Lithium Hydroxide → 3-(3-(4-Fluoro-2-methoxyphenoxy)quinoxaline-2-carboxamido)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To ethyl 3-aminobenzoate (18.9 mg, 0.11 mmol) in DMF (0.3 mL) was added 3-(4-fluoro-2-methoxy-phenoxy)quinoxaline-2-carboxylic acid (30 mg, 0.09 mmol), HATU (54.4 mg, 0.14 mmol) and Et3N (39.9 μL, 0.29 mmol). The reaction is stirred at 50° C. for 2 hours. Lithium hydroxide (45 μL of 4M, 0.18 mmol) was added and the reaction was stirred at 25° C. overnight. The reaction was filtered and purified by reverse phase HPLC using a gradient of methanol in water (1-99%) and ammonium formate as a modifier to yield 3-(3-(4-fluoro-2-methoxyphenoxy)quinoxaline-2-carboxamido)benzoic acid (36) (16.4 mg, 42%). ESI-MS m/z calc. 433.11, found 434.0 (M+1)+; Retention time: 1.56 minutes (2.5 minutes run). 1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 8.39 (t, J=1.9 Hz, 1H), 8.18 (dd, J=8.0, 1.6 Hz, 1H), 7.99-7.92 (m, 1H), 7.87-7.68 (m, 4H), 7.48 (t, J=7.9 Hz, 1H), 7.35 (dd, J=8.8, 5.9 Hz, 1H), 7.16 (dd, J=10.7, 2.9 Hz, 1H), 6.88 (td, J=8.5, 2.9 Hz, 1H), 3.71 (s, 3H) ppm.

Provenance & Evidence