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 1700096Notes

Reaction equation

HRID 1700096 reaction equation
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]

Participants

6

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 830641,2,3,5-Tetraacetyl-beta-D-ribofuranoseHCID 178455636HCID 178455636, compound

Product 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

Reagents, catalysts & solvents 2

HCID 62781,1,1-TrichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-2499fbfdff40461fb2c01677042ad89b
Source dataset
uspto-grants-2002_02
Patent number
US06350735B1

Reaction notes

Loading…