Synthesis of Quinoline-Based Derivatives

Example 110

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To a vial were added (S)-2-((1-(7,8-dichloro-4-(1H-imidazol-1-yl)quinolin-2-yl)pyrrolidin-2-yl)methoxy)acetic acid (30 mg, 0.0712 mmol, 1.0 eq.), NH₄Cl (19 mg, 0.356 mmol, 5.0 eq.), EDC·HCl (27 mg, 0.142 mmol, 2.0 eq.), HOBt (9.6 mg, 0.0712 mmol, 1.0 eq), DMF (0.5 mL). With stirring, DIPEA (0.062 mL, 0.356 mmol, 5.0 eq.) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate (20 mL), washed with H₂O (3×10 mL), brine (10 mL), dried over Na₂SO₄. After concentration, the residue was purified by silica gel chromatography to afford the title product. MS: [M+1]⁺ 420.

The following compounds are prepared essentially by the same methods as described above for I-760.