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Potassium Phosphate, Tribasic → 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

HRID 1431103
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1431103
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:23]([CH3:25])[CH3:24])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:26]([O:29][CH2:30][C:31]1[C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][CH:34]=[CH:33][C:32]=1[N:46]1[N:55]=[CH:54][C:53]2[C:48](=[C:49]([F:60])[CH:50]=[C:51]([C:56]([CH3:59])([CH3:58])[CH3:57])[CH:52]=2)[C:47]1=[O:61])(=[O:28])[CH3:27].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:26]([O:29][CH2:30][C:31]1[C:36]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([CH:23]([CH3:25])[CH3:24])[CH2:19][CH2:18]4)=[CH:13][N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=2)=[CH:35][CH:34]=[CH:33][C:32]=1[N:46]1[N:55]=[CH:54][C:53]2[C:48](=[C:49]([F:60])[CH:50]=[C:51]([C:56]([CH3:58])([CH3:57])[CH3:59])[CH:52]=2)[C:47]1=[O:61])(=[O:28])[CH3:27]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 594737692-(6-(tert-Butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 667422216-chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

Produkt 1

HCID 66743191
2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate
Ausbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

6-Chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (123 mg, 340 μmol, Eq: 1.2), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (140 mg, 283 μmol, Eq: 1.00), potassium phosphate tribasic (180 mg, 850 μmol, Eq: 3.00) and X-PHOS (13.5 mg, 28.3 μmol, Eq: 0.10) were dissolved in dioxane (10 ml) and water (1.0 mL). The reaction was degassed with Ar. Pd2(dba)3 (13.0 mg, 14.2 μmol, Eq: 0.05) was added and the reaction was heated to 125° C. for 30 min in the microwave. The solution was dried over MgSO4 and filtered. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 5% MeOH/DCM gradient) to give 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (153 mg, 78%). LC/MS-ESI observed [M+H]+ 695.

Aufarbeitung

  1. customThe reaction was degassed with Ar
  2. dry with materialThe solution was dried over MgSO4
  3. filtrationfiltered
  4. concentrationConcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 12 g, 0% to 5% MeOH/DCM gradient)

Quellen und Nachweise

ORD-Eintrag
ord-1f43d5ec6cae498ba5df11def1f70776
Quelldatensatz
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08940741B2

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