2-Methyl-2-butanol → Dasabuvir

HRID 1774056Notes

Reaction equation

HRID 1774056 reaction equation
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+].C(O)(CC)(C)C.FC(F)(S(O[C:65]1[CH:74]=[CH:73][C:72]2[C:67](=[CH:68][CH:69]=[C:70]([C:75]3[CH:80]=[C:79]([N:81]4[CH:86]=[CH:85][C:84](=[O:87])[NH:83][C:82]4=[O:88])[CH:78]=[C:77]([C:89]([CH3:92])([CH3:91])[CH3:90])[C:76]=3[O:93][CH3:94])[CH:71]=2)[CH:66]=1)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.[CH3:96][S:97]([NH2:100])(=[O:99])=[O:98]>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:89]([C:77]1[C:76]([O:93][CH3:94])=[C:75]([C:70]2[CH:71]=[C:72]3[C:67](=[CH:68][CH:69]=2)[CH:66]=[C:65]([NH:100][S:97]([CH3:96])(=[O:99])=[O:98])[CH:74]=[CH:73]3)[CH:80]=[C:79]([N:81]2[CH:86]=[CH:85][C:84](=[O:87])[NH:83][C:82]2=[O:88])[CH:78]=1)([CH3:91])([CH3:90])[CH3:92]

Participants

7

Reactant 5

HCID 64052-Methyl-2-butanol2×HCID 62657Potassium Phosphate, TribasicHCID 72879MethanesulfonamideHCID 44233348Di-tert-butyl(2',4',6'-triisopropyl-3,6-dimethoxy-(1,1'-biphenyl)-2-yl)phosphineHCID 566406691-Butanesulfonic acid, 1,1,2,2,3,3,4,4,4-nonafluoro-, 6-(5-(3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl)-3-(1,1-dimethylethyl)-2-methoxyphenyl)-2-naphthalenyl ester

Product 1

HCID 56640146Dasabuvir

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (0.0066 g, 7.16 μmol), di-tert-butyl(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (0.0083 g, 17 μmol) and milled potassium phosphate tribasic (0.334 g, 1.58 mmol) were charged to a 40-mL reaction vial inside an inert atmosphere glove box. t-Amyl alcohol (4 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 the room temperature. 6-(3-tert-Butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate (1.0 g, 1.43 mmol), methanesulfonamide (0.163 g, 1.72 mmol) and t-amyl alcohol (8 mL) were added to the 40-mL reaction vial, and the vial was capped. The reaction temperature was raised to 90° C. and the contents were stirred for 5 hours. HPLC analysis of the reaction mixture showed that the product was formed in 94 area % at 210 nm.

Workup

  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 the room temperature
  4. customthe vial was capped
  5. temperatureThe reaction temperature was raised to 90° C.
  6. stirringthe contents were stirred for 5 hours
  7. customwas formed in 94 area % at 210 nm

Sources & evidence

ORD record
ord-c2995e83f16043ec8e9d6844b70e37fe
Source dataset
uspto-grants-2016_02
Patent number
US09255074B2

Reaction notes

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