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

HRID 897109

반응식

HRID 897109 반응식
[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.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[C:24]([O:32][C@H:33]1[C@@H:37]([O:38][C:39](=[O:46])[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C@@H:36](OC(=O)C)[O:35][C@@H:34]1[C:51]([NH:53][CH2:54][CH3:55])=[O:52])(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(O[C@H]1[C@@H](OC(=O)C2C=CC=CC=2)[C@H](OC(=O)C)O[C@@H]1C(NCC)=O)(=O)C1C=CC=CC=1.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>ClC(Cl)(Cl)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:39]([O:38][C@@H:37]1[C@H:33]([O:32][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:34]([C:51]([NH:53][CH2:54][CH3:55])=[O:52])[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:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

참가 물질

9

반응물 5

HCID 65367Trimethylsilyl triflateHCID 53603492-Amino-6-chloropurineHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 69018799(2S,3S,4R,5S)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoateHCID 69431969(2S,3S,4R,5R)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate

생성물 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

시약·촉매·용매 3

HCID 1140Toluene용매HCID 62781,1,1-Trichloroethane용매HCID 8857Ethyl Acetate용매

실험 절차

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)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate and (2S,3S,4R,5S)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate (Preparation 18) (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) and then brine (350 ml). The organic layer was separated, dried over anhydrous magnesium sulphate, 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).

후처리

  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 sulphate
  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)

출처 및 근거

ORD 기록
ord-219fc9c866fd4c9487b7ef4c8dd9e740
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921753B2

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