847416-99-3

ML-213 is a selective KV7.2 (KCNQ2) and KV7.4 (KCNQ4) channel opener (EC50 values are 230 and 510 nM for KV7.2 and KV7.4 respectively). ML-213 displays >80-fold selectivity against KV7.1, KV7.3 and KV7.5 in a thallium-based fluorescence assay.

To a stirred suspension of cyclopent-2-en-1-one (2.50 g, 30.5 mmol) in dichloromethane (60 mL) was added tert-butyl carbamate (3.60 g, 30.5 mmol) and the reaction was stirred for 10-15 minutes. Subsequently, bismuth nitrate (14.70 g, 30.5 mmol) was added in batches and stirring was continued for about 5 hours at room temperature. After completion of the reaction, the reaction mixture was diluted with dichloromethane and filtered through a bed of diatomaceous earth. The filtrate was quenched with saturated sodium bicarbonate solution and the dichloromethane layer was separated. The aqueous layer was extracted with dichloromethane, the organic extracts were combined, dried with anhydrous sodium sulfate and concentrated to give the crude product. The crude product was purified by combiflash chromatography system using hexane solution of 10-15% ethyl acetate as eluent to give tert-butyl (3-oxocyclopentyl)carbamate as white solid (6.50 g, 36% yield). Mass spectrum (MS): 200.20 (M + H).

[1] Patent: WO2015/25197, 2015, A1. Location in patent: Paragraph 000136