2-Methyltetrahydrofuran → Dasabuvir

HRID 58409

Reaktionsgleichung

Reaktionsgleichung von HRID 58409
C(P(C(C)(C)C)C1C(OC)=CC=C(OC)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC1CCCO1.FC(F)(S(O[C:66]1[CH:75]=[CH:74][C:73]2[C:68](=[CH:69][CH:70]=[C:71]([C:76]3[CH:81]=[C:80]([N:82]4[CH:87]=[CH:86][C:85](=[O:88])[NH:84][C:83]4=[O:89])[CH:79]=[C:78]([C:90]([CH3:93])([CH3:92])[CH3:91])[C:77]=3[O:94][CH3:95])[CH:72]=2)[CH:67]=1)(=O)=O)C(F)(F)OC(F)(F)C(F)(F)F.[CH3:97][S:98]([NH2:101])(=[O:100])=[O:99]>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].C(OCC)(=O)C>[C:90]([C:78]1[C:77]([O:94][CH3:95])=[C:76]([C:71]2[CH:72]=[C:73]3[C:68](=[CH:69][CH:70]=2)[CH:67]=[C:66]([NH:101][S:98]([CH3:97])(=[O:100])=[O:99])[CH:75]=[CH:74]3)[CH:81]=[C:80]([N:82]2[CH:87]=[CH:86][C:85](=[O:88])[NH:84][C:83]2=[O:89])[CH:79]=1)([CH3:92])([CH3:91])[CH3:93]

Komponenten

8

Edukt 5

HCID 73012-MethyltetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 72879MethanesulfonamideHCID 44233348Di-tert-butyl(2',4',6'-triisopropyl-3,6-dimethoxy-(1,1'-biphenyl)-2-yl)phosphineHCID 866938676-(3-tert-Butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl 1,1,2,2-tetrafluoro-2-(perfluoroethoxy)ethanesulfonate2×

Produkt 1

HCID 56640146Dasabuvir

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Tris(dibenzylideneacetone)dipalladium(0) (0.0026 g, 2.80 μmol), di-tert-butyl(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (0.0033 g, 6.72 μmol) and milled potassium phosphate tribasic (0.131 g, 0.616 mmol) were charged to a 40-mL reaction vial inside an inert atmosphere glove box. 2-Methyltetrahydrofuran (1.5 mL) was added, the vial was capped, and the contents were heated to 80° C. and stirred at this temperature for 30 minutes. The reaction mixture was cooled down to room temperature. 6-(3-tert-Butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl 1,1,2,2-tetrafluoro-2-(perfluoroethoxy)ethanesulfonate (0.4 g, 0.560 mmol, Example 3-7, compound (5f)), methanesulfonamide (0.064 g, 0.672 mmol) and ethyl acetate (3 mL) were added to the 40-mL reaction vial. The temperature of the closed vial was raised to 90° C. and the contents were magnetically stirred for 16 hours. HPLC analysis of the reaction mixture showed that the product was formed in 97 area % at 210 nm.

Aufarbeitung

  1. additionwere charged to a 40-mL reaction vial inside an inert atmosphere glove box
  2. customthe vial was capped
  3. temperatureThe reaction mixture was cooled down to room temperature
  4. temperatureThe temperature of the closed vial was raised to 90° C.
  5. stirringthe contents were magnetically stirred for 16 hours
  6. customwas formed in 97 area % at 210 nm

Quellen und Nachweise

ORD-Eintrag
ord-347be5e3f37148b8bcd04cb41bf5f28e
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434698B2

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