1H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)- → HCID 465659, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 300 mg N-(2-bromoethyl)-phthalimide (BEP) and 274 mg AZT in 1 ml of sieve-dried DMPU was treated with 300 ul of sodium methoxide solution (4.4M NaOMe in MeOH) and heated at 70° C. for one hour. Another 300 ul of NaOMe solution and 175 mg BEP were added and the solution again heated at 70° C. for a total of 3.5 hours. The reaction was followed by analytical TLC on silica gel-F 250 um using a solvent system of CHCl3 /MeOH/HOAc (95+5+0.5) and was found to be incomplete. Addition of more NaOMe solution and BEP did not increase the yield of the desired product. Unreacted BEP (Rf =0.81) and AZT (Rf =0.2) were identified using reference markers and by their UV spectra. The product (Rf =0.4) and a byproduct (Rf =0.62) were differentiated on the basis of their UV spectra and immunological activity. The reaction mixture was acidified with HOAc, diluted with 15 ml deionized water and extracted with EtOAc. The organic phase was washed with saturated NaCl solution, dried over Na2SO4, concentrated under reduced pressure and chromatographed by preparative TLC on silica gel-F 2000 um using the solvent system CHCl3 /MeOH/HOAc (96.5+3.3+0.3) and the product eluted with MeOH.

Provenance & Evidence