3-(4-Methyl-1-piperazine)propan-1-ol → 5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4(3H)-one

HRID 749182

Reaktionsgleichung

Reaktionsgleichung von HRID 749182
[C:1]([O:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:24]=[C:23](F)[CH:22]=[C:21]3[C:16]=2[C:17](=[O:26])[NH:18][CH:19]=[N:20]3)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][OH:37])[CH2:30][CH2:29]1.CC(C)([O-])C.[K+]>COCCOCCOC.ClCCl.O>[NH3:8].[C:1]([O:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:24]=[C:23]([O:37][CH2:36][CH2:35][CH2:34][N:31]3[CH2:30][CH2:29][N:28]([CH3:27])[CH2:33][CH2:32]3)[CH:22]=[C:21]3[C:16]=2[C:17](=[O:26])[NH:18][CH:19]=[N:20]3)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 3

HCID 792083-(4-Methyl-1-piperazine)propan-1-olHCID 23665647Potassium tert-butoxideHCID 1363519525-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-fluoroquinazolin-4(3H)-one

Produkt 2

HCID 222AmmoniaHCID 1363519515-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4(3H)-oneAusbeute 109,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8150DiglymeLösungsmittel

Versuchsvorschrift

5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-fluoroquinazolin-4(3H)-one (5.45 mg, 1.5 mmol) in anhydrous diglyme (15 ml) was reacted with 3-(4-methylpiperazin-1-yl)propan-1-ol (474 mg, 3 mmol) in the presence of potassium tert-butoxide (11.77 g, 10 mmol) at 100° C. for 4 hours. The reaction mixture was diluted with dichloromethane (10 ml) and water (10 ml) and the pH adjusted to 7.7. The mixture was extracted several times with dichloromethane and the organic phase dried (magnesium sulphate), evaporated and the residue purified by chromatography on silica gel. Elution with dichloromethane:methanolic ammonia (9:1) yielded 5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4(3H)-one (411 mg, 55% yield):

Aufarbeitung

  1. extractionThe mixture was extracted several times with dichloromethane
  2. dry with materialthe organic phase dried (magnesium sulphate)
  3. customevaporated
  4. customthe residue purified by chromatography on silica gel
  5. washElution with dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-dbb39fb66c83498ea7f50391fc9ea242
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07402585B2

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