Benzyl mercaptan → 6-(Benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine

HRID 1473402

Reaktionsgleichung

Reaktionsgleichung von HRID 1473402
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](Cl)=[N:7][N:6]=[CH:5]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.CCN(C(C)C)C(C)C.[CH2:64]([SH:71])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1.[CH3:72][O:73][C:74]1[CH:79]=[C:78]([C:80]([F:83])([F:82])[F:81])[CH:77]=[CH:76][C:75]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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].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(Cl)Cl.O>[CH2:64]([S:71][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([C:75]1[CH:76]=[CH:77][C:78]([C:80]([F:83])([F:82])[F:81])=[CH:79][C:74]=1[O:73][CH3:72])=[N:7][N:6]=[CH:5]2)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

Komponenten

11

Edukt 6

HCID 7509Benzyl mercaptanHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 220304246-Bromo-1-chlorophthalazineHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acid

Produkt 1

HCID 866874486-(Benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazineAusbeute 43,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 178418807HCID 178418807, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of 6-bromo-1-chlorophthalazine (0.500 g, 2.053 mmol), Pd2(dba)3 (0.047 g, 0.051 mmol), Xantphos (0.059 g, 0.103 mmol), and n,n-diisopropylethylamine (1.076 ml, 6.16 mmol) in 6 mL of dioxane was heated to 60° C. and was treated with benzyl mercaptan (0.243 ml, 2.053 mmol) drop wise. After stirring for one hour, LC/MS showed product and bis coupled product. (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (0.407 g, 1.848 mmol), potassium carbonate (1.135 g, 8.21 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.168 g, 0.205 mmol), and 2 mL of water were added and the reaction mixture was heated to 80° C. overnight. LC/MS showed mostly product, so the reaction mixture was allowed to cool to room temperature. The aqueous layer was removed, and the organics were concentrated. Purification of the crude residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave 6-(benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine (0.340 g, 0.797 mmol, 38.8% yield). m/z (ESI) 427.2 (M+H)+

Aufarbeitung

  1. temperatureto cool to room temperature
  2. customThe aqueous layer was removed
  3. concentrationthe organics were concentrated
  4. customPurification of the crude residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-d9acc66ef21e415a80b17a51e6ebc392
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012443B2

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