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Lithium Hydroxide → 6-tert-Butyl-2-{3-[5-(5-ethanesulfonyl-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one

HRID 449605
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 449605
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH2:28][CH3:29])(=[O:27])=[O:26])=[CH:21][N:20]=3)[C:15](=[O:30])[N:14]([CH3:31])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:32]1[N:41]=[CH:40][C:39]2[C:34](=[C:35]([F:46])[CH:36]=[C:37]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:38]=2)[C:33]1=[O:47])(=O)C.[Li+].[OH-]>O1CCOCC1>[C:42]([C:37]1[CH:38]=[C:39]2[C:34](=[C:35]([F:46])[CH:36]=1)[C:33](=[O:47])[N:32]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:24]=[CH:23][C:22]([S:25]([CH2:28][CH3:29])(=[O:26])=[O:27])=[CH:21][N:20]=4)[C:15](=[O:30])[N:14]([CH3:31])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:41]=[CH:40]2)([CH3:43])([CH3:44])[CH3:45]
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Komponenten

4

Edukt 2

HCID 3939Lithium HydroxideHCID 667427742-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(ethylsulfonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Produkt 1

HCID 566556686-tert-Butyl-2-{3-[5-(5-ethanesulfonyl-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-oneAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31275
1,4-Dioxane
Lösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

In a 250 mL round-bottomed flask, 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(ethylsulfonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (159 mg, 241 μmol) was combined with dioxane (5 ml) and 1M LiOH (1 ml) to give a brown solution. The reaction mixture was stirred at 25° C. for 18 h. The crude reaction mixture was concentrated in vacuo. The residue was partitioned between water and DCM. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 4% MeOH in DCM) to afford 0.039 g (54%) of the title compound as a tan solid. (M−H)+=617 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ: 8.85 (d, J=2.3 Hz, 1H), 8.79 (s, 1H), 8.63 (s, 1H), 8.30 (d, J=2.3 Hz, 1H), 8.06 (dd, J=8.7, 2.3 Hz, 1H), 7.43-7.73 (m, 5H), 7.07 (d, J=8.7 Hz, 1H), 4.45 (s, 2H), 3.94 (s, 3H), 3.15 (d, J=7.2 Hz, 2H), 1.44 (s, 9H), 1.33 (t, J=7.2 Hz, 3H).

Aufarbeitung

  1. customto give a brown solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. customThe residue was partitioned between water and DCM
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 24 g, 0% to 4% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-d7c18a29477c4f6cad3eb6dde19de08d
Quelldatensatz
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08481540B2

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