4-Toluenesulfonyl chloride → HCID 66958565, compound

Participants

Reaction Steps

mCPBA (2.55 g of 77%, 11.38 mmol) was added to a suspension of 9-(methylsulfonyl)-9,10,11,12-tetrahydro-8H-[1,4]diazepino[1′,2′:1,2]imidazo[4,5-c]quinoline (3.0 g, 9.5 mmol) in chloroform, and the reaction was stirred for 30 minutes at ambient temperature. The reaction was incomplete as determined by LC/MS analysis. Additional mCPBA (approximately 0.5 equivalent) was added twice, and the reaction was stirred overnight. The solvent was removed under reduced pressure, and a solution of potassium hydroxide in methanol was added to adjust to pH 7.5. The methanol was removed under reduced pressure, and residue was dissolved in chloroform. Additional mCPBA (1.2 equivalents) was added, and the reaction was stirred for two hours. Additional mCPBA was added, and the reaction was stirred overnight at ambient temperature. Ammonium hydroxide (15 mL) and p-toluenesulfonyl chloride (1.99 g, 10.4 mmol) were added, and the reaction was stirred at ambient temperature for two hours. The organic layer was separated, concentrated under reduced pressure, and purified by normal phase preparative HPLC on silica gel (eluting with 2 N ammonia in methanol/chloroform in a 42-minute gradient from 0:100 to 25:75). The resulting solid was recrystallized from 5:2:1 acetonitrile/ethanol/methanol to provide 9-(methylsulfonyl)-5-oxido-9,10,11,12-tetrahydro-8H-[1,4]diazepino[1′,2′:1,2]imidazo[4,5-c]quinoline, which was dissolved in chloroform, treated with ammonium hydroxide and p-toluenesulfonyl chloride, and purified by chromatography and recrystallization again as described above to provide 161 mg of 9-(methylsulfonyl)-9,10,11,12-tetrahydro-8H-[1,4]diazepino[1′,2′:1,2]imidazo[4,5-c]quinolin-6-amine as a white powder, mp 280° C.

Provenance & Evidence