Sodium Thiosulfate → HCID 22031222, compound

Participants

Reaction Steps

0.2 g of the mixture of 6-(6-bromo-1H-benzo [d] imidazol-1-yl)nicotinic acid amide and 6-(5-bromo-1H-benzo [d] imidazol-1-yl)nicotinic acid amide as positional isomers in a ratio of 1:1, prepared from 5-bromo-1H-benzo[d]imidazole and 6-chloronicotinic acid amide by the same method as in Production Example 105, and 0.36 g 3-[4-(methylsulfanyl)phenyl]-1-trityl-1H-4-pyrazolylboronic acid (compound in Production Example 26), were reacted in the same manner as in Example 29, to give 0.39 g brown amorphous as a mixture of 6-(6-{3-[4-(methylsulfanyl)phenyl]-1-trityl-1H-4-pyrazolyl}-1H-benzo[d]imidazol-1-yl)nicotinamide and 6-(5-{3-[4-(methylsulfanyl)phenyl]-1-trityl-1H-4-pyrazolyl}-1H-benzo [d]imidazol-1-yl)nicotinamide. This product was dissolved in 10 mL tetrahydrofuran and 5 mL methanol, then a solution of 0.17 g oxone in 3 mL water was added thereto, and the mixture was stirred at room temperature for 2 hours. Water and an aqueous sodium thiosulfate solution were added thereto, the reaction solution was stirred for 0.5 hour and extracted with ethyl acetate, and the organic layer was washed with brine and dried over sodium sulfate. The solvent was evaporated, and then the residue was purified by NAM silica gel chromatography (dichloromethane/methanol) to separate the positional isomer to give 0.14 g 6-(6-{3-[4-(methylsulfinyl)phenyl]-1-trityl-1H-4-pyrazolyl}-1H-benzo[d]imidazol-1-yl)nicotinamide as a colorless amorphous. This product was dissolved in 6 mL tetrahydrofuran and 3 mL methanol, then a solution of 0.13 g oxone in 2 mL water was added thereto, and the mixture was stirred at room temperature for 2 hours. Water and an aqueous sodium thiosulfate solution were added thereto, the reaction solution was stirred for 0.5 hour and extracted with ethyl acetate, and the organic layer was washed with brine and dried over sodium sulfate. The solvent was removed, whereby 0.15 g 6-(6-{3-[4-(methylsulfonyl)phenyl]-1-trityl-1H-4-pyrazolyl}-1H-benzo-[d]imidazol-1-yl)nicotinamide was obtained as a colorless amorphous. This product was subjected to deprotection of the trityl group and converted into the corresponding hydrochloride by the same method as in Example 67, to give 62 mg of the title compound as colorless crystals.

Provenance & Evidence