Chloroacetyl chloride → 8-bromo-1-(chloromethyl)-6-(2-pyridyl)-4H-s triazolo[4,3-a][1,4]benzodiazepine

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Reaction Steps

15 g. of 7-bromo-5-(2-pyridyl)-3H-1,4-benzodiazepin-2-yl hydrazine (obtained as in Preparation 2) is slowly added to 150 ml. of acetic acid with external cooling. A solution of 6 g. of chloroacetyl chloride in 75 ml. of acetic acid is then added during about ten minutes, the solution is stirred at room temperature for about 1.5 hours and 4 g. of sodium acetate added with additional stirring for about 30 minutes, the mixture then being refluxed for about 3.25 hours. This mixture is cooled, poured into ice water and concentrated to a small volume, then diluted with water, neutralized with sodium bicarbonate and extracted with chloroform. The extract is dried over anhydrous magnesium sulfate, concentrated and the residue chromatographed on 1 kg. column of silica gel with 1% methanol -- 99% chloroform. The product obtained from the column is crystallized from ethyl acetate to give pure 8-bromo-1-(chloromethyl)-6-(2-pyridyl)-4H-s-triazolo-[4,3-a][1,4]benzodiazepine.

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