Diisopropylethylamine → Hydrochloric Acid

Participants

Reaction Steps

To a solution of 1.87 g (1.75 equiv.) 5-chloro-thiophene-2-carboxylic acid in 50 ml DMF were added 4.39 g (1.75 equiv.) HATU and 3.35 ml (3 equiv.) DIPEA. The resulting mixture was stirred for 30 min at room temperature. Subsequently a solution of 1.64 g (6.58 mmol) 2-amino-ethanesulfonic acid (1-isopropyl-piperidin-4-yl)-amide and 1.11 ml (1 equiv.) DIPEA in 20 ml DMF was added. The resulting mixture was stirred at room temperature overnight and concentrated under reduced pressure. The resulting residue was taken up in ethyl acetate and filtered. The filtrate was washed with a saturated NaHCO3-solution. Then, the product was extracted into the aqueous phase by treatment with a 0.1 N HCl-solution. Separation of the aqueous phase, then adjusting the pH to ≈9 by treatment with a saturated NaHCO3-solution and subsequent re-extraction with ethyl acetate brought the product back in the organic phase. Concentration under reduced pressure afforded crude 5-chloro-thiophene-2-carboxylic acid [2-(1-isopropyl-piperidin-4-ylsulfamoyl)-ethyl]-amide. Final purification was achieved by preparative RP-HPLC (CH3CN/H2O gradient+0.1% TFA). Lyophilisation and transformation into its hydrochloride gave the title compound as a colorless, amorphous solid. Yield: 1.76 g MS (ES+): m/e=394, chloro pattern.

Provenance & Evidence