Trimethylsilyl triflate → (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-[(2,2-diphenylethyl)amino]-2-{[({[2-(1-piperidinyl)ethyl]amino}carbonyl)amino]methyl}-9H-purin-9-yl)tetrahydro-3-furanyl acetate

HRID 1293023Notes

Reaction equation

HRID 1293023 reaction equation
[C:1]1([CH:7]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17]([CH2:19][NH:20][C:21]([NH:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[O:22])[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][NH:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:38]([O:41][C@H:42]1[C@@H:46]([O:47][C:48](=[O:50])[CH3:49])[C@H:45](OC(=O)C)[O:44][C@@H:43]1[CH2:55][O:56][C:57](=[O:59])[CH3:58])(=[O:40])[CH3:39].C[Si](OS(C(F)(F)F)(=O)=O)(C)C>ClC(Cl)(Cl)C.C(OCC)(=O)C>[NH3:9].[C:38]([O:41][C@H:42]1[C@@H:46]([O:47][C:48](=[O:50])[CH3:49])[C@H:45]([N:14]2[CH:13]=[N:12][C:11]3[C:15]2=[N:16][C:17]([CH2:19][NH:20][C:21]([NH:23][CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[O:22])=[N:18][C:10]=3[NH:9][CH2:8][CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:44][C@@H:43]1[CH2:55][O:56][C:57](=[O:59])[CH3:58])(=[O:40])[CH3:39]

Participants

7

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 830641,2,3,5-Tetraacetyl-beta-D-ribofuranoseHCID 178523406N-({6-[(2,2-Diphenylethyl)amino]-9H-purin-2-yl}methyl)-N'-[2-(1-piperidinyl)ethyl]urea

Product 2

HCID 222AmmoniaHCID 58904388(2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-[(2,2-diphenylethyl)amino]-2-{[({[2-(1-piperidinyl)ethyl]amino}carbonyl)amino]methyl}-9H-purin-9-yl)tetrahydro-3-furanyl acetateYield 132.1%

Reagents, catalysts & solvents 2

HCID 62781,1,1-TrichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

N,O-Bistrimethylsilylacetamide (0.34 ml, 1.4 mmol) was added to a stirred suspension of N-({6-[(2,2-diphenylethyl)amino]-9H-purin-2-yl}methyl)-N′-[2-(1-piperidinyl) ethyl]urea (100 mg, 0.2 mmol) (Preparation 5) in 1,1,1-trichloroethane (20 ml) at 50° C. The reaction mixture was stirred at this temperature for 30 minutes, allowed to cool to room temperature and then evaporated under reduced pressure. Toluene (5 ml) was added and the solvent was removed under reduced pressure. The residue was redissolved in toluene (20 ml) and (2R,3R,4R,5S)-4,5-bis(acetyloxy)-2-[(acetyloxy)methyl]tetrahydro-3-furanyl acetate (0.064 g, 0.2 mmol) and then trimethylsilyltrifluoromethanesulphonate (0.1 ml, 0.35 mmol) were added. The reaction mixture was then heated under reflux for 2 hours. The reaction was allowed to cool to room temperature and diluted with ethyl acetate (100 ml). The solution was washed with saturated aqueous sodium hydrogen carbonate solution (50 ml) and saturated aqueous sodium chloride solution (50 ml) and then dried over anhydrous magnesium sulphate. The solvent was removed to give a residue that was purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 concentrated aqueous ammonia (90:10:1 by volume) to give the title compound as an oil (100 mg).

Workup

  1. customevaporated under reduced pressure
  2. additionToluene (5 ml) was added
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe residue was redissolved in toluene (20 ml)
  5. temperatureThe reaction mixture was then heated
  6. temperatureunder reflux for 2 hours
  7. temperatureto cool to room temperature
  8. washThe solution was washed with saturated aqueous sodium hydrogen carbonate solution (50 ml) and saturated aqueous sodium chloride solution (50 ml)
  9. dry with materialdried over anhydrous magnesium sulphate
  10. customThe solvent was removed
  11. customto give a residue that
  12. customwas purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-ea6b9f0ae10e4f2592e118360883560a
Source dataset
uspto-grants-2007_07
Patent number
US07238676B2

Reaction notes

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