Trimethylsilyl triflate → (2R,3R,4S,5S)-4-(Benzoyloxy)-2-(2-cyano-6-[(1-naphthylmethyl)amino]-9H-purin-9-yl}-5-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate

HRID 1293060

반응식

HRID 1293060 반응식
N1(C2CCCCCCCCCC2)CCCCCCCCCN1.[C:23]1([CH2:33][NH:34][C:35]2[N:43]=[C:42]([C:44]#[N:45])[N:41]=[C:40]3[C:36]=2[N:37]=[CH:38][NH:39]3)[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1.[C:46]([O:54][C@H:55]1[C@@H:59]([O:60][C:61](=[O:68])[C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[C@@H:58](OC(=O)C)[O:57][C@@H:56]1[C:73]([NH:75][CH2:76][CH3:77])=[O:74])(=[O:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=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>C(#N)C.C(OCC)(=O)C>[C:61]([O:60][C@@H:59]1[C@H:55]([O:54][C:46](=[O:53])[C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C@@H:56]([C:73]([NH:75][CH2:76][CH3:77])=[O:74])[O:57][C@H:58]1[N:39]1[CH:38]=[N:37][C:36]2[C:40]1=[N:41][C:42]([C:44]#[N:45])=[N:43][C:35]=2[NH:34][CH2:33][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)(=[O:68])[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1

참가 물질

8

반응물 5

HCID 65367Trimethylsilyl triflateHCID 57346892DiazabicycloundecaneHCID 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 benzoateHCID 1785105996-[(1-naphthylmethyl)amino]-9H-purine-2-carbonitrile

생성물 1

HCID 60018577(2R,3R,4S,5S)-4-(Benzoyloxy)-2-(2-cyano-6-[(1-naphthylmethyl)amino]-9H-purin-9-yl}-5-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

Diazabicycloundecane (0.18 ml, 1.2 mmol) was added to a solution of (6-[(1-naphthylmethyl)amino]-9H-purine-2-carbonitrile (200 mg, 0.67 mmol) (Preparation 10) and (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 (309 mg, 0.70 mmol) (Preparation 18) in acetonitrile (5 ml). Trimethylsilyl trifluoromethanesulfonate (0.24 ml, 1.33 mmol) was added and the reaction mixture heated under reflux for 30 minutes. The reaction mixture was then allowed to cool to room temperature, diluted with ethyl acetate (20 ml) and washed twice with water (20 ml). The ethyl acetate layer was then washed with 10% w/w aqueous citric acid and saturated aqueous sodium chloride solution (20 ml). The organic phase was dried over anhydrous magnesium sulphate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane increasing in polarity to dichloromethane:methanol (98:2 by volume). The solvent was removed under reduced pressure to give the title compound (235 mg) as a foam.

후처리

  1. temperaturethe reaction mixture heated
  2. temperatureunder reflux for 30 minutes
  3. washwashed twice with water (20 ml)
  4. washThe ethyl acetate layer was then washed with 10% w/w aqueous citric acid and saturated aqueous sodium chloride solution (20 ml)
  5. dry with materialThe organic phase was dried over anhydrous magnesium sulphate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane increasing in polarity to dichloromethane:methanol (98:2 by volume)
  8. customThe solvent was removed under reduced pressure

출처 및 근거

ORD 기록
ord-9ce78a26916649658ca0a392e79ba739
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07238676B2

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