Synthesis of Novel Quinoline-Thiazolidine Compound

Example 187

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6-(3-(4-Chlorobenzyl)azetidin-1-yl)quinoline-4-carboxylic acid Intermediate 353 (80 mg, 0.23 mmol), HATU (129 mg, 0.34 mmol) and DIPEA (158 μL, 0.91 mmol) were mixed in MeCN (2 mL) and EtOAc (2 mL). (R)-3-Glycylthiazolidine-4-carbonitrile hydrochloride Intermediate 4 (56 mg, 0.27 mmol) was added and the reaction mixture was stirred at rt for 3 h. DCM (15 mL) and NaHCO₃ (15 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 HPLC, PrepMethod F, (gradient 5-95%) to give the title compound (18 mg, 16%); HRMS (ESI) m/z [M+H]⁺ calcd for C₂₆H₂₅C₁N₅O₂S: 506.1412, found: 506.1428; ¹H NMR (600 MHz, DMSO-d₆) δ 8.89 (t, 1H), 8.57 (d, 1H), 7.82 (d, 1H), 7.36 (d, 1H), 7.33-7.29 (m, 2H), 7.25 (d, 2H), 7.11-7.03 (m, 2H), 5.27-5.21 (m, 1H), 4.82 (d, 1H), 4.66 (d, 1H), 4.24 (d, 2H), 3.99 (q, 2H), 3.66-3.59 (m, 2H), 3.35-3.28 (m, 2H), 2.99 (dt, 1H), 2.90 (d, 2H).