Water → 16-Azidohexadecanoic acid

Participants

Reaction Conditions

Reaction Steps

To the suspension of 16-hydroxyhexadecanoic acid (0.7 g) in dichloromethane (20 ml) was added triethylamine (1.80 ml). Methanesulfonyl chloride (0.8 ml) was added dropwise to the reaction mixture while it was ice-cooled and stirred. Stirring was continued directly at 0° C. for 1 hour. The reaction mixture was extracted with chloroform, and the chloroform layer was washed with 1% aqueous sodium hydrogen carbonate and then with water, dried with anhydrous sodium sulfate and concentrated. The residue was subjected to chromatography on a silica gel column with an eluent system of chloroform-methanol (3:1) to give 16-methanesulfonyloxyhexadecanoic acid (0.74 g). To 16-methanesulfonyloxyhexadecanoic acid (325 mg) dissolved in N,N-dimethylformamide (DMF, 15 ml) was added sodium azide (268 mg), and the mixture was stirred at 80° C. for 12 hours. The reaction mixture, after having been cooled, was then distributed into ethyl acetate and water, and the ethyl acetate layer was dried over anhydrous sodium sulfate to give 16-azidohexadecanoic acid (235 mg). To the solution of 16-azidohexadecanoic acid (226 mg) in DMF were added N-hydroxysuccinimide (90 mg) and N,N'-dicyclohexylcarbodiimide (160 mg), and the mixture was stirred for 48 hours. The reaction mixture was filtered and concentrated to give the active ester of 16-azidohexadecanoic acid. To the active ester dissolved in DMF were further added 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (310 mg) and triethylamine (1 ml), and the mixture was stirred for 24 hours. The solvent was removed by distillation, and the residue was subjected to chromatography on a silica gel column with an eluent system of chloroform-methanol (6:1) to give SPK226 in the yield of 92 mg.

Provenance & Evidence