Benzyl Bromide → 5-Benzyl-2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Participants

Reaction Steps

To 452 mg (0.749 mmol) of 2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 38-(b) and 126 mg of potassium carbonate was added 4 ml of dehydrated N,N-dimethylformamide, then 0.1 ml of benzyl bromide was added to the mixture, and the resulting mixture was stirred at room temperature for 16 hours. Moreover, 36 mg of sodium hydride (55% dispersed material in mineral oil) and 0.1 ml of benzyl bromide were further added to the mixture, and the resulting mixture was stirred for 2 hours. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with toluene. The organic layer after separation was washed successively with water and then with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=19:1→1:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 389 mg of the title compound as a pale yellowish foam. (Yield: 75%)

Provenance & Evidence