Diethanolamine → HCID 54077422, compound

Participants

Reaction Steps

The mixture of diethanolamine (2.1 g, 20 mmol), H2O (50 ml) and diethyl vinylphosphonate (3.3 g, 20 mmol) was stirred at room temperature overnight. The solvent was evaporated and the residue codistilled with ethanol. The residue was purified by chromatography on silica gel (CHCl3-MeOH) to obtain diethyl 2-(bis(2-hydroxyethyl)amino)ethylphosphonate, yield 5.03 g (93%). This intermediate (3.4 g, 12.6 mmol) was dissolved in CH2Cl2 (50 ml), a catalytic amount of dimethylaminopyridine was added followed by Et3N (1.2 ml) and then tritylchloride (3.5 g, 14.5 mmol) dissolved in CH2Cl2 (30 ml) was added drop-wise. The reaction mixture was stirred overnight at room temperature and solvent evaporated. The residue was purified by column chromatography on silica gel (CHCl3-MeOH) to afford diethyl 2((2-hydroxyethyl)(2-(trityloxy)ethyl)amino)ethylphosphonate as yellowish oil (6.01 g, 93%). To a solution of triphenylphosphine (6.3 g, 24 mmol) in dry THF (100 ml) cooled to −30° C. under argon atmosphere diisopropylazadicarboxylate (DIAD, 4.4 ml, 23 mmol) was added slowly. The mixture was stirred for 30 minutes and this preformed complex was added to 2-amino-6-chloropurine (3.8 g, 22.6 mmol), dry THF (70 ml) and diethyl 2-((2-hydroxyethyl)(2-(trityloxy)ethyl)amino)ethylphosphonate (5.72 g, 11.2 mmol) at −30° C. under argon. The resulting mixture was slowly warmed to room temperature and stirred for 48 h. Then water (30 ml) was added and the mixture was heated at 80° C. for 30 h. Solvent was evaporated the residue was codistilled with toluene or ethanol and the crude mixture purified by chromatography on silica gel (MeOH—CHCl3). This intermediate was dissolved in trifluoroacetic acid (aqueous, 75%, 20 ml) and stirred overnight. The solvent was evaporated and the residue codistilled with water (3×) and ethanol. After chromatography on silica gel (MeOH—CHCl3) the diethyl 9-[(N-(2-hydroxyethyl)-N-(2-phosphonoethyl))-2-aminoethyl]guanine was obtained in 50% yield (2.25 g).

Provenance & Evidence