Boron trifluoride etherate → HCID 131729971, compound

Participants

Reaction Steps

The synthesis of a BODIPY-FTY720 conjugate 1 started with the Wittig reaction of 15 and aldehyde 16 using potassium tert-butoxide as the base (Scheme 1). The resulting bromide 17 was subjected to a Sonogashira reaction with 5-benzyloxy-1-pentyne to give 18 in 53% yield. The double and triple bonds were hydrogenated and the benzyl group was removed by hydrogenolysis with palladium hydroxide in methanol. The ketal protecting group was also partially removed under these conditions, but it was easily reinstalled by treating the resulting mixture with 2,2-dimethoxypropane in the presence of 10-camphorsulfonic acid to give 19 in 72% yield. After conversion of the hydroxy group in 19 to the mesylate and treatment with sodium azide in dimethylformamide (DMF), azide 20 was obtained in 67% yield. The click reaction of azide 20 with BODIPY-alkyne 22 catalyzed by cuprous iodide in DMF at room temperature gave protected BODIPY-FTY720 triazole-linked conjugate 21 in 75% yield. Finally, deprotection of both the ketal and Boc protecting groups in one pot was achieved by treatment of 21 with boron trifluoride etherate (BF3.OEt2) in the presence of 4 Å molecular sieves in dichloromethane at 0° C. to afford BODIPY-FTY720 conjugate 1 in 61% yield.

Provenance & Evidence