1-Pyrrolidineethanamine → 2-chloro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide

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Reaction Steps

To a stirred suspension of 2-hydroxyquinoline-4-carboxylic acid (preparation 10) (2.20 g, 12 mmol) in anhydrous DCM (60 ml), was added anhydrous DMF (36 drops) and thionyl chloride (3.3 ml, 46 mmol) under argon at room temperature. The mixture was refluxed for 3 h and then allowed to cool to room temperature. The solvents were removed under reduced pressure and the residue was dissolved in anhydrous THF (37 ml) under argon. 2-Pyrrolidin-1-ylethanamine (4.4 ml, 35 mmol) was added and the reaction was stirred at room temperature for 16 h. Solvents were removed under vacuum and the residue partitioned between NaHCO3 saturated aqueous solution (100 ml) and DCM (2×100 ml). The organic layers were combined, dried over MgSO4, filtrated and evaporated under reduced pressure. The crude was purified by column chromatography using a 24 g silica gel cartridge. Solvent A: DCM, Solvent B: 10% MeOH—NH3 in DCM. Gradient: 2 min hold 100% A followed by 18 min ramp to 40% B and then hold 5 min at 40% B. The desired fractions were combined and concentrated to dryness under reduced pressure to obtain the desired material as a white solid (2 g, 6.6 mmol, 56%).

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