反应详情

The method described in Koziara and Zwierzak, Tetrahedron Letters 28:6513-6516,1987 was followed to make CT1520. Briefly, boron trifluoride etherate (0.06 mol) was added dropwise at 10°-30° C. to a stirred solution of 1-(5-hydroxyhexyl)-3,7-dimethylxanthine (0.05 mol) and trimethylsilylazide (0.06 mol) in pentane (50 ml). After 24 hours at room temperature the mixture was poured into 100 mls of water. The organic phase was separated, washed with a 10% solution of sodium bicarbonate, and dried over sodium sulfate. The solution of the azide in pentane was stirred at 25°-30° C., and 0.05 mol of triethylphosphite was added. Stirring was continued for 6 hours, and the solution was left at this temperature for 72 hours. Solvent was evaporated off and the iminophosphorane was dissolved in ethanol (15 mls) and treated with p-toluenesulfonic acid monohydrate (0.05 mol) and water (0.05 mol). The mixture was refluxed for eight hours, evaporated and the residue diluted with 100 mls of ether. The tosyl salt of the amine was precipitated out and was recovered by filtration. Then, 30% aqueous ammonium hydroxide (20 mls) was added to the crystals and the free amine was extracted into dichloromethane (3×15 mls), dried over sodium sulfate and the solvent evaporated to yield the free amine as a viscous oil, 0.7 g with a 50% yield.

1. customThe organic phase was separated
2. washwashed with a 10% solution of sodium bicarbonate
3. dry with materialdried over sodium sulfate
4. stirringStirring
5. waitthe solution was left at this temperature for 72 hours
6. customSolvent was evaporated off
7. dissolutionthe iminophosphorane was dissolved in ethanol (15 mls)
8. temperatureThe mixture was refluxed for eight hours
9. customevaporated
10. additionthe residue diluted with 100 mls of ether
11. customThe tosyl salt of the amine was precipitated out and
12. filtrationwas recovered by filtration
13. additionThen, 30% aqueous ammonium hydroxide (20 mls) was added to the crystals
14. extractionthe free amine was extracted into dichloromethane (3×15 mls)
15. dry with materialdried over sodium sulfate
16. customthe solvent evaporated