18-Crown-6 → 1-{4-[3-(Difluoromethyl)-2-oxoimidazolidin-1-yl]-2-fluorophenyl}-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1624826Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1624826
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][NH:10][C:9]2=[O:13])[CH:5]=[CH:4][C:3]=1[N:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17](=[O:22])[C:16]([C:23]2[N:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:26]=[CH:25][CH:24]=2)=[N:15]1.Cl[C:35]([F:40])([F:39])C([O-])=O.[Na+].C1OCCOCCOCCOCCOCCOC1>C(#N)C>[F:39][CH:35]([F:40])[N:10]1[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][C:3]([N:14]3[CH:19]=[C:18]([O:20][CH3:21])[C:17](=[O:22])[C:16]([C:23]4[N:27]([C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=5)[N:26]=[CH:25][CH:24]=4)=[N:15]3)=[C:2]([F:1])[CH:7]=2)[C:9]1=[O:13]

Komponenten

5

Edukt 3

HCID 2855718-Crown-6HCID 2734985Sodium chlorodifluoroacetateHCID 580724131-[2-Fluoro-4-(2-oxoimidazolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Produkt 1

HCID 580725261-{4-[3-(Difluoromethyl)-2-oxoimidazolidin-1-yl]-2-fluorophenyl}-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneAusbeute 2,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 1-[2-fluoro-4-(2-oxoimidazolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (100 mg, 0.22 mmol), sodium chlorodifluoroacetate (40 mg, 0.26 mmol), and 18-crown-6 (12 mg, 0.044 mmol) in acetonitrile (10 mL) was stirred at 90° C. for 20 h. After cooling to room temperature, to the reaction mixture was added silica gel. This mixture was evaporated, and purified by silica gel column chromatography eluting with AcOEt/MeOH (1/0 to 10/1) to give the title compound (2.5 mg, 2.3% yield) as a pale yellow powder: 1H NMR (300 MHz, DMSO-d6): δ ppm 1.11-1.40 (4H, m), 3.61-3.86 (4H, m), 6.96 (1H, d, J=1.9 Hz), 7.01-7.15 (1H, m), 7.16-7.50 (6H, m), 7.71 (1H, dd, J=13.6, 2.3 Hz), 7.79 (1H, d, J=2.3 Hz), 8.47 (1H, d, J=1.9 Hz). LC-MS (ESI) m/z 497 [M+H]+.

Aufarbeitung

  1. temperatureAfter cooling to room temperature, to the reaction mixture
  2. additionwas added silica gel
  3. customThis mixture was evaporated
  4. custompurified by silica gel column chromatography
  5. washeluting with AcOEt/MeOH (1/0 to 10/1)

Quellen und Nachweise

ORD-Eintrag
ord-17aabec5c0f14630b45f59f7d04a5db4
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778944B2

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