Formaldehyde → Vandetanib

HRID 238089

Reaktionsgleichung

Reaktionsgleichung von HRID 238089
C=O.[Br:3][C:4]1[CH:37]=[CH:36][C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH:23]4[CH2:28][CH2:27][N:26]([C:29](OC(C)(C)C)=O)[CH2:25][CH2:24]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:6]([F:38])[CH:5]=1>C(O)=O>[Br:3][C:4]1[CH:37]=[CH:36][C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH:23]4[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:6]([F:38])[CH:5]=1

Komponenten

4

Edukt 2

HCID 712FormaldehydeHCID 11049999tert-Butyl 4-(((4-((4-bromo-2-fluorophenyl)amino)-6-methoxyquinazolin-7-yl)oxy)methyl)piperidine-1-carboxylate

Produkt 1

HCID 3081361VandetanibAusbeute 88,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 284Formic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

37% Aqueous formaldehyde (3.5 ml, 42 mmol) was added to a solution of 4-(4-bromo-2-fluoroanilino)-7-(1-(tert-butoxycarbonyl)piperidin-4-ylmethoxy)-6-methoxyquinazoline (3.49 g, 6.22 mmol), (prepared as described for the starting material in Example 1), in formic acid (35 ml). After heating at 95° C. for 4 hours the volatiles were removed under vacuum. The residue was suspended in water and the mixture was adjusted to pH10.5 by slow addition of a solution of 2N sodium hydroxide. The suspension was extracted with ethyl acetate. The organic layer was washed with brine, dried MgSO4 and evaporated to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (2.61 g, 88%).

Aufarbeitung

  1. custom(prepared
  2. customwere removed under vacuum
  3. additionthe mixture was adjusted to pH10.5 by slow addition of a solution of 2N sodium hydroxide
  4. extractionThe suspension was extracted with ethyl acetate
  5. washThe organic layer was washed with brine, dried MgSO4
  6. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-b64a3f845a024b3baf1b329aa1ac6b92
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642608B2

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