A solution of 5-chloro-pyridine-2-carboxylic acid (0.136 g, 0.86 mmol) in dichloromethane (15 ml), was treated with Huenig's base (0.30 ml, 1.73 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (0.328 g, 0.86 mmol) at room temperature. After 15 minutes of stirring, (RS)-5-(5-amino-2-fluoro-phenyl)-5-cyclopropyl-morpholine-3-thione (0.177 g, 0.66 mmol) was added and stirring continued for one hour. For the workup, the light yellow solution was poured on an ice-cold saturated solution of sodium hydrogen-carbonate, then extracted twice with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by chromatography on silica gel using a 9:1-mixture of dichloromethane and ethyl acetate as the eluent. The 5-Chloro-pyridine-2-carboxylic acid [3-((RS)-3-cyclopropyl-5-thioxo-morpholin-3-yl)-4-fluoro-phenyl]-amide was obtained as an off-white solid (0.245 g, 90% of theory). Mass (calculated) C19H17ClFN3O2S [405.879]; (found) [M+H]+=406.
