[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7](O)[CH:6]=[C:5]2[C:13]([OH:15])=O.CN(C=O)C.S(Cl)([Cl:23])=O.[N:25]1([CH2:30][CH2:31][NH2:32])[CH2:29][CH2:28][CH2:27][CH2:26]1>C(Cl)Cl>[Cl:23][C:7]1[CH:6]=[C:5]([C:13]([NH:32][CH2:31][CH2:30][N:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)=[O:15])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Cl:1])[CH:3]=2)[N:8]=1To a stirred suspension of 6-chloro-2-hydroxy-quinoline-4-carboxylic acid (preparation 8) (8.50 g, 38 mmol) in anhydrous DCM (250 ml), was added anhydrous DMF (2 ml) and thionyl chloride (11 ml, 152 mmol) at room temperature under argon. 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 (300 ml) under argon. 2-Pyrrolidin-1-ylethanamine (14 ml, 114 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 (250 ml) and DCM (2×250 ml). The organic layers were combined, dried over MgSO4, filtrated and evaporated under reduced pressure. The crude was purified by column chromatography using a 120 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 30% B and then 15 min hold at 30% B. The relevant fractions were combined and concentrated to dryness under reduced pressure to obtain the desired product as an off-white solid (5.6 g, 16.6 mmol, 43%).
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