2-Methyltetrahydrofuran → Dasabuvir

HRID 1774059

반응식

HRID 1774059 반응식
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]

참가 물질

8

반응물 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)ethanesulfonate2회

생성물 1

HCID 56640146Dasabuvir

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-911fb50efe3b4d288ef9326bd7240767
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255074B2

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