2',6'-DiMethylcarbonylphenyl-10-sulfopropylacridiniuM-9-carboxylate 4'-NHS Ester synthesis

Yield:194357-64-7 56%

Reaction Conditions:

in 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate at 155; for 16 h;

Steps:

4

Example 4; [0081] N-Alkvation on a half- gram scale of 2^>.6-dimethyl-4'-N- succinimidyloxycarbonylphenyl acridine-9-carboxylate with propane sultone in [BMIMl[PFoI: Synthesis of 26'-dimethyl-4'-N-succinimidyloxycarbonylphenyl-10- sulfopropylacridinium-9-carboxylate (NSP-DMAE-NHS).; [0082] To an 8 dram vial was added 0.50 g (1.07 mmol) of 2',6-dimethyl-4'-N- succinimidyloxycarbonylphenyl acridine-9-carboxylate, 5 g (17.6 mmol) of l-butyl-3- methylimidazolium hexafluorophosphate [BMIM]PF₆] (Fluka) and 1.31 g (10.7 mmol) of distilled 1,3-propanesultone under nitrogen. This sealed vial was heated to 155⁰C for 16 hours. Then the reaction mixture was cooled to 4O⁰C and added drop wise to 100 ml of ethyl acetate with stirring which gave a yellow precipitate. The mixture was stirred at room temperature for 2 hours and filtered. The filter cake was washed with ethyl acetate (30 ml x 2) and dried under high vacuum which gave 0.753 of a yellow solid. The crude product was purified by preparative HPLC on Waters system using an YMC, C 18 column, 50 x 500 mm, with a solvent flow rate of 60 ml/minute, UV detection at 260 nm, elution being performed with 35%B over 50 minutes (A: water/0.05%TFA; B: acetonitrile/0.05%TFA). After lyophilization of the HPLC fractions, the desired product NSP-DMAE-NHS ester, 0.356 g (56% yield), was obtained as a yellow powder.

References:

WO2009/67417,2009,A1 Location in patent:Page/Page column 28