Trifluoroacetic acid → (S)-2-amino-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy]-6-methoxypurine

HRID 6270Notes

Reaction equation

HRID 6270 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15](C(OC(C)(C)C)=O)[C:16]1[N:24]=[C:23]2[C:19]([N:20]=[CH:21][N:22]2[O:25][CH2:26][C@@H:27]([O:37][CH2:38][P:39]([O:44][CH2:45][CH3:46])([O:41][CH2:42][CH3:43])=[O:40])[CH2:28][O:29]CC2C=CC=CC=2)=[C:18]([O:47][CH3:48])[N:17]=1)=O)(C)(C)C.ClCCl.CO>ClCCl.[Pd]>[NH2:15][C:16]1[N:24]=[C:23]2[C:19]([N:20]=[CH:21][N:22]2[O:25][CH2:26][C@@H:27]([O:37][CH2:38][P:39]([O:41][CH2:42][CH3:43])([O:44][CH2:45][CH3:46])=[O:40])[CH2:28][OH:29])=[C:18]([O:47][CH3:48])[N:17]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 21226129Dichloromethane methanol2×HCID 53696618(S)-2-[bis-(t-butoxycarbonyl)amino]-9-[3-benzyloxy-2-(diethoxyphosphorylmethoxy)propoxy]-6-methoxypurine

Product 1

HCID 54289305(S)-2-amino-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy]-6-methoxypurineYield 69.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (2 ml) was added to an ice cooled solution of (S)-2-[bis-(t-butoxycarbonyl)amino]-9-[3-benzyloxy-2-(diethoxyphosphorylmethoxy]propoxy]-6-methoxypurine (1.65 g, 2.3 mmol) in dry dichloromethane (30 ml) an the resulting solution left for 2 hours. After warming to ambient temperature, 10% Pd-C (800 mg) was added and the mixture hydrogenated at ambient temperature and pressure for 2 hours. The reaction mixture was filtered, the catalyst washed with dichloromethane (20 ml), the filtrate washed with saturated aqueous sodium bicarbonate solution, brine, dried (MgSO4) and evaporated to leave a colourless viscous oil. Chromatography of the oil on silica gel using dichloromethane/methanol 95:5 as the initial eluant, then changing the eluant to dichloromethane/methanol 90:10 gave (S)-2-amino-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy]-6-methoxypurine as a colourless oil (0.65 g, 67%). IR: νmax (film) 3360, 3230, 2990, 2940, 2910, 1620, 1585, 1500, 1485, 1455, 1390, 1335, 1265, 1240, 1165, 1120, 1060, 1025, 975, 825, 785 cm-1. 1H NMR: δH [(CD3)2SO] 1.23 (6H, t, J=7 Hz, (OCH2CH3)2), 3.45-3.60 (2H, m, collapses to d on D2O exchange, CH2OH), 3.70-3.85 (1H, m, CH), 3.96 (3H, s, OCH3), 3.9-4.15 (6H, m, (OCH2CH3, OCH2P), 4.31 (1H, dd, J=11.3 Hz, J=6.9 Hz, NOCHB), 4.45 (1H, dd, J =11.3 Hz, J=3 Hz, NOCHA), 4.84 (1H, t, J=5.5 Hz, D2O exchangeable OH), 6.59 (2H, br.s, D2O exchangeable NH2), 8.14 (3H, s, H-8). m/z: (FAB, thioglycerol matrix) 406 (MH+).

Workup

  1. waitthe mixture hydrogenated at ambient temperature and pressure for 2 hours
  2. filtrationThe reaction mixture was filtered
  3. washthe catalyst washed with dichloromethane (20 ml)
  4. washthe filtrate washed with saturated aqueous sodium bicarbonate solution, brine
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto leave a colourless viscous oil

Sources & evidence

ORD record
ord-4ec7e441b65e463e8f7ca2919ba87390
Source dataset
uspto-grants-1993_09
Patent number
US05247085

Reaction notes

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