Ammonia → (2R,3R,4S,5R)-2-(2-(Aminomethyl)-6-{[2,2-bis(4-chlorophenyl)ethyl]amino}-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol

HRID 1293053Notes

Reaction equation

HRID 1293053 reaction equation
C([O:4][C@H:5]1[C@@H:9]([O:10]C(=O)C)[C@H:8]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([C:40]#[N:41])=[N:18][C:19]=3[NH:23][CH2:24][CH:25]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=2)[C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[O:7][C@@H:6]1[CH2:42][O:43]C(=O)C)(=O)C.N.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.[Pd]>[NH2:41][CH2:40][C:17]1[N:16]=[C:15]2[C:20]([N:21]=[CH:22][N:14]2[C@H:8]2[C@H:9]([OH:10])[C@H:5]([OH:4])[C@@H:6]([CH2:42][OH:43])[O:7]2)=[C:19]([NH:23][CH2:24][CH:25]([C:33]2[CH:34]=[CH:35][C:36]([Cl:39])=[CH:37][CH:38]=2)[C:26]2[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=2)[N:18]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 10340Sodium CarbonateHCID 60018583(2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-{[2,2-bis(4-chlorophenyl)ethyl]amino}-2-cyano-9H-purin-9-yl)tetrahydro-3-furanyl acetate

Product 1

HCID 60018575(2R,3R,4S,5R)-2-(2-(Aminomethyl)-6-{[2,2-bis(4-chlorophenyl)ethyl]amino}-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiolYield 50.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-{[2,2-bis(4-chlorophenyl)ethyl]amino}-2-cyano-9H-purin-9-yl)tetrahydro-3-furanyl acetate (700 mg, 1 mmol) (Preparation 64) in ethanol (20 ml) was saturated with ammonia gas. 10% Palladium on carbon (140 mg) was added and the reaction mixture stirred under an atmosphere of hydrogen gas (414 kPa, 60 psi) at room temperature for 16 hours. The Palladium on carbon was filtered off through Arbocel (Trade Mark) and the filtrate was evaporated under reduced pressure. The residue was dissolved in methanol (50 ml) and sodium carbonate (60 mg, 0.57 mmol) was added. The reaction mixture was stirred for 1.5 hours and then 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 in polarity to dichloromethane:methanol:0.88 concentrated aqueous ammonia (90:10:2 by volume). The solvent was removed under reduced pressure to give the title compound (275 mg) as a foam.

Workup

  1. filtrationThe Palladium on carbon was filtered off through Arbocel (Trade Mark)
  2. customthe filtrate was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in methanol (50 ml)
  4. stirringThe reaction mixture was stirred for 1.5 hours
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane
  7. temperaturemethanol:0.88 concentrated aqueous ammonia (95:5:0.5 by volume) increasing in polarity to dichloromethane
  8. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-53aabcfe0dcb479089217aeb93a8607c
Source dataset
uspto-grants-2007_07
Patent number
US07238676B2

Reaction notes

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