4-Methylmorpholine → N-(1-(5'-chloro-3'-fluoro-3,5-dimethyl-2,4'-bipyridin-2'-yl)piperidin-4-yl)-3-(methylsulfonyl)propanamide

Participants

Reaction Steps

A stirred solution of 1-(5′-chloro-3′-fluoro-3,5-dimethyl-[2,4′-bipyridin]-2′-yl)piperidin-4-amine (81.5 mg, 0.20 mmol), 3-(methylsulfonyl)propanoic acid (45.7 mg. 0.30 mmol), and NMM (80.9 mg, 0.80 mmol) in DMF (2 mL) was treated with HATU (91.3 mg, 0.24 mmol) portionwise. The reaction solution was stirred at rt under nitrogen for 2 h. EtOAc (30 mL) and brine (10 mL) were added and layers were separated. The organic layer was washed with brine (2×), dried over sodium sulfate, and concentrated. Purification on ISCO separation system with a 4-gram column using 0-8% MeOH in EtOAc afforded a colorless gum, which was sonicated in heptane/EtOAc to furnish a solid. After solvent removal, 56 mg (60%) of waxy, white solid was obtained: LRMS (M+H)+: 469.1; 1H NMR (400 MHz, CDCl3) δ 1.52 (dd, J=12.51, 3.66 Hz, 2 H), 2.02 (d, J=12.38 Hz, 2 H), 2.15 (s, 3 H), 2.39 (s, 3 H), 2.74 (t, J=6.95 Hz, 2 H), 2.96 (s, 3 H), 2.97-3.12 (m, 2 H), 3.42 (t, J=7.07 Hz, 2 H), 3.89-4.12 (m, 3 H), 5.63 (d, J=7.33 Hz, 1H), 7.47 (d, J=0.76 Hz, 1 H), 8.10 (s, 1 H), 8.40 (d, J=1.26 Hz, 1 H).

Provenance & Evidence