Diisopropylethylamine → 3-Amino-5-chloro-4-methyl-6-[(2-morpholin-4-yl-ethylcarbamoyl)-methoxy]-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

Participants

Reaction Steps

To a solution of (3-amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid (0.300 g, 0.843 mmol) in a 1:1 mixture of THF:DMF (2.0 ml each) are added 1-hydroxybenzotriazole hydrate (0.148 g, 1.096 mmol), N,N-diisopropylethylamine (0.163 g, 1.265 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.242 g, 1.265 mmol), and 4-(2-aminoethyl)morpholine (0.329 g, 2.529 mmol). The resulting solution is stirred at room temperature for 16 hours. The reaction is quenched by the addition of water (25 ml). If no precipitate forms, the mixture may be acidified to pH2 with 1 N HCl and extracted with EtOAc (25 ml). The organic layer is discarded and the aqueous layer is made basic (pH12) with 5N NaOH and extracted with EtOAc (40 ml). The organic layer is dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow solid. The solid is slurried in 3:1 hexane:EtOAc (10 ml), then filtered. The collected solid is dried in the vacuum oven at 50° C. for 72 hours. This affords the title compound as a yellow solid (0.053 g, 13%). Mass (m/z): 468.2 (M++1), 466.2 (M+−1).

Provenance & Evidence