Toluene → (2S,3S,4R,5R)-5-{2-{[({[2-(Diisopropylamino)ethyl]amino}carbonyl)amino]methyl}-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamide

HRID 1293007Notes

Reaction equation

HRID 1293007 reaction equation
[CH:1]([N:4]([CH:15]([CH3:17])[CH3:16])[CH2:5][CH2:6][NH:7][C:8](N1C=CN=C1)=[O:9])([CH3:3])[CH3:2].[NH2:18][CH2:19][C:20]1[N:28]=[C:27]2[C:23]([N:24]=[CH:25][N:26]2[C@@H:29]2[O:33][C@H:32]([C:34]([NH:36][CH2:37][CH3:38])=[O:35])[C@@H:31]([OH:39])[C@H:30]2[OH:40])=[C:22]([NH:41][CH2:42][CH:43]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[N:21]=1.C(O)(C)C.C1(C)C=CC=CC=1>ClCCl.C(OCC)C>[CH:15]([N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6][NH:7][C:8]([NH:18][CH2:19][C:20]1[N:28]=[C:27]2[C:23]([N:24]=[CH:25][N:26]2[C@@H:29]2[O:33][C@H:32]([C:34]([NH:36][CH2:37][CH3:38])=[O:35])[C@@H:31]([OH:39])[C@H:30]2[OH:40])=[C:22]([NH:41][CH2:42][CH:43]([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[N:21]=1)=[O:9])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 1140TolueneHCID 3776IsopropanolHCID 21978296N-[2-(diisopropylamino)ethyl]-1H-imidazole-1-carboxamideHCID 59909598(2S,3S,4R,5R)-5-{2-(aminomethyl)-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamide

Product 1

HCID 10122714(2S,3S,4R,5R)-5-{2-{[({[2-(Diisopropylamino)ethyl]amino}carbonyl)amino]methyl}-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamideYield 44.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent3×

Procedure

N-[2-(Diisopropylamino)ethyl]-1H-imidazole-1-carboxamide (84 mg, 0.35 mmol) (Preparation 27) was added to a stirred suspension of (2S,3S,4R,5R)-5-{2-(aminomethyl)-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamide (100 mg, 0.23mmol) (Preparation 11) in dichloromethane (5 ml) at room temperature. The reaction was then heated to reflux and a drop of isopropanol was added to help dissolve the reagents. The reaction mixture was heated under reflux for 20 minutes and then toluene (5 ml) was added. The dichloromethane was boiled off and the reaction was then heated under reflux for 30 minutes. The reaction mixture was allowed to cool to room temperature and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol:0.88 concentrated aqueous ammonia (95:5:0.5 by volume increasing to 80:20:2 by volume). The solvent was removed under reduced pressure to give a yellow oil. The oil was dissolved in dichloromethane (2 ml) and diethylether was added to induce crystallisation. Filtration gave the title compound as a white solid (70 mg).

Workup

  1. temperatureThe reaction was then heated
  2. temperatureto reflux
  3. dissolutionto help dissolve the reagents
  4. temperatureThe reaction mixture was heated
  5. temperatureunder reflux for 20 minutes
  6. temperaturethe reaction was then heated
  7. temperatureunder reflux for 30 minutes
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane
  10. customThe solvent was removed under reduced pressure
  11. customto give a yellow oil
  12. customcrystallisation
  13. filtrationFiltration

Sources & evidence

ORD record
ord-6a104a1293a54adfaaa166e8dc2ef736
Source dataset
uspto-grants-2007_07
Patent number
US07238676B2

Reaction notes

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