Triphenylphosphine → 6-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline

HRID 2068012Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2068012
N(C(OCC)=O)=NC(OCC)=O.[F:13][C:14]1[C:22]([O:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:35][CH3:36])=[C:31]([OH:34])[CH:32]=3)[N:27]=[CH:26][N:25]=2)=[CH:21][CH:20]=[C:19]2[C:15]=1[CH:16]=[C:17]([CH3:37])[NH:18]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:57]([N:60]1[CH2:65][CH2:64][N:63]([CH2:66][CH2:67][CH2:68]O)[CH2:62][CH2:61]1)(=[O:59])[CH3:58]>C(Cl)Cl>[C:57]([N:60]1[CH2:65][CH2:64][N:63]([CH2:66][CH2:67][CH2:68][O:34][C:31]2[CH:32]=[C:33]3[C:28](=[CH:29][C:30]=2[O:35][CH3:36])[N:27]=[CH:26][N:25]=[C:24]3[O:23][C:22]2[C:14]([F:13])=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][C:17]([CH3:37])=[CH:16]3)[CH2:62][CH2:61]1)(=[O:59])[CH3:58]

Komponenten

6

Edukt 4

HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 112677704-(4-Fluoro-2-methylindol-5-yloxy)-6-hydroxy-7-methoxyquinazolineHCID 114467711-(4-(3-Hydroxypropyl)piperazin-1-yl)ethan-1-one

Produkt 1

HCID 101745406-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazolineAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Diethyl azodicarboxylate (0.178 g, 1.02 mmol) was added to a solution of 4-(4-fluoro-2-methylindol-5-yloxy)-6-hydroxy-7-methoxyquinazoline (0.267 g, 0.787 mmol), triphenylphosphine (0.31 g, 1.18 mmol) and 3-(4-acetylpiperazin-1-yl)propan-1-ol (0.176 g, 0.945 mmol) in methylene chloride (10 nm). After stirring for 15 minutes at ambient temperature, further triphenylphosphine (0.062 mg, 0.236 mmol) and diethyl azodicarboxylate (0.041 mg, 0.3 mmol) were added. After stirring for 1 hour at ambient temperature, the mixture was poured onto a column of silica and eluted with increasingly polar mixtures of ethyl acetate and methylene chloride followed by methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The residue was triturated under diethyl ether and the solid was filtered, washed with ether and dried under vacuum to give 6-(3-(4-acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline 0.210 g, 60%).

Aufarbeitung

  1. stirringAfter stirring for 1 hour at ambient temperature
  2. additionthe mixture was poured onto a column of silica
  3. washeluted
  4. temperaturewith increasingly polar mixtures of ethyl acetate and methylene chloride
  5. additionThe fractions containing the expected product
  6. customevaporated
  7. customThe residue was triturated under diethyl ether
  8. filtrationthe solid was filtered
  9. washwashed with ether
  10. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-b80d09c077a240cfac3062bd8df4ab6c
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08293902B2

Notizen zur Reaktion

Wird geladen…