Morpholine → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(3-morpholinocarbonylpropoxy)quinazoline

HRID 547198Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 547198
Cl.CN(C)CCCN=C=NCC.[C:13]([CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:29]=[C:28]2[C:23]([C:24]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=3[F:38])=[N:25][CH:26]=[N:27]2)=[CH:22][C:21]=1[O:39][CH3:40])(O)=[O:14].[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>CN(C)C1C=CN=CC=1.CN(C=O)C>[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([NH:30][C:24]2[C:23]3[C:28](=[CH:29][C:20]([O:19][CH2:18][CH2:17][CH2:16][C:13]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)=[O:14])=[C:21]([O:39][CH3:40])[CH:22]=3)[N:27]=[CH:26][N:25]=2)=[C:32]([F:38])[CH:33]=1

Komponenten

6

Edukt 3

HCID 8083MorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 224782937-(3-Carboxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline

Produkt 1

HCID 187534834-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(3-morpholinocarbonylpropoxy)quinazolineAusbeute 46,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (94 mg, 4.9 mmol) was added to a mixture of 7-(3carboxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (164 mg, 0.4 mmol), morpholine (0.11 g; 1.26 mmol) and 4-dimethylaminopyridine (200 mg, 1.64 mmol) in DMF (5 ml). The reaction mixture was stirred at ambient temperature for 24 hours and the volatiles were removed by evaporation. Water was added to the residue and the aqueous mixture was extracted with methylene chloride (3×30 ml). The extracts were combined and the solvent removed by evaporation. The residue was triturated with ether and the precipitate was collected by filtration. The solid was purified by column chromatography eluting with methylene chloride/methanol/aqueous ammonia (100/8/1). The purified product was triturated with acetone, collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-morpholinocarbonylpropoxy)quinazoline (88 mg, 46%).

Aufarbeitung

  1. customthe volatiles were removed by evaporation
  2. additionWater was added to the residue
  3. extractionthe aqueous mixture was extracted with methylene chloride (3×30 ml)
  4. customthe solvent removed by evaporation
  5. customThe residue was triturated with ether
  6. filtrationthe precipitate was collected by filtration
  7. customThe solid was purified by column chromatography
  8. washeluting with methylene chloride/methanol/aqueous ammonia (100/8/1)
  9. customThe purified product was triturated with acetone
  10. filtrationcollected by filtration
  11. customdried

Quellen und Nachweise

ORD-Eintrag
ord-48d581c8cd7d4110af7a88ac446811e5
Quelldatensatz
uspto-grants-2011_05
Patentnummer
USRE042353E1

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