → HCID 178483083, Verbindung

HRID 1984903Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1984903
C1OCCOCCOCCOCCOCCOC1.[Br:19][C:20]1[CH:25]=[CH:24][C:23](I)=[C:22]([O:27][C:28]([F:31])([F:30])[F:29])[CH:21]=1.[NH2:32][C@@H:33]1[CH2:38][CH2:37][C@H:36]([NH:39][C:40]2[N:49]=[C:48]([N:50]([CH2:53]C)[CH2:51]C)[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[N:41]=2)[CH2:35][CH2:34]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[ClH:107]>CCOCC.CCOC(C)=O.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].C1COCC1>[ClH:107].[ClH:107].[Br:19][C:20]1[CH:25]=[CH:24][C:23]([NH:32][C@@H:33]2[CH2:34][CH2:35][C@H:36]([NH:39][C:40]3[N:49]=[C:48]([N:50]([CH3:53])[CH3:51])[C:47]4[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=4)[N:41]=3)[CH2:37][CH2:38]2)=[C:22]([O:27][C:28]([F:31])([F:30])[F:29])[CH:21]=1

Komponenten

11

Edukt 6

HCID 313Hydrochloric AcidHCID 2855718-Crown-6HCID 634876Binap, (A+-)-HCID 27364224-Bromo-2-(trifluoromethoxy)iodobenzeneHCID 23676156Sodium t-butoxideHCID 178463885HCID 178463885, Verbindung

Produkt 1

HCID 178483083HCID 178483083, VerbindungAusbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a glass flask were added 18-crown-6 (647 mg, 2.45 mmol), 4-Bromo-1-iodo-2-trifluoromethoxy-benzene (770 mg, 2.10 mmol), cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step C of example 9 (500 mg, 1.75 mmol), sodium tert-butoxide (235 mg, 2.45 mmol), tris(dibenzylideneacetone)dipalladium (160 mg, 0.175 mmol), (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (160 mg, 0.175 mmol) and THF (3.5 mL). The reaction mixture was stirred at reflux 18 hr. The mixture was filtered through a pad of celite, concentrated, and purified by flash chromatography (NH-silica gel, 33% EtOAc in hexane) to give a pale yellow oil. To a solution of above oil in Et2O (2 mL) was added 4 M hydrogen chloride in EtOAc (0.3 mL). The mixture was stirred at ambient temperature for 30 min and concentrated. A solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 15 min. The precipitate was collected by filtration, washed with Et2O, and dried under reduced pressure to give cis-N2-[4-(4-bromo-2-trifluoromethoxy-phenylamino)-cyclohexyl]-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride (189 mg, 18%) as a white solid.

Aufarbeitung

  1. temperatureat reflux 18 hr
  2. filtrationThe mixture was filtered through a pad of celite
  3. concentrationconcentrated
  4. custompurified by flash chromatography (NH-silica gel, 33% EtOAc in hexane)
  5. customto give a pale yellow oil
  6. stirringThe mixture was stirred at ambient temperature for 30 min
  7. concentrationconcentrated
  8. stirringA solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 15 min
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with Et2O
  11. customdried under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-163edc018bd04e6282360fe77f26dcbb
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07544690B2

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