3-Methoxypropylamine → HCID 46908438, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-chloro-5-(5-(2-(methoxymethyl)-2′-methylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl)pyridin-2-ol (0.702 g; 1.72 mmol) and DIEA (0.24 mL; 1.38 mmol) in toluene (30 mL) was added phosphorus oxychloride (0.192 mL; 2.06 mmol). The reaction mixture was heated at 120° C. for 2 hours. The solvent was removed in vacuo and the residue tritutrated with MeCN to afford a solid. A portion of the solid (0.150 g) combined with 3-methoxypropylamine (0.039 mL; 0.39 mmol) and DIEA (0.104 mL; 0.60 mmol) in MeCN (2 mL). The reaction mixture was heated under reflux for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash chromatography on silica, eluting with iso-hexane/EtOAc (100% iso-hexane to 100% EtOAc) to afford the title compound as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 8.84 (1 H, d, J=2.0 Hz), 8.40 (1 H, d, J=1.7 Hz), 8.20 (1 H, d, J=2.0 Hz), 8.15 (1 H, dd, J=7.9, 1.9 Hz), 7.36-7.23 (4 H, m), 7.13 (1 H, d, J=7.4 Hz), 6.03 (1 H, t, J=5.2 Hz), 4.22 (2 H, d, J=2.1 Hz), 3.67 (2 H, q, J=6.0 Hz), 3.58 (2 H, t, J=5.67 Hz), 3.40 (3 H, s), 3.32 (3 H, s), 2.08 (3 H, s), 2.01-1.92 (2 H, m). LC/MS: 479 (M+H)+. HPLC (Method E) Rt 5.76 min (Purity: 99.8%).

Provenance & Evidence