Triethylamine → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochloride

HRID 1420984Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1420984
[C:1]([Cl:9])(=[O:8])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.O.Cl.[Cl:12][C:13]1[CH:36]=[CH:35][C:16]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][NH:33][CH3:34])=[C:25]([O:28][CH3:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)=[C:15]([F:37])[CH:14]=1.C(N(CC)CC)C>C(Cl)Cl>[ClH:9].[Cl:12][C:13]1[CH:36]=[CH:35][C:16]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][N:33]([CH3:34])[C:1]([C:2]4[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=4)=[O:8])=[C:25]([O:28][CH3:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)=[C:15]([F:37])[CH:14]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 417436Pyridine-4-carbonyl chlorideHCID 226249694-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(methylamino)ethoxy)quinazoline hydrochloride hydrate

Produkt 1

HCID 226250114-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochlorideAusbeute 144,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Isonicotinoyl chloride (36 mg, 0.2 mmol) was added to a suspension of 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(methylamino)ethoxy)quinazoline hydrochloride hydrate (90 mg, 0.1 mmol), (prepared as described for the starting material in Example 54), in methylene chloride (3 ml) and triethylamine (80 mg, 0.8 mmol) was then added dropwise. The mixture was stirred for 30 minutes at ambient temperature and the solvent was then removed by evaporation. The residue was partitioned between ethyl acetate and water, the organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The suspension was diluted with ether, the precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochloride (75 mg, 67%).

Aufarbeitung

  1. custom(prepared
  2. customthe solvent was then removed by evaporation
  3. customThe residue was partitioned between ethyl acetate and water
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. dissolutionThe residue was dissolved in methylene chloride/methanol
  9. addition3M ethereal hydrogen chloride (0.5 ml) was added
  10. additionThe suspension was diluted with ether
  11. filtrationthe precipitate was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-091a59758a114721a20ab1e299d89c6c
Quelldatensatz
uspto-grants-2000_06
Patentnummer
US06071921

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