2-Methyltetrahydrofuran → Dasabuvir

HRID 1049654Notes

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+].CC1CCCO1.FC(F)(F)C(F)(S(O[C:60]1[CH:69]=[CH:68][C:67]2[C:62](=[CH:63][CH:64]=[C:65]([C:70]3[CH:75]=[C:74]([N:76]4[CH:81]=[CH:80][C:79](=[O:82])[NH:78][C:77]4=[O:83])[CH:73]=[C:72]([C:84]([CH3:87])([CH3:86])[CH3:85])[C:71]=3[O:88][CH3:89])[CH:66]=2)[CH:61]=1)(=O)=O)C(F)(F)F.[CH3:93][S:94]([NH2:97])(=[O:96])=[O:95]>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:84]([C:72]1[C:71]([O:88][CH3:89])=[C:70]([C:65]2[CH:66]=[C:67]3[C:62](=[CH:63][CH:64]=2)[CH:61]=[C:60]([NH:97][S:94]([CH3:93])(=[O:96])=[O:95])[CH:69]=[CH:68]3)[CH:75]=[C:74]([N:76]2[CH:81]=[CH:80][C:79](=[O:82])[NH:78][C:77]2=[O:83])[CH:73]=1)([CH3:86])([CH3:87])[CH3:85]

Participants

Conditions

Temperature: 80 °C

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (0.0071 g, 7.71 μmol), di-tert-butyl(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (0.0089 g, 19.0 μmol) and milled potassium phosphate tribasic (0.360 g, 1.696 mmol) were charged to a 40-mL reaction vial inside an inert atmosphere glove box. 2-Methyltetrahydrofuran (4 mL) was added, and the closed vial and its contents were heated to 80° C. with magnetic stirring 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 1,1,1,2,3,3,3-heptafluoropropane-2-sulfonate (1.0 g, 1.542 mmol, Example 3-4, compound (5c)), methanesulfonamide (0.176 g, 1.850 mmol) and ethyl acetate (8 mL) were added to the 40-mL reaction vial. The temperature of the closed vial and its contents was raised to 90° C. and stirred for 20 hours. HPLC analysis of the reaction mixture showed that the product was formed in 95 area % at 210 nm.

Workup

additionwere charged to a 40-mL reaction vial inside an inert atmosphere glove box
temperatureThe reaction mixture was cooled down to room temperature
temperatureThe temperature of the closed vial and its contents was raised to 90° C.
stirringstirred for 20 hours
customwas formed in 95 area % at 210 nm

Sources & evidence

ORD record: ord-f0b79791432b4cda88b6816e25754615
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09381508B2

Reaction notes

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