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

HRID 577382Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 577382
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-0c6f2a42e1f94dd9958cd3dc989715e1
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040548B2

Notizen zur Reaktion

Wird geladen…