1,1,3,3-Tetramethylguanidine → 5,7-dimethoxy-2-(6-(4-(2-methoxyethyl)piperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one

HRID 922360Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 922360
F[C:2]1[N:7]=[C:6]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([O:21][CH3:22])=[CH:13][C:14]=3[O:19][CH3:20])[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[CH3:23][O:24][CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.CN(C)C(N(C)C)=N>CS(C)=O.C(OCC)(=O)C>[CH3:20][O:19][C:14]1[CH:13]=[C:12]([O:21][CH3:22])[CH:11]=[C:10]2[C:15]=1[C:16](=[O:18])[NH:17][C:8]([C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([N:30]3[CH2:31][CH2:32][N:27]([CH2:26][CH2:25][O:24][CH3:23])[CH2:28][CH2:29]3)[N:7]=1)=[N:9]2

Komponenten

6

Edukt 3

HCID 664601,1,3,3-TetramethylguanidineHCID 27346381-(2-Methoxyethyl)piperazineHCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

Produkt 1

HCID 1362488325,7-dimethoxy-2-(6-(4-(2-methoxyethyl)piperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-oneAusbeute 49,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.100 g, 0.33 mmol), 1-(2-methoxyethyl)piperazine (0.072 g, 0.49 mmol) and 1,1,3,3-tetramethylguanidine (0.096 g, 0.83 mmol) in dry DMSO (2 mL) was heated at 80° C. for 17 h. After that time the reaction mixture was cooled to rt and diluted with ethyl acetate (30 mL). The organic phase was washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 97:3 dichloromethane/methanol to 95:5 dichloromethane/methanol) to give 5,7-dimethoxy-2-(6-(4-(2-methoxyethyl)piperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one (0.070 g, 49%) as a yellow solid: mp 99-101° C.; 1H NMR (400 MHz, CDCl3) δ 10.32 (s, 1H), 7.85 (d, J=7.42 Hz, 1H), 7.61-7.71 (m, 1H), 6.77-6.87 (m, 2H), 6.48 (d, J=1.95 Hz, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.64-3.71 (m, 4H), 3.59 (t, J=5.47 Hz, 2H), 3.40 (s, 3H), 2.61-2.71 (m, 6H); ESI MS m/z 426 [M+H]+.

Aufarbeitung

  1. temperatureAfter that time the reaction mixture was cooled to rt
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe product was purified by flash column chromatography (silica gel, 97:3 dichloromethane/methanol to 95:5 dichloromethane/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-62edb79b42134b2383f5114526354937
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09278940B2

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