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Potassium Phosphate, Tribasic → (2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methylisoxazol-3-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

HRID 1185121
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1185121
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[N:30]=[CH:29][C:28]3[C:23](=[C:24]([F:35])[CH:25]=[C:26]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:27]=3)[C:22]2=[O:36])=[N:8][CH:9]=[CH:10][C:11]=1B1OC(C)(C)C(C)(C)O1)(=[O:3])[CH3:2].Br[C:38]1[CH:39]=[C:40]([NH:46][C:47]2[CH:51]=[C:50]([CH3:52])[O:49][N:48]=2)[C:41](=[O:45])[N:42]([CH3:44])[CH:43]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[N:30]=[CH:29][C:28]3[C:23](=[C:24]([F:35])[CH:25]=[C:26]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:27]=3)[C:22]2=[O:36])=[N:8][CH:9]=[CH:10][C:11]=1[C:38]1[CH:39]=[C:40]([NH:46][C:47]2[CH:51]=[C:50]([CH3:52])[O:49][N:48]=2)[C:41](=[O:45])[N:42]([CH3:44])[CH:43]=1)(=[O:3])[CH3:2]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 592164565-Bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridin-2(1H)-oneHCID 86683972(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

Produkt 1

HCID 86683978
(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methylisoxazol-3-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate
Ausbeute 87,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterKatalysatorHCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 3-(acetoxymethyl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-4-ylboronic acid 116c (438 mg, 1.06 mmol), 129a (150 mg, 0.60 mmol), Pd(dppf)Cl2 (19 mg, 0.026 mmol), K3PO4 (224 mg, 1.06 mmol), sodium acetate (87 mg, 1.06 mmol), water (5 drops), and acetonitrile (10 mL). After three cycles of vacuum/argon flush, the reaction mixture was heated at 100° C. for 1 h. Analysis of the reaction mixture by LCMS showed complete conversion to the desired product. The mixture was cooled down to room temperature and filtered. The filtrate was concentrated under reduced pressure to afford 129b (300 mg, 87%) as a dark oil, which was used in next step without further purification. MS-ESI: [M+H]+ 573.3

Aufarbeitung

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureThe mixture was cooled down to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-8733eb86b2c445dd88c3af5c332d816c
Quelldatensatz
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08669251B2

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