Potassium Carbonate → acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{2-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridin-4-yl}-benzyl ester

HRID 402937Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 402937
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:10]=2)[CH:3]=1.[C:23]([C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([F:37])[CH:36]=1)[C:33](=[O:38])[N:32]([C:39]1[CH:49]=[CH:48][CH:47]=[C:46](B3OC(C)(C)C(C)(C)O3)[C:40]=1[CH2:41][O:42][C:43](=[O:45])[CH3:44])[N:31]=[CH:30]2)([CH3:26])([CH3:25])[CH3:24].C([O-])([O-])=O.[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:23]([C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([F:37])[CH:36]=1)[C:33](=[O:38])[N:32]([C:39]1[CH:49]=[CH:48][CH:47]=[C:46]([C:2]3[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]4[CH:10]=[CH:11][C:12]([C:15]([N:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)=[O:16])=[CH:13][N:14]=4)[CH:3]=3)[C:40]=1[CH2:41][O:42][C:43](=[O:45])[CH3:44])[N:31]=[CH:30]2)([CH3:24])([CH3:25])[CH3:26]

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 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 86686837[6-(4-Bromo-pyridin-2-ylamino)-pyridin-3-yl]-morpholin-4-yl-methanone

Produkt 1

HCID 86686836acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{2-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridin-4-yl}-benzyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Versuchsvorschrift

[6-(4-Bromo-pyridin-2-ylamino)-pyridin-3-yl]-morpholin-4-yl-methanone (200 mg, 0.55 mmol), acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-benzyl ester (410 mg, 0.83 mmol) and K2CO3(152 mg, 1.10 mmol) were dissolved in dioxane/H2O (10:1, 11 ml). Under N2 atmosphere, Pd2(dba)3 (50 mg, 0.055 mmol) and X-phos (105 mg, 0.22 mmol) was added and the mixture was stirred at reflux temperature overnight. After the completion of the reaction, the mixture was cooled to room temperature and filtered. The organic layer was washed with saturated brine, dried over sodium sulfate and concentrated. The residue was purified by silica gel column (petroleum ether:ethyl acetate=2:1). The desired product was obtained as a yellow solid (200 mg, yield 56%). LC-MS: 651[M+1]+, tR=1.397 min.

Aufarbeitung

  1. temperatureat reflux temperature overnight
  2. customAfter the completion of the reaction
  3. filtrationfiltered
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column (petroleum ether:ethyl acetate=2:1)

Quellen und Nachweise

ORD-Eintrag
ord-a1ef462ef80443c2953a867ed11cc4fb
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08742098B2

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