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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-dihydropyridazin-3-yl)pyridin-3-yl)methyl Acetate

HRID 1185168
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1185168
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[O:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:17]([O:20][CH2:21][C:22]1[C:23]([N:37]2[N:46]=[CH:45][C:44]3[C:39](=[C:40]([F:51])[CH:41]=[C:42]([C:47]([CH3:50])([CH3:49])[CH3:48])[CH:43]=3)[C:38]2=[O:52])=[N:24][CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1)(=[O:19])[CH3:18].C([O-])(=O)C.[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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:17]([O:20][CH2:21][C:22]1[C:23]([N:37]2[N:46]=[CH:45][C:44]3[C:39](=[C:40]([F:51])[CH:41]=[C:42]([C:47]([CH3:49])([CH3:48])[CH3:50])[CH:43]=3)[C:38]2=[O:52])=[N:24][CH:25]=[CH:26][C:27]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[O:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:19])[CH3:18]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 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 acetateHCID 866840236-Chloro-2-methyl-4-(5-methylisoxazol-3-ylamino)pyridazin-3(2H)-one

Produkt 1

HCID 86684024
(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methylisoxazol-3-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl Acetate
Ausbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 141a (288 mg, 1.2 mmol), 3-(acetoxymethyl)-2-(6-tert-butyl-8-fluoro-1-oxo-phthalazin-2(1H)-yl)pyridin-4-ylboronic acid 116c (1.49 g, 3.6 mmol), Pd(dppf)Cl2 (99 mg, 0.12 mmol), potassium acetate (235 mg, 2.4 mmol), K3PO4 (523 mg, 2.4 mmol), acetonitrile (20 mL), and water (10 drops). After three cycles of vacuum/argon flush, the mixture was heated at 95° C. for 2 h. It was then filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:1 ethyl acetate/petroleum ether to afford 141b (220 mg, 32%) as a yellow solid. MS-ESI: [M+H]+ 574.2

Aufarbeitung

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 1:1 ethyl acetate/petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-9a926380168f4dae8cb1420c4d04e6ce
Quelldatensatz
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08669251B2

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