Potassium Carbonate → (5S)-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)-7-(1-methyl-2-oxopyrrolidin-5-ylmethoxy)quinazoline

HRID 454315Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 454315
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC(S([CH2:40][C@H:41]2[N:45]([CH3:46])[C:44](=[O:47])[CH2:43][CH2:42]2)(=O)=O)=CC=1>CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:40][C@H:41]1[N:45]([CH3:46])[C:44](=[O:47])[CH2:43][CH2:42]1)[N:9]=[CH:8][N:7]=[C:6]2[O:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 57001804(5S)-5-(p-toluenesulphonylmethyl)-1-methyl-2-pyrrolidinoneHCID 1357631087-hydroxy-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)quinazoline

Produkt 1

HCID 57281674(5S)-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)-7-(1-methyl-2-oxopyrrolidin-5-ylmethoxy)quinazolineAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a solution of 7-hydroxy-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)quinazoline (225 mg, 0.7 mmol), (prepared as described in Example 49), in DMF was added powdered potassium carbonate (290 mg, 2.1 mmol) and (5S)-5-(p-toluenesulphonylmethyl)-1-methyl-2-pyrrolidinone (340 mg, 1.2 mmol). The reaction was then heated at 95° C. for 5 hours. The inorganic material was filtered off and the DMF removed by evaporation. The residue was then purified by chromatography eluting from methylene chloride to 12% methanol/88% methylene chloride (+1% ammonium hydroxide). The product was evaporated, triturated with ether and filtered to give (5S)-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)-7-(1-methyl-2-oxopyrrolidin-5-ylmethoxy)quinazoline (100 mg, 33%) as a white solid.

Aufarbeitung

  1. filtrationThe inorganic material was filtered off
  2. customthe DMF removed by evaporation
  3. customThe residue was then purified by chromatography
  4. washeluting from methylene chloride to 12% methanol/88% methylene chloride (+1% ammonium hydroxide)
  5. customThe product was evaporated
  6. customtriturated with ether
  7. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-38a66723fb84480186985e15b40c255c
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08492560B2

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