2-Methyltetrahydrofuran → Dasabuvir

HRID 58410

反応式

HRID 58410 の反応式
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]

参加物

8

反応物 5

HCID 73012-MethyltetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 72879MethanesulfonamideHCID 44233348Di-tert-butyl(2',4',6'-triisopropyl-3,6-dimethoxy-(1,1'-biphenyl)-2-yl)phosphineHCID 866938686-(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-sulfonate2 回

生成物 1

HCID 56640146Dasabuvir

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-37110502d7ba4f61b00dde3d85b882c1
出典データセット
uspto-grants-2016_09
特許番号
US09434698B2

関連ノート

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