Reacción #53519

Ecuación de reacción

2-Chloro-N-methylpyridinium iodide

(morpholine-4-carbothioyl)-carbamic acid ethyl ester

2-amino-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide bis hydrochloride salt

N,N-diisopropylethylamine

→

desired product

Rendimiento 26.0%

{[1-(4-Cyano-1-methyl-piperidin-4-ylcarbamoyl)-2-cyclohexyl-ethylamino]-morpholin-4-yl-methylen}-carbamic acid ethyl ester

Rendimiento 26.0%

Disolventes

citric acid

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with EtOAc
2. 2
   Extracciónextracted with EtOAc
3. 3
   ExtracciónThe organic extract
4. 4
   Secadowas dried (MgSO4)
5. 5
   Concentraciónconcentrated

Procedimiento

2-Chloro-N-methylpyridinium iodide (680 mg, 2.66 mmol), was added to a solution of (morpholine-4-carbothioyl)-carbamic acid ethyl ester (450 mg, 2.06 mmol), 2-amino-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide bis hydrochloride salt (745 mg, 2.04 mmol), and N,N-diisopropylethylamine (1.10 mL, 6.3 mmol) in dichloromethane (8.0 mL). The reaction was stirred at room temperature for 2.5 h then taken up in 10% citric acid solution and washed with EtOAc. The aqueous phase was then basified with saturated sodium carbonate and extracted with EtOAc. The organic extract was dried (MgSO4) and concentrated to provide the desired product as a white solid (250 mg, 26%). This material was further purified by HPLC using a 20×250 mm C18 reverse phase column with the method being 20% acetonitrile in water to 90% acetonitrile in water. MS, m/z 477=M+1.

Fuente