Toluene → (2R,3R,4S,5S)-2-(2-amino-6-chloro-9H-purin-9-yl)-4-(benzoyloxy)-5-[(ethylamino)carbonyl]-tetrahydro-3-furanyl benzoate

HRID 353638ノート

反応式

HRID 353638 の反応式
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([Cl:11])[N:3]=1.[CH3:12]/[C:13](/[O:19][Si](C)(C)C)=N\[Si](C)(C)C.[C:24]([O:32][CH:33]1[CH2:37][CH2:36][O:35][CH:34]1[C:38]([NH:40][CH2:41][CH3:42])=[O:39])(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.FC(F)(F)S(O[Si](C)(C)C)(=O)=[O:46].[C:55]1(C)C=[CH:59][CH:58]=[CH:57][CH:56]=1>ClC(Cl)(Cl)C.C(OCC)(=O)C>[C:13]([O:19][C@@H:37]1[C@H:33]([O:32][C:24](=[O:31])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C@@H:34]([C:38]([NH:40][CH2:41][CH3:42])=[O:39])[O:35][C@H:36]1[N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH2:1])=[N:3][C:4]=2[Cl:11])(=[O:46])[C:12]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1

参加物

8

反応物 5

HCID 1140TolueneHCID 65367Trimethylsilyl triflateHCID 53603492-Amino-6-chloropurineHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 700211312-[(Ethylamino)carbonyl]tetrahydro-3-furanyl benzoate

生成物 1

HCID 10143973(2R,3R,4S,5S)-2-(2-amino-6-chloro-9H-purin-9-yl)-4-(benzoyloxy)-5-[(ethylamino)carbonyl]-tetrahydro-3-furanyl benzoate

試薬・触媒・溶媒 2

HCID 62781,1,1-Trichloroethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A suspension of 2-amino-6-chloropurine (4.60 g, 27.13 mmol) in 1,1,1-trichloroethane (230 ml) was treated with N,O-bis(trimethylsilyl)acetamide (20 ml, 81.4 mmol). The mixture was heated under reflux for 6 hours. The solution was allowed to cool to room temperature and the solvent was removed under reduced pressure. The residue was treated with a solution of (2S,3S,4R,5R)- and (2S,3S,4R,5S)-5-acetyloxy)-4-benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate (Preparation 14) (14.39 g, 32.6 mmol) in anhydrous toluene (230 ml) and trimethylsilyl trifluoromethanesulfonate (20 ml, 108.5 mmol). The resulting solution was then heated at 90° C. under a nitrogen atmosphere for 90 minutes. The mixture was cooled to room temperature, diluted with ethyl acetate (250 ml) and washed with a saturated aqueous solution of sodium hydrogen carbonate (350 ml) then brine (350 ml). The organic layer was separated, dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (98:2 by volume) to afford the title compound as a foam (8.1 g).

後処理

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 6 hours
  3. customthe solvent was removed under reduced pressure
  4. temperatureThe resulting solution was then heated at 90° C. under a nitrogen atmosphere for 90 minutes
  5. temperatureThe mixture was cooled to room temperature
  6. washwashed with a saturated aqueous solution of sodium hydrogen carbonate (350 ml)
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (98:2 by volume)

出典と根拠

ORDレコード
ord-d88b11484aee483eae22dcd2dd2cad4e
出典データセット
uspto-grants-2004_06
特許番号
US06753322B2

反応ノート

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