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Cesium carbonate → (2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(4-methyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl acetate

HRID 1185201
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1185201
[CH3:1][CH:2]1[C:7]2=[CH:8][C:9]([NH2:11])=[N:10][N:6]2[CH2:5][CH2:4][O:3]1.[C:12]([O:15][CH2:16][C:17]1[C:18]([N:32]2[N:41]=[CH:40][C:39]3[C:34](=[C:35]([F:46])[CH:36]=[C:37]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:38]=3)[C:33]2=[O:47])=[N:19][CH:20]=[CH:21][C:22]=1[C:23]1[CH:28]=[C:27](Br)[C:26](=[O:30])[N:25]([CH3:31])[CH:24]=1)(=[O:14])[CH3:13].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[C:12]([O:15][CH2:16][C:17]1[C:18]([N:32]2[N:41]=[CH:40][C:39]3[C:34](=[C:35]([F:46])[CH:36]=[C:37]([C:42]([CH3:44])([CH3:43])[CH3:45])[CH:38]=3)[C:33]2=[O:47])=[N:19][CH:20]=[CH:21][C:22]=1[C:23]1[CH:28]=[C:27]([NH:11][C:9]2[CH:8]=[C:7]3[CH:2]([CH3:1])[O:3][CH2:4][CH2:5][N:6]3[N:10]=2)[C:26](=[O:30])[N:25]([CH3:31])[CH:24]=1)(=[O:14])[CH3:13]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86684026(4-(5-Bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-3-yl)methyl acetateHCID 866840524-Methyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-amine

Produkt 1

HCID 86684051
(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(4-methyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl acetate
Ausbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 150h (25 mg, 1.0 eq., 0.16 mmol), (4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-3-yl)methyl acetate 142c (181 mg, 2.0 eq., 0.32 mmol), Pd2(dba)3 (15 mg, 0.1 eq., 0.016 mmol), Xantphos (19 mg, 0.2 eq., 0.032 mmol), Cs2CO3 (105 mg, 2.0 eq., 0.32 mmol), and dioxane (10 mL). The mixture was subjected to three cycles of vacuum/argon flush and stirred at 100° C. for 2 hr. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 150i as a brown solid (48 mg, 48%).

Aufarbeitung

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customflush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 20:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-30484606691b4bed871a19b6981c64e6
Quelldatensatz
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08669251B2

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