Diisopropylethylamine → (RS)-5-chloro-pyridine-2-carboxylic acid [3-(3-cyclopropyl-5-thioxo-morpholin-3-yl)-4-fluoro-phenyl]-amide

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.

1. stirringstirring
2. waitcontinued for one hour
3. extractionextracted twice with dichloromethane
4. washThe combined organic layers were washed with brine
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customThe residue was purified by chromatography on silica gel using a 9

ORD record

ord-294e44bfe4b448af91331a05da2fd3b3

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188079B2