Synthesis of Quinoline-4-Carboxylic Acid Derivative

Example 182

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6-(3-Fluoro-3-phenylazetidin-1-yl)quinoline-4-carboxylic acid Intermediate 343 (22 mg, 0.07 mmol), HATU (39 mg, 0.10 mmol) and DIPEA (48 μL, 0.27 mmol) were mixed in MeCN (1 mL) and EtOAc (1 mL). (R)-3-Glycylthiazolidine-4-carbonitrile hydrochloride Intermediate 4 (17 mg, 0.08 mmol) was added and the reaction mixture was stirred at rt for 1 h. DCM (8 mL) and NaHCO₃ (5 mL, aq) were added, and the reaction mixture was stirred, filtered through a phase separator and evaporated under reduced pressure. The crude compound was purified by preparative SFC, PrepMethod SFC-E, (gradient: 30-35%), to give the title compound (2.4 mg, 7%); HRMS (ESI) m/z [M+H]⁺ calcd for C₂₅H₂₃FN₅O₂S: 476.1550, found: 476.1560.