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:46][C@H:47]1[C@@H:51]([O:52][C:53](=[O:60])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C@@H:50](OC(=O)C)[O:49][C@@H:48]1[C:65]([NH:67][CH2:68][CH3:69])=[O:66])(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=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.C[Si](OS(C(F)(F)F)(=O)=O)(C)C>ClC(Cl)(Cl)C.C(OCC)(=O)C>[C:38]([O:46][C@H:47]1[C@@H:51]([O:52][C:53](=[O:60])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C@H:50]([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:49][C@@H:48]1[C:65]([NH:67][CH2:68][CH3:69])=[O:66])(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1Participants
Reactant 4
HCID 65367Trimethylsilyl triflate
HCID 69018799(2S,3S,4R,5S)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate
HCID 69431969(2S,3S,4R,5R)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate
HCID 178523406N-({6-[(2,2-Diphenylethyl)amino]-9H-purin-2-yl}methyl)-N'-[2-(1-piperidinyl)ethyl]ureaProduct 1
Reagents, catalysts & solvents 2
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). (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) and then trimethylsilyltrifluoromethanesulphonate (0.1 ml, 0.35 mmol) were added and the reaction mixture was heated under reflux for 2 hours. The reaction was then allowed to cool to room temperature and diluted with ethyl acetate (100 ml). The solution was washed with saturated aqueous sodium hydrogen carbonate solution (2×50 ml) and saturated aqueous sodium chloride solution (50 ml) and then dried (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 (95:5:0.5 by volume). This gave an impure oil (100 mg) which was used without further purification in subsequent experiments.
Workup
- customevaporated under reduced pressure
- additionToluene (5 ml) was added
- customthe solvent was removed under reduced pressure
- dissolutionThe residue was redissolved in toluene (20 ml)
- temperaturethe reaction mixture was heated
- temperatureunder reflux for 2 hours
- temperatureto cool to room temperature
- washThe solution was washed with saturated aqueous sodium hydrogen carbonate solution (2×50 ml) and saturated aqueous sodium chloride solution (50 ml)
- dry with materialdried (anhydrous magnesium sulphate)
- customThe solvent was removed
- customto give a residue that
- customwas purified by column chromatography on silica gel eluting with dichloromethane
Sources & evidence
- ORD record
- ord-dd85968d0c6c408e89e23ce68951f6d2
- Source dataset
- uspto-grants-2005_07
- Patent number
- US06921753B2
Linked notes
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