Ammonia → (2S,3S,4R,5R)-5-(6-{[2,2-Bis(4-chlorophenyl)ethyl]amino}-2-{[({[2-(diisopropylamino)ethyl]amino}carbonyl)amino]methyl}-9H-purin-9-yl)-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamide

HRID 897082Notes

Reaction equation

HRID 897082 reaction equation
C([O:9][C@@H:10]1[C@H:14]([O:15]C(=O)C2C=CC=CC=2)[C@@H:13]([C:24]([NH:26][CH2:27][CH3:28])=[O:25])[O:12][C@H:11]1[N:29]1[CH:37]=[N:36][C:35]2[C:30]1=[N:31][C:32]([C:55]#[N:56])=[N:33][C:34]=2[NH:38][CH2:39][CH:40]([C:48]1[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][CH:49]=1)[C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=1)(=O)C1C=CC=CC=1.N.[CH:58]([N:61]([CH:72]([CH3:74])[CH3:73])[CH2:62][CH2:63][NH:64][C:65](N1C=CN=C1)=[O:66])([CH3:60])[CH3:59].N1C=CN=C1>C(O)C.[Pd].ClCCl.C(O)(C)C>[Cl:47][C:44]1[CH:43]=[CH:42][C:41]([CH:40]([C:48]2[CH:49]=[CH:50][C:51]([Cl:54])=[CH:52][CH:53]=2)[CH2:39][NH:38][C:34]2[N:33]=[C:32]([CH2:55][NH:56][C:65]([NH:64][CH2:63][CH2:62][N:61]([CH:72]([CH3:74])[CH3:73])[CH:58]([CH3:59])[CH3:60])=[O:66])[N:31]=[C:30]3[C:35]=2[N:36]=[CH:37][N:29]3[C@@H:11]2[O:12][C@H:13]([C:24]([NH:26][CH2:27][CH3:28])=[O:25])[C@@H:14]([OH:15])[C@H:10]2[OH:9])=[CH:46][CH:45]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 795ImidazoleHCID 21978296N-[2-(diisopropylamino)ethyl]-1H-imidazole-1-carboxamideHCID 60018584(2R,3R,4S,5S)-4-(Benzoyloxy)-2-(6-{[2,2-bis(4-chlorophenyl)ethyl]amino}-2-cyano-9H-purin-9-yl)-5-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate

Product 1

HCID 10283931(2S,3S,4R,5R)-5-(6-{[2,2-Bis(4-chlorophenyl)ethyl]amino}-2-{[({[2-(diisopropylamino)ethyl]amino}carbonyl)amino]methyl}-9H-purin-9-yl)-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamideYield 33.4%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

(2R,3R,4S,5S)-4-(Benzoyloxy)-2-(6-{[2,2-bis(4-chlorophenyl)ethyl]amino}-2-cyano-9H-purin-9-yl)-5-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate (220 mg, 0.28 mmol) (Preparation 68) was added to a saturated solution of ammonia in ethanol (15 ml). 10% Palladium on carbon (40 mg) was added and the suspension was stirred under an atmosphere of hydrogen gas (413.7 kPa, 60 psi) at room temperature for 16 hours. The reaction temperature was then stirred at 60° C. under an atmosphere of hydrogen gas (413.7 kPa, 50 psi) for a further 48 hours. The reaction mixture was filtered through Arbocel (Trade Mark) and the solvent was removed under reduced pressure. The crude residue was dissolved in toluene (8 ml) and isopropyl alcohol (2 ml) and N-[2-(diisopropylamino)ethyl]-1H-imidazole-1-carboxamide (50 mg, 0.21 mmol) (Preparation 27) were added. The solution was heated under reflux for 3 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 concentrated aqueous ammonia (90:10:2 by volume). The solvent was removed under reduced pressure give a product that was contaminated with imidazole. The product was dissolved in dichloromethane (60 ml) and the resulting solution was washed three times with water (50 mg) and dried over anhydrous magnesium sulphate. The solvent was removed under reduced pressure to give the title compound (53 mg) as a foam.

Workup

  1. stirringThe reaction temperature was then stirred at 60° C. under an atmosphere of hydrogen gas (413.7 kPa, 50 psi) for a further 48 hours
  2. filtrationThe reaction mixture was filtered through Arbocel (Trade Mark)
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe crude residue was dissolved in toluene (8 ml)
  5. temperatureThe solution was heated
  6. temperatureunder reflux for 3 hours
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by column chromatography on silica gel eluting with dichloromethane
  9. customThe solvent was removed under reduced pressure
  10. customgive a product that
  11. washthe resulting solution was washed three times with water (50 mg)
  12. dry with materialdried over anhydrous magnesium sulphate
  13. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-f4a809790e474a659d4a6df64fe8db79
Source dataset
uspto-grants-2005_07
Patent number
US06921753B2

Reaction notes

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