4-Methylmorpholine → Pavinetant

Participants

Reaction Steps

A solution of 3-[(methylsulfonyl)amino]-2-phenylquinoline-4-carboxylic acid (1c) (342 mg, 1.0 mmol), HOBT hydrate (231 mg, 1.5 mmol), 4-methylmorpholine (276 μL, 1.5 mmol) in tetrahydrofuran (50 ml) was added EDCI (289 mg, 1.5 mmol) at RT under N2. (S)-1-Phenyl propylamine (135 mg, 1.0 mmol) was then added and the reaction mixture stirred at RT for 12 h. All solvent was removed in vacuo and the residue was partitioned between ethyl acetate and 10% aqueous sodium bicarbonate solution, dried over sodium sulfate and then concentrated in vacuo. The residue was purified by chromatography eluting with 15-25% ethyl acetate/hexane to give the title compound (70 mg, 15%) as a solid. 1H NMR (300 MHz, CDCl3) δ 0.94 (t, 3H), 1.97 (m, 2H), 3.44 (s, 3H), 5.17 (q, 1H), 5.47 (m, 2H), 7.32 (d, 2H), 7.34 (d, 2H), 7.39 (m, 1H), 7.78 (m, 2H), 7.84 (m, 2H), 8.08 (m, 1H), 8.30 (m, 2H), 8.42 (m, 2H). MS APCI, m/z=460 (M+1). LCMS: 2.51 min.

Provenance & Evidence