(S)-9-[3-benzyloxy-2-(diethoxyphosphorylmethoxy)propoxy]adenine → (S)-9-[2-(diethoxyphosphorylmethoxy)3-hydroxypropoxy]adenine

HRID 6273Notes

Reaction equation

HRID 6273 reaction equation
C([O:8][CH2:9][C@H:10]([O:23][CH2:24][P:25]([O:30][CH2:31][CH3:32])([O:27][CH2:28][CH3:29])=[O:26])[CH2:11][O:12][N:13]1[CH:21]=[N:20][C:19]2[C:14]1=[N:15][CH:16]=[N:17][C:18]=2[NH2:22])C1C=CC=CC=1>ClCCl.FC(F)(F)C(O)=O.N.[Pd]>[CH2:31]([O:30][P:25]([CH2:24][O:23][C@@H:10]([CH2:9][OH:8])[CH2:11][O:12][N:13]1[CH:21]=[N:20][C:19]2[C:14]1=[N:15][CH:16]=[N:17][C:18]=2[NH2:22])([O:27][CH2:28][CH3:29])=[O:26])[CH3:32]

Participants

6

Reactant 1

HCID 54040137(S)-9-[3-benzyloxy-2-(diethoxyphosphorylmethoxy)propoxy]adenine

Product 1

HCID 54312422(S)-9-[2-(diethoxyphosphorylmethoxy)3-hydroxypropoxy]adenine

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 222AmmoniaSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

10% Pd-C (50 mg) was added to a solution of (S)-9-[3-benzyloxy-2-(diethoxyphosphorylmethoxy)propoxy]adenine (0.21 g, 0.45 mmol) in dichloromethane (5 ml) and trifluoroacetic acid (lml) and the mixture hydrogenated at atmospheric pressure and ambient temperature for 5 hours. The mixture was filtered, the filtrate evaporated and the residue obtained dissolved in ethanolic ammonia solution (5 ml). After 15 minutes the solvent was evaporated and the residue chromatographed on silica gel using dichloromethane/methanol 90:10 as eluant. T.l.c. examination of the product indicated traces of a non UV absorbing impurity which was removed by prep. t.l.c. using dichloromethane/methanol 88:12 as eluant. (S)-9-[2-(diethoxyphosphorylmethoxy)3-hydroxypropoxy]adenine was obtained as a colourless gum (0.11 g, 65%). 1H NMR: δH [(CD3)2SO] 1.23 (6H, t, J=7 Hz, (OCH2CH3)2), 3.5-3.65 (2H, m, CH2OH), 3.75-3.85 (1H, m, CH), 3.98-4.15 (6H, m, OCH2P, (OCH2CH3)2), 4.38 (1H, dd, J=6.6 Hz, J=11.3 Hz, NOCHB), 4.54 (1H, dd, J=3 Hz, J=11.3 Hz, NOCHA), 4.88 (1H, t, J=5.5 Hz, D2O exchangeable OH), 7.38 (2H, br.s, D2O exchangeable NH2), 8.15 (1H, s, H-2 or H-8), 8.43 (1H, s, H-2 or H-8). m/z: (FAB+, thioglycerol matrix) 376 (MH+).

Workup

  1. filtrationThe mixture was filtered
  2. customthe filtrate evaporated
  3. customthe residue obtained
  4. customAfter 15 minutes the solvent was evaporated
  5. customthe residue chromatographed on silica gel
  6. customabsorbing impurity which
  7. customwas removed by prep

Sources & evidence

ORD record
ord-80bdae9dfd7846309df6346a394b17b5
Source dataset
uspto-grants-1993_09
Patent number
US05247085

Reaction notes

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