Acetamide → N-(4-(4-(4-phenylphthalazin-1-ylamino)phenoxy)quinolin-6-yl)acetamide

HRID 1042818Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1042818
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.O1CCOCC1.Br[C:50]1[CH:51]=[C:52]2[C:57](=[CH:58][CH:59]=1)[N:56]=[CH:55][CH:54]=[C:53]2[O:60][C:61]1[CH:66]=[CH:65][C:64]([NH:67][C:68]2[C:77]3[C:72](=[CH:73][CH:74]=[CH:75][CH:76]=3)[C:71]([C:78]3[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=3)=[N:70][N:69]=2)=[CH:63][CH:62]=1.[C:84]([NH2:87])(=[O:86])[CH3:85].C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].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:78]1([C:71]2[C:72]3[C:77](=[CH:76][CH:75]=[CH:74][CH:73]=3)[C:68]([NH:67][C:64]3[CH:65]=[CH:66][C:61]([O:60][C:53]4[C:52]5[C:57](=[CH:58][CH:59]=[C:50]([NH:87][C:84](=[O:86])[CH3:85])[CH:51]=5)[N:56]=[CH:55][CH:54]=4)=[CH:62][CH:63]=3)=[N:69][N:70]=2)[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=1

Komponenten

8

Edukt 5

HCID 178AcetamideHCID 11430Potassium CarbonateHCID 312751,4-Dioxane2×HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67317531N-(4-(6-bromoquinolin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine

Produkt 1

HCID 59427321N-(4-(4-(4-phenylphthalazin-1-ylamino)phenoxy)quinolin-6-yl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 86614170Pd(OAc)2 XantphosKatalysator

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

The title compound was prepared according to a method described in Garnier, E.; Andoux, J.; Pasquinet, E.; Suzenet, F.; Poullain, D.; Lebret, B.; Guillaumet, G. J. Org. Chem. 2004, 69, 7809. Xantphos (22 mg, 39 μmol) and 1,4-Dioxane (963 μl, 193 μmol) were added into a sealed tube. The tube was purged with argon, Palladium(II) acetate (4 mg, 19 μmol) was added, and the mixture was stirred under argon for 10 min. In a separate sealed tube, N-(4-(6-bromoquinolin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine (100 mg, 193 μmol), acetamide (57 mg, 963 μmol), potassium carbonate (798 mg, 5776 μmol), and 1,4-dioxane (963 μl, 193 μmol) were added. Then the Pd(OAc)2/Xantphos solution from the first tube was added with via syringe to the second tube. The resulting mixture was heated to 110° C. under an argon atmosphere with vigorous stirring until the halide disappeared. After 16 h, LCMS showed product at 1.324 as [M+H]+=498. The reaction was cooled to rt, quenched with water, extracted with CH2Cl2. The organic portions were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The product was purified by RPLC on the acidic Gilson workstation. To provide N-(4-(4-(4-phenylphthalazin-1-ylamino)phenoxy)quinolin-6-yl)acetamide. MS Calcd for C31H23N5O2: [M]+=497. Found: [M+H]+=498.

Aufarbeitung

  1. customThe title compound was prepared
  2. additionwas added
  3. customIn a separate sealed tube
  4. waitAfter 16 h
  5. temperatureThe reaction was cooled to rt
  6. customquenched with water
  7. extractionextracted with CH2Cl2
  8. washwashed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe product was purified by RPLC on the acidic Gilson workstation

Quellen und Nachweise

ORD-Eintrag
ord-b5f68b40d0804485a95708a6019910a8
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08557816B2

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