Water → Dasabuvir

HRID 58412

Reaction equation

HRID 58412 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.C(O)(CC)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CS(O[C:55]1[CH:64]=[CH:63][C:62]2[C:57](=[CH:58][CH:59]=[C:60]([C:65]3[CH:70]=[C:69]([N:71]4[CH:76]=[CH:75][C:74](=[O:77])[NH:73][C:72]4=[O:78])[CH:68]=[C:67]([C:79]([CH3:82])([CH3:81])[CH3:80])[C:66]=3[O:83][CH3:84])[CH:61]=2)[CH:56]=1)(=O)=O.[CH3:85][S:86]([NH2:89])(=[O:88])=[O:87]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:79]([C:67]1[C:66]([O:83][CH3:84])=[C:65]([C:60]2[CH:61]=[C:62]3[C:57](=[CH:58][CH:59]=2)[CH:56]=[C:55]([NH:89][S:86]([CH3:85])(=[O:88])=[O:87])[CH:64]=[CH:63]3)[CH:70]=[C:69]([N:71]2[CH:76]=[CH:75][C:74](=[O:77])[NH:73][C:72]2=[O:78])[CH:68]=1)([CH3:82])([CH3:81])[CH3:80]

Participants

8

Reactant 6

HCID 962WaterHCID 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 866938706-(3-tert-Butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl methanesulfonate

Product 1

HCID 56640146Dasabuvir

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

Palladium acetate (0.0018 g, 8.09 μmol), di-tert-butyl(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (0.0086 g, 0.018 mmol) and water (0.6 μL, 0.032 mmol) were charged to a 40-mL reaction vial inside an inert atmosphere glove box. tert-Amyl alcohol (1.0 mL) was added, and the contents were heated to 80° C. and stirred at this temperature for 15 minutes. The reaction mixture was cooled down to room temperature. Potassium phosphate tribasic (0.094 g, 0.445 mmol), 6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl methanesulfonate (0.2 g, 0.404 mmol), methanesulfonamide (0.046 g, 0.485 mmol) and tert-amyl alcohol (1.5 mL) were added to the 40-mL reaction vial. The reaction temperature was raised to 110° C., and the contents were stirred for 14 hours. HPLC analysis of the reaction mixture showed that the titled compound was formed in 5 area % at 210 nm.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. temperatureThe reaction temperature was raised to 110° C.
  3. stirringthe contents were stirred for 14 hours

Sources & evidence

ORD record
ord-39da1c7c7b66483db7b62b2fd84a1c9a
Source dataset
uspto-grants-2016_09
Patent number
US09434698B2

Linked notes

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