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Dimethylformamide → 3-(4,4'-Dimethoxybenzhydryl)-6-(N-methyl-N-isobutyrylcarbamoyl)-amino-2-propyl-quinazolin-4(3H)-one

HRID 1770146
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1770146
[H-].[Na+].N[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([CH2:14][CH2:15][CH3:16])[N:8]([CH:17]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[C:7]2=[O:34].[CH2:35]([O:39]C(Cl)=O)[CH:36]([CH3:38])[CH3:37].C[Si](C)(C)[N-:45][Si](C)(C)C.[Li+].IC.[CH3:55][N:56]([CH:58]=[O:59])C>C1COCC1.CCOC(C)=O>[CH3:33][O:32][C:29]1[CH:28]=[CH:27][C:26]([CH:17]([N:8]2[C:7](=[O:34])[C:6]3[C:11](=[CH:12][CH:13]=[C:4]([C:58](=[O:59])[N:56]([CH3:55])[C:35](=[O:39])[CH:36]([CH3:37])[CH3:38])[C:5]=3[NH2:45])[N:10]=[C:9]2[CH2:14][CH2:15][CH3:16])[C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:31][CH:30]=1
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Komponenten

9

Edukt 6

HCID 6228Dimethylformamide2×HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 62365Isobutyl chloroformateHCID 2733832Lithium hexamethyldisilazaneHCID 19934842HCID 19934842, Verbindung

Produkt 1

HCID 67789925
3-(4,4'-Dimethoxybenzhydryl)-6-(N-methyl-N-isobutyrylcarbamoyl)-amino-2-propyl-quinazolin-4(3H)-one
Ausbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a suspension of 81.5 mg (2.7 mmol) of 80% NaH in 3 ml of dry DMF at 0° C. under nitrogen was added dropwise a solution of 1.03 g (2.5 mmol) of 6-amino-3-(4,4'-dimethoxybenzhydryl)-2-propyl-quinazolin-4(3H)-one dissolved in 3 ml of DMF. The resulting mixture was stirred for 30 minutes and was then treated with 0.35 ml (2.7 mmol) of isobutylchloroformate neat. The solution was stirred for 30 minutes and then treated with 2.97 ml (2.97 mmol) of a 1M solution of lithium hexamethyldisilazide in THF. The dark solution was stirred for a further 30 minutes at 0° C. and then was treated with 0.2 ml (3.26 mmol) of iodomethane neat. The mixture was stirred overnight at room temperature, poured into 50 ml of EtOAc and washed consecutively with water (2×10 ml), brine (1×10 ml) and dried over MgSO4 . The product was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexanes to give 0.9 g (1.7 mmol) of an oil. 71% yield. 1H-NMR (CDCl3): 0.82-0.91 (m, 6H), 0.96 (d, 3H, J=6.8 Hz), 1.52 (m, 2H), 1.88 (m, 1H), 2.67 (bt, 2H), 3.35 (s, 3H), 3.80 (s, 6H), 3.90 (d, 2H, J=6.6 Hz), 6.87 (d, 4H, J=8.8 Hz), 7.20 (d, 4H, J=8.8 Hz), 7.61 (m, 1H), 7.78 (m, 1H), 8.01 (d, 1H, 2 Hz).

Aufarbeitung

  1. stirringThe solution was stirred for 30 minutes
  2. stirringThe dark solution was stirred for a further 30 minutes at 0° C.
  3. stirringThe mixture was stirred overnight at room temperature
  4. washwashed consecutively with water (2×10 ml), brine (1×10 ml)
  5. dry with materialdried over MgSO4
  6. customThe product was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-353f06e924294ef19b2f9c8a8c555194
Quelldatensatz
uspto-grants-1995_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US05385894

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