Diisopropylethylamine → 4-(2-{6-[4-(2-Hydroxy-2-methylpropylamino)-benzenesulfonyloxy]benzothiazol-2-ylcarbamoyl}ethyl)piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

A solution of 1-Boc-piperidin-4-ylpropionic acid (176 mg, 0.686 mmol), HBTU (260 mg, 0.686 mmol) and N,N-diisopropylethylamine (185 mg, 1.435 mmol) in 10 ml of dimethylformamide is stirred for 10 minutes. 4-(2-hydroxy-2-methylpropylamino)benzenesulfonic acid 2-aminobenzothiazol-6-yl ester; compound with trifluoroacetic acid (intermediate 82) (130 mg, 0.33 mmol) is added and the reaction medium is stirred for 48 hours at room temperature. Water is added to the reaction medium and the resulting mixture is then extracted 3 times with ethyl acetate. The organic phase is dried over magnesium sulfate and then concentrated to dryness. The dry residue is purified by reverse-phase chromatography on a 300×20 mm Dynamax C18 column, with a gradient over 5 minutes of 5% to 40% acetonitrile in water supplemented with 0.07% trifluoroacetic acid, and then from 40% to 80% over 30 minutes. The fractions containing the product are evaporated to dryness, to give 111 mg of 4-(2-{6-[4-(2-hydroxy-2-methylpropylamino)-benzenesulfonyloxy]benzothiazol-2-ylcarbamoyl}ethyl)piperidine-1-carboxylic acid tert-butyl ester in a yield of 51%.

Provenance & Evidence