Methyl Glycolate → (3-Amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid methylester

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl glycolate (6.55 g, 72.7 mmol) in THF (35 ml) at room temperature is added dropwise a solution of lithium bis(trimethylsilyl)amide (1.0 M in hexanes) (36.35 ml, 36.35 mmol). The resulting mixture is stirred for 20 minutes, then treated with 3-amino-5-chloro-6-methanesulfinyl-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide (5.0 g, 14.54 mmol). The reaction vessel is sealed and heated at 90° C. for 3 hours. The reaction is cooled to room temperature and quenched by the addition of water (50 ml). The mixture is partitioned between water and EtOAc (250 ml each), and the layers are shaken and separated. The aqueous layer is extracted with 2×100 ml of EtOAc. The combined organic layers are dried (anhydrous magnesium sulfate), filtered, concentrated, and flashed (1:1 hexane:EtOAc) to give the title compound as a yellow solid (3.1 g, 58%). Mass (m/z): 370.1 (M++1), 368.0 (M+−1).

Provenance & Evidence