Triphenylphosphine → 7-(1-(Tert-butoxycarbonyl)piperidin-4-ylmethoxy)-4-(2-fluoro-4-methylanilino)-6-methoxyquinazoline

HRID 238111Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 238111
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:20][C:21]1[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:22]=1[NH:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1.[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][CH:52]([CH2:55]O)[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:44])[CH3:43].N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][CH:52]([CH2:55][O:36][C:30]2[CH:29]=[C:28]3[C:33]([C:24]([NH:23][C:22]4[CH:37]=[CH:38][C:39]([CH3:41])=[CH:40][C:21]=4[F:20])=[N:25][CH:26]=[N:27]3)=[CH:32][C:31]=2[O:34][CH3:35])[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:43])[CH3:44]

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 135537648HCID 135537648, Verbindung

Produkt 1

HCID 109620857-(1-(Tert-butoxycarbonyl)piperidin-4-ylmethoxy)-4-(2-fluoro-4-methylanilino)-6-methoxyquinazolineAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Triphenylphosphine (2.19 g, 8.36 mmol) was added to a suspension of 4-(2-fluoro-4-methylanilino)-7-hydroxy-6-methoxyquinazoline (1 g, 3.34 mmol) in methylene chloride (10 ml) cooled at 0° C., followed by 1-(tert-butoxycarbonyl)-4-hydroxymethylpiperidine (1.08 g, 5.01 mmol), (prepared as described for the starting material in Example 1), and diethyl azodicarboxylate (1.31 ml, 8.36 mmol). After stirring for 2 hours at ambient temperature, the volatiles were removed under vacuum. The residue was purified by column chromatography eluting with methylene chloride/methanol (2/98). After removal of the solvent by evaporation, the residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 7-(1-(tert-butoxycarbonyl)piperidin-4-ylmethoxy)-4-(2-fluoro-4-methylanilino)-6-methoxyquinazoline (327 mg, 20%).

Aufarbeitung

  1. custom(prepared
  2. customthe volatiles were removed under vacuum
  3. customThe residue was purified by column chromatography
  4. washeluting with methylene chloride/methanol (2/98)
  5. customAfter removal of the solvent
  6. customby evaporation
  7. customthe residue was triturated with ether
  8. filtrationcollected by filtration
  9. washwashed with ether
  10. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-8cedcc4e606b404f96cfed195f5b2807
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642608B2

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