Acetyl chloride → 6-(1-Acetylpiperidin-3-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline

HRID 1948919Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1948919
[C:1](Cl)(=[O:3])[CH3:2].[Cl:5][C:6]1[C:7]([F:32])=[C:8]([CH:29]=[CH:30][CH:31]=1)[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:27][CH3:28])=[C:17]([O:20][CH:21]3[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]3)[CH:18]=2)[N:13]=[CH:12][N:11]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([N:23]1[CH2:24][CH2:25][CH2:26][CH:21]([O:20][C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][C:16]=2[O:27][CH3:28])[N:13]=[CH:12][N:11]=[C:10]3[NH:9][C:8]2[CH:29]=[CH:30][CH:31]=[C:6]([Cl:5])[C:7]=2[F:32])[CH2:22]1)(=[O:3])[CH3:2]

Komponenten

5

Edukt 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 104537624-(3-Chloro-2-fluoroanilino)-6-(piperidin-3-yloxy)-7-methoxyquinazoline

Produkt 1

HCID 104336166-(1-Acetylpiperidin-3-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolineAusbeute 47,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Acetyl chloride (27 mg) was added to a solution of 4-(3-chloro-2-fluoroanilino)-6-(piperidin-3-yloxy)-7-methoxyquinazoline (starting material described in Example 22; 134 mg) and diisopropylethylamine (65 mg) in methylene chloride (5 ml) and the reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was adsorbed onto silica and purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5). The fractions containing the required product were combined and evaporated to give the title product (0.07 g); 1H NMR Spectrum: (DMSO d6 at 373K) 1.52-1.62 (m, 1H), 1.80-1.94 (m, 2H), 2.00 (s, 3H), 2.06-2.15 (m, 1H), 3.43-3.64 (m, 3H), 3.82-4.04 (m, 4H), 4.58 (m, 1H), 7.20-7.29 (m, 2H), 7.42 (t, 1H), 7.59 (t, 1H), 7.93 (s, 1H), 8.40 (s, 1H), 9.30 (s, 1H); Mass Spectrum: (M+H)+ 445.

Aufarbeitung

  1. custompurified by column chromatography
  2. washeluting
  3. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5)
  4. additionThe fractions containing the required product
  5. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-f7883addf33743ef88f7075bc0adc9cb
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399667B2

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