p-Toluenesulfonic acid → 2-(4-((3R,5S)-4-Isopropyl-3,5-dimethylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591659Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 591659
[CH:1]([N:4]1[CH:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=2)[CH2:6][CH:5]1[CH3:19])([CH3:3])[CH3:2].OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1.[NH2:36][C:37]1[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[C:42]([O:48][CH3:49])[C:38]=1[C:39]([NH2:41])=[O:40]>CC(N(C)C)=O.O>[CH:1]([N:4]1[C@@H:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:18]=[CH:17][C:14]([C:15]3[NH:41][C:39](=[O:40])[C:38]4[C:37](=[CH:45][C:44]([O:46][CH3:47])=[CH:43][C:42]=4[O:48][CH3:49])[N:36]=3)=[CH:13][CH:12]=2)[CH2:6][C@H:5]1[CH3:19])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 866620244-(4-Isopropyl-3,5-dimethylpiperazin-1-yl)benzaldehyde

Produkt 1

HCID 1362626562-(4-((3R,5S)-4-Isopropyl-3,5-dimethylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-oneAusbeute 17,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of 4-(4-isopropyl-3,5-dimethylpiperazin-1-yl)benzaldehyde (0.400 g, 1.50 mmol), NaHSO3 (0.195 g, 1.80 mmol), and p-TsOH (0.030 g, 0.15 mmol) was added to a solution of 2-amino-4,6-dimethoxybenzamide (0.400 g, 2.40 mmol) in DMA (10 mL). The reaction was stirred at 140° C. for 4 hours, then at room temperature overnight. The mixture was diluted with H2O and extracted with CH2Cl2. The organics were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 1% to 10% MeOH/CH2Cl2, followed by reverse-phase chromatography, eluting with 10% to 90% CH3CN in H2O, afforded the title compound (0.114 g, 17%). 1H NMR (300 MHz, DMSO-d6): δ 11.68 (s, 1H), 8.09 (d, J=8.9 Hz, 2H), 6.78 (d, J=9.0 Hz, 2H), 6.66 (s, 1H), 6.44 (s, 1H), 3.87 (s, 3H), 3.83 (s, 3H), 3.41-3.44 (m, 2H), 3.11-3.23 (m, 5H), 1.00-1.03 (m, 12H). ESI MS m/z 437 [M+H]+.

Aufarbeitung

  1. customat room temperature
  2. customovernight
  3. extractionextracted with CH2Cl2
  4. washThe organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography on silica gel
  9. washeluting with 1% to 10% MeOH/CH2Cl2
  10. washeluting with 10% to 90% CH3CN in H2O

Quellen und Nachweise

ORD-Eintrag
ord-826f31a2a8a3474e92a2a1941ba96671
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238640B2

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