Potassium Carbonate → 6-tert-butyl-2-{3-[5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one

HRID 1431120Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1431120
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:23]=[C:22]([CH3:24])[N:21]([CH3:25])[N:20]=3)[C:15](=[O:26])[N:14]([CH3:27])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:28]1[N:37]=[CH:36][C:35]2[C:30](=[C:31]([F:42])[CH:32]=[C:33]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:34]=2)[C:29]1=[O:43])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[C:38]([C:33]1[CH:34]=[C:35]2[C:30](=[C:31]([F:42])[CH:32]=1)[C:29](=[O:43])[N:28]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:23]=[C:22]([CH3:24])[N:21]([CH3:25])[N:20]=4)[C:15](=[O:26])[N:14]([CH3:27])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:37]=[CH:36]2)([CH3:41])([CH3:39])[CH3:40]

Komponenten

4

Edukt 2

HCID 11430Potassium CarbonateHCID 667431562-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Produkt 1

HCID 566558106-tert-butyl-2-{3-[5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-oneAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (186 mg, 318 μmol, Eq: 1.00) in MeOH (15.0 ml) was added potassium carbonate (87.8 mg, 635 μmol, Eq: 2.0). The reaction mixture stirred at 40° C. for 2 h. The solution was cooled to room temperature. Concentrated in vacuo. The residue was taken up in DCM/water. The layers were separated. The aqueous layer was extracted once with DCM. The organic layers were combined, and then dried over Na2SO4. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 35% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give 6-tert-butyl-2-{3-[5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one (75 mg, 44%). LC/MS-ESI observed [M+H]+ 544. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.43 (s, 9H) 2.28 (s, 3H) 3.75 (s, 3H) 3.88 (s, 3H) 4.40 (s, 2H) 5.92 (s, 1H) 7.41-7.60 (m, 4H) 7.62-7.69 (m, 1H) 7.78 (s, 1H) 7.96 (s, 1H) 8.29 (d, J=2.64 Hz, 1H)

Aufarbeitung

  1. temperatureThe solution was cooled to room temperature
  2. concentrationConcentrated in vacuo
  3. customThe layers were separated
  4. extractionThe aqueous layer was extracted once with DCM
  5. dry with materialdried over Na2SO4
  6. concentrationConcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 12 g, 0% to 35% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)

Quellen und Nachweise

ORD-Eintrag
ord-17ffc6f0f7c645b89db069fc30afa19c
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940741B2

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