Hydrochloric Acid → HCID 178483090, Verbindung

HRID 1984909Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1984909
[ClH:1].Cl.Br[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][NH:12][C@@H:13]2[CH2:18][CH2:17][C@H:16]([NH:19][C:20]3[N:29]=[C:28]([N:30]([CH3:32])[CH3:31])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)[CH2:15][CH2:14]2)=[C:6]([O:33][C:34]([F:37])([F:36])[F:35])[CH:5]=1.Cl>CCO.CCOC(C)=O.[Pd]>[ClH:1].[ClH:1].[CH3:32][N:30]([CH3:31])[C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([NH:19][C@H:16]2[CH2:17][CH2:18][C@@H:13]([NH:12][CH2:11][CH2:10][C:7]3[CH:8]=[CH:9][CH:4]=[CH:5][C:6]=3[O:33][C:34]([F:37])([F:36])[F:35])[CH2:14][CH2:15]2)[N:29]=1

Komponenten

6

Edukt 2

HCID 313Hydrochloric AcidHCID 178483089HCID 178483089, Verbindung

Produkt 1

HCID 178483090HCID 178483090, VerbindungAusbeute 95,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 702EthanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

To a solution of cis-N2-{4-[2-(4-bromo-2-trifluoromethoxy-phenyl)-ethylamino]-cyclohexyl}-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride obtained in step B of example 37 (250 mg, 0.4 mmol) in EtOH (5 mL) was added 10% Pd/C (75 mg). The mixture was stirred at ambient temperature under hydrogen atmosphere for 17 hr, filtered, poured into saturated aqueous NaHCO3. The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (NH-silica gel, 50% EtOAc in hexane) to give a colorless oil. To a solution of above oil in EtOAc (4 mL) was added 4 M hydrogen chloride in EtOAc (0.25 mL). The mixture was stirred at ambient temperature for 1 hr and concentrated. The residue was suspended with Et2O (15 mL) and stirred at ambient tempareture for 1 hr. The solid was collected by filtration, washed with Et20, and dried under reduced pressure to give cis-N4,N4-dimethyl-N2-{4-[2-(2-trifluoromethoxy-phenyl)-ethylamino]-cyclohexyl}-quinazoline-2,4-diamine dihydrochloride (104 mg, 48%) as a white solid.

Aufarbeitung

  1. filtrationfiltered
  2. additionpoured into saturated aqueous NaHCO3
  3. extractionThe aqueous layer was extracted with CHCl3 (three times)
  4. dry with materialThe combined organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography (NH-silica gel, 50% EtOAc in hexane)
  8. customto give a colorless oil
  9. stirringThe mixture was stirred at ambient temperature for 1 hr
  10. concentrationconcentrated
  11. stirringstirred at ambient tempareture for 1 hr
  12. filtrationThe solid was collected by filtration
  13. washwashed with Et20
  14. customdried under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-427ad8c0503f4dd897582072924eb09f
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07544690B2

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