Trimethylsilyl triflate → (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy) methyl]-5-(6-[(2,2-diphenylethyl)amino]-2-{[(isobutylsulfonyl)amino]methyl}-9H-purin-9-yl)tetrahydro-3-furanyl acetate

HRID 1700096ノート

反応式

HRID 1700096 の反応式
Cl.[C:2]1([CH:8]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:9][NH:10][C:11]2[N:19]=[C:18]([CH2:20][NH:21][S:22]([CH2:25][CH:26]([CH3:28])[CH3:27])(=[O:24])=[O:23])[N:17]=[C:16]3[C:12]=2[N:13]=[CH:14][NH:15]3)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[C@@H:39]1[O:51][C@H:50]([CH2:52][O:53][C:54](=[O:56])[CH3:55])[C@@H:45]([O:46][C:47](=[O:49])[CH3:48])[C@H:40]1[O:41][C:42](=[O:44])[CH3:43])(=O)C.C[Si](OS(C(F)(F)F)(=O)=O)(C)C>ClC(Cl)(Cl)C.C(OCC)(=O)C>[C:47]([O:46][C@H:45]1[C@@H:40]([O:41][C:42](=[O:44])[CH3:43])[C@H:39]([N:15]2[CH:14]=[N:13][C:12]3[C:16]2=[N:17][C:18]([CH2:20][NH:21][S:22]([CH2:25][CH:26]([CH3:28])[CH3:27])(=[O:23])=[O:24])=[N:19][C:11]=3[NH:10][CH2:9][CH:8]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[O:51][C@@H:50]1[CH2:52][O:53][C:54](=[O:56])[CH3:55])(=[O:49])[CH3:48]

参加物

6

反応物 3

HCID 65367Trimethylsilyl triflateHCID 830641,2,3,5-Tetraacetyl-beta-D-ribofuranoseHCID 178455636HCID 178455636、化合物

生成物 1

HCID 69972041(2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy) methyl]-5-(6-[(2,2-diphenylethyl)amino]-2-{[(isobutylsulfonyl)amino]methyl}-9H-purin-9-yl)tetrahydro-3-furanyl acetate

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 N-({6-[(2,2-diphenylethyl)amino]-9H-purin-2-yl}methyl)-2-methyl-1-propanesulfonamide hydrochloride (Preparation 8) (0.21 g, 0.42 mmol) in 1,1,1-trichloroethane (10 ml) was treated with N,O-bis(trimethylacetamide) (0.6 ml, 2.45 mmol) and the mixture was heated under reflux for 2 hours. The solvent was removed under reduced pressure and the residue was azeotroped with toluene (×2). The residue was dissolved in toluene (10 ml) and treated with the β-D-ribofuranose-1,2,3,5-tetraacetate (0.16 g, 0.50 mmol) and trimethylsilyltriflate (0.1 ml, 0.5 mmol). The mixture was then heated at reflux for 4 hours. The mixture was diluted with ethyl acetate, washed sequentially with saturated aqueous sodium hydrogen carbonate solution and brine and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (98:2 by volume) gradually changing to dichloromethane:methanol (95:5 by volume) to afford the title compound as a 1:3 mixture of α-and β-anomers (188 mg).

後処理

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hours
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was azeotroped with toluene (×2)
  5. dissolutionThe residue was dissolved in toluene (10 ml)
  6. temperatureThe mixture was then heated
  7. temperatureat reflux for 4 hours
  8. washwashed sequentially with saturated aqueous sodium hydrogen carbonate solution and brine
  9. customevaporated under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (98:2 by volume)

出典と根拠

ORDレコード
ord-2499fbfdff40461fb2c01677042ad89b
出典データセット
uspto-grants-2002_02
特許番号
US06350735B1

反応ノート

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