Diethyl Ether → 7-(3-Benzyloxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride

HRID 1596254

Reaktionsgleichung

Reaktionsgleichung von HRID 1596254
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25](O)=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.CCOCC>C(Cl)Cl>[ClH:13].[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:25]1[CH:24]=[C:23]2[C:28]([C:19]([NH:18][C:17]3[CH:32]=[CH:33][C:14]([Cl:13])=[CH:15][C:16]=3[F:34])=[N:20][CH:21]=[N:22]2)=[CH:27][C:26]=1[O:29][CH3:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 3283Diethyl EtherHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 3479713-Benzyloxy-1-propanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Produkt 1

HCID 226248927-(3-Benzyloxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochlorideAusbeute 56,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
5 °C

Versuchsvorschrift

A solution of 3-benzyloxy-1-propanol (150 μl, 0.9 mmol) was added to tributyephosphine (376 mg, 1.9 mmol) and 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.63 mmol), (prepared as described for the starting material in Example 4), in methylene chloride (20 ml) at 5° C. To the resulting mixture 1,1′-azodicarbonyldipiperidine (480 mg, 1.9 mmol) was added, the mixture stirred at 5° C. for 1 hour, allowed to warm to ambient temperature and stirred overnight. Ether (10 ml) was added, the mixture stirred for 15 minutes and the precipitated solids removed by filtration. The volatiles were removed from the filtrate by evaporation, and the residue was partitioned between ethyl acetate and water. The organic layer was separated, dried (MgSO4) and the solvent removed by evaporation. The residue was dissolved in acetone, and hydrogen chloride in ether (0.6 ml of a 1M solution, 0.6 mmol) added. The resulting precipitated product was collected by filtration and dried to give 7-(3-benzyloxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (90 mg, 31%).

Aufarbeitung

  1. custom(prepared
  2. customat 5° C
  3. temperatureto warm to ambient temperature
  4. stirringstirred overnight
  5. stirringthe mixture stirred for 15 minutes
  6. customthe precipitated solids removed by filtration
  7. customThe volatiles were removed from the filtrate by evaporation
  8. customthe residue was partitioned between ethyl acetate and water
  9. customThe organic layer was separated
  10. dry with materialdried (MgSO4)
  11. customthe solvent removed by evaporation
  12. dissolutionThe residue was dissolved in acetone
  13. additionhydrogen chloride in ether (0.6 ml of a 1M solution, 0.6 mmol) added
  14. customThe resulting precipitated product
  15. filtrationwas collected by filtration
  16. customdried

Quellen und Nachweise

ORD-Eintrag
ord-29e009b088854843a97651fcc0c3c323
Quelldatensatz
uspto-grants-2001_09
Patentnummer
US06291455B1

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