Potassium Carbonate → 1-(4-Bromo-2-methylphenyl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[2-[(4-bromo-2-methylphenyl)amino]-4-chloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butan-1-ol (Reference Example 61; 1.10 g, 2.30 mmol) in tetrahydrofuran (20 mL) and triethylamine (1.6 mL) was added methanesulfonyl chloride (0.72 mL, 9.24 mmol) at 0° C. The mixture was stirred at 0° C. for 14 hr, and diluted with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. A mixture of the resulting mesylate, potassium carbonate (150 mg, 1.09 mmol) in N,N-dimethylformamide (15 mL) was stirred at 70° C. for 3 hr. The mixture was diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 0-30% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was purified by preparative HPLC to give a mixture contained the title compound as the trifluoroacetic acid salt. The trifluoroacetic acid salt was washed with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the title compound as a colorless amorphous (680 mg, 1.48 mmol, 64% in 2 steps).

Provenance & Evidence