Triethylamine → HCID 131728658, compound

Participants

Reaction Steps

(4-{4-[(6-Butyl-8-quinolinyl)oxy]-1-piperidinyl}butyl)amine (for example, as prepared for Intermediate 37) (87 mg, 0.24 mmol) was dissolved in DCM (2 ml), and treated with triethylamine (167 μl, 1.2 mmol), and 2-propanesulfonyl chloride (commercially available, for example, from Aldrich) (54 μl, 0.48 mmol). The mixture was stirred at room temperature for 1.5 h. LCMS analysis indicated that reaction was not complete. Further triethylamine (167 μl, 1.2 mmol), and 2-propanesulfonyl chloride (54 μl, 0.48 mmol) were added and the mixture stirred at room temperature for 1 h. The reaction was quenched by the addition of methanol then concentrated under a stream of nitrogen. The residue was re-dissolved in methanol and applied to an SCX-2 cartridge (20 g) eluting with methanol, followed by 10% aqueous 0.88 s.g. ammonia in methanol. The relevant fractions were concentrated, and the residue was purified by MDAP. The appropriate fractions were combined and concentrated, but the product was found to contain impurities, thought to be (3-{4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinyl}propyl)sulfamic acid. The material was dissolved in methanol and applied to an aminopropyl cartridge (5 g) eluting with methanol. The relevant fractions were combined and concentrated to give the title compound as the free base (43 mg, 39%): LCMS RT=2.63 min, ES+ve m/z 462 (M+H)+. Approximately half the material was dissolved in methanol and treated with 1.25 M hydrogen chloride in methanol (1 ml, excess). The volatiles were removed under a stream of nitrogen to give the title compound (26 mg): LCMS RT=2.70 min, ES+ve m/z 462 (M+H)+.

Provenance & Evidence