Triethylamine → HCID 131728657, compound

Participants

Reaction Steps

(3-{4-[(6-Butyl-8-quinolinyl)oxy]-1-piperidinyl}propyl)amine (for example, as prepared for Intermediate 36) (30 mg, 0.09 mmol) was dissolved in DCM (1 ml), and treated with triethylamine (38 μl, 0.27 mmol), and 2-propanesulfonyl chloride (commercially available, for example, from Aldrich) (20 μl, 0.18 mmol). The mixture was stirred in a stoppered vial at room temperature for 1 h, then left to stand at room temperature overnight. LCMS analysis indicated that reaction was not complete. Further triethylamine (38 μl, 0.27 mmol), and 2-propanesulfonyl chloride (17 μl, 0.18 mmol) were added and the mixture stirred at room temperature for 1.5 h. LCMS analysis indicated that reaction was still not complete. Further triethylamine (19 μl, 0.14 mmol), and 2-propanesulfonyl chloride (10 μl, 0.09 mmol) were added and the mixture stirred at room temperature overnight. The mixture was diluted with methanol and applied to an SCX-2 cartridge (5 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 an impurity, 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: LCMS RT=2.68 min, ES+ve m/z 448 (M+H)+. The material was dissolved in methanol and treated with 1.25 M hydrogen chloride in methanol (0.5 ml, excess). The volatiles were removed under a stream of nitrogen to give the title compound (13 mg, 27%): LCMS RT=2.80 min, ES+ve m/z 448 (M+H)+.

Provenance & Evidence