Dimethylformamide → (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chloride

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Reaction Steps

To a cooled (ice-bath) suspension of 150 mg (0.63 mmol) of (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid in 15 mL of CH2Cl2 were added 0.081 mL (0.956 mmol) of oxalyl chloride, followed by a drop of DMF. The mixture was allowed to reach room temperature with stirring over two hours. Solvents were evaporated in in vacuo, and methylene chloride was added and solvent was removed in vacuo. Methynele chloride (10 mL) was again added and removed in vacuo, and the residue dried in high vacuum for 20 minutes to give (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chloride, which was dissolved in 8 mL of dry CH3CN and transferred to a sealable tube under Argon atmosphere. DIPEA 0.22 mL (1.26 mmol), DMAP (few crystals) were added, followed by 6-amino-5-ethylquinoline (60 mg 0.348 mmol). The tube was sealed and heated with stirring to 120° C. for 24 hours. The tube contents were cooled to room temperature, saturated aqueous NaHCO3 solution (10 mL) was added and product extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with CH2Cl2/MeOH/NH4OH (100/10/1) to give 30 mg (22.2%) of (S)-4-(4-Fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid (5-ethyl-quinolin-6-yl)-amide as a pale yellow foam. MS (ESI): m/z 389 (M+H)+.

Provenance & Evidence