Sodium Iodide → 6-Butyl-8-[(1-{3-[(1,1-di methylethyl)sulfonyl]propyl}-4-piperidinyl)oxy]quinoline, formate salt

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-butyl-8-(4-piperidinyloxy)quinoline (for example, as prepared for Intermediate 4) (28 mg, 0.10 mmol), sodium iodide (34 mg, 0.23 mmol) and sodium bicarbonate (60 mg, 0.7 mmol) was treated with a mixture of 3-bromopropyl 1,1-dimethylethyl sulfone and 3-chloropropyl 1,1-dimethylethyl sulfone (for example, as prepared for Intermediate 17) (1:1, 40 mg) in DMF (1.5 ml) and heated to at 150° C. for 15 min in a Smith Creator™ microwave oven. The reaction mixture was applied to an SCX-2 cartridge (10 g), preconditioned with methanol, and eluted with methanol, followed by 10% aqueous 0.88 s.g. ammonia in methanol. The ammoniacal fractions were combined and concentrated in vacuo and the residue was purified by MDAP to give the title compound (20 mg, 40%): LCMS RT=2.76 min, ES+ve m/z 447 (M+H)+; 1H NMR δ (CD3OD) 8.78 (1H, dd, J=4, 2 Hz), 8.44 (1.6H, s), 8.24 (1H, dd, J=8, 2 Hz), 7.52 (1H, dd, J=8, 4 Hz), 7.32 (1H, br s), 7.19 (1H, br s), 5.03-4.96 (1H, m), 3.68-3.59 (2H, m), 3.40-3.26 (4H, obscured by CD3OD), 3.22 (2H, t, J=7 Hz), 2.79 (2H, t, J=7 Hz), 2.35-2.21 (6H, m), 1.75-1.67 (2H, m), 1.45-1.35 (2H, m), 1.40 (9H, s), 0.96 (3H, t, J=7 Hz).

Provenance & Evidence