Nitrogen-oxygen bond containing acyclic nucleoside phosphonate, preparation method and application thereof
A technology of nucleoside phosphonate and nitrogen-oxygen bond, which is applied in the field of its preparation and acyclic nucleoside phosphonate compounds, can solve the problems of acyclic nucleoside phosphonate compounds that have not been seen yet, and achieve high yield High efficiency, good anti-inflammatory activity, simple synthesis method
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 19
[0036] Example 19-(2-(N-diethylphosphonomethoxy-benzamide) ethyl)-adenine
[0037] (A) Preparation of diethyl hydroxymethyl phosphate (2)
[0038] Add diethyl phosphite (10 mL, 77.7 mol), paraformaldehyde (2.33 g, 77.7 mol), triethylamine (1.1 mL, 7.77 mol), slowly heated to 55°C after mixing. Stirring at this temperature for about 0.5h, the reaction started, exothermic violently, and the temperature quickly rose to 90°C. Paraformaldehyde dissolved, the temperature dropped, and TLC (4% methanol:dichloromethane) detected that the reaction was complete. The reaction mixture was stirred for about 3 h at 70 °C.
[0039] (B) Preparation of p-toluenesulfonic acid methylene phosphonic acid diethyl ester (3)
[0040] The reaction mixture in step (A) was left untreated, dissolved in diethyl ether (100 mL), and triethylamine (10.8 mL, 77.7 mol) was added dropwise thereto at room temperature for about fifteen minutes to complete the dropwise addition. Then it was cooled to 0° C. in ...
Embodiment 2
[0062] (1) Preparation of 1-N-(6-bromohexane)-uracil (12)
[0063] Uracil (5 g, 44.61 mmol), HMDS (hexamethyldisilazane) (20 mL), catalytic amount of ammonium sulfate mixture was refluxed at about 120 °C until the mixture became clear. The excess HMDS was distilled off under reduced pressure, and the residual trace of HMDS was taken away with toluene to obtain a colorless oil. The resulting oil was dissolved in DMF (50 mL), and 1,6-dibromohexane (14 mL, 89.21 mmol) was added thereto. The reaction mixture was stirred at 80° C. for about 24 hours, followed by TLC (80% ethyl acetate:petroleum ether) until the reaction was complete. The reaction solution was concentrated under reduced pressure, and a large amount of white solid was precipitated after cooling. The solid was filtered and washed with a little ethyl acetate. The filtrates were combined, and the solvent was evaporated to dryness under reduced pressure to obtain a solid residue, which was separated on a silica gel co...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More