2-((2-((6-Bromohexyl)oxy)ethoxy)methyl)-1,3-dichlorobenzene → 6-{2-[(6-{2-[(2,6-Dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)pyridin-3-ol

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-amino-1-(2-phenyl-4H-[1,3]dioxino[5,4-b]pyridin-6-yl)ethanol (EP220054A2) (93 mg) and 2-({2-[(6-bromohexyl)oxy]ethoxy}methyl)-1,3-dichlorobenzene (98 mg) in dimethylformamide (1 ml) and diisopropylethylamine (0.2 ml) was heated to 70° C. for 4 h and then at 20° C. for 16 h. The mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic phase was washed with water, brine, dried and evaporated to dryness. The residue was dissolved in ethanol and applied to an SCX-2 cartridge (10 g) eluting with ethanol, followed by 10% aqueous ammonia in ethanol. The ammoniacal fractions were concentrated under reduced pressure, and the residue was dissolved in acetic acid (5 ml) and water (2 ml) and the mixture was heated to 70° C. for 40 min. The solvent was removed under reduced pressure and the residue was purified by chromatography on a silica SPE cartridge (10 g) eluting with 10% aqueous ammonia in ethanol-dichloromethane (1:9 to 1:3). Appropriate fractions were combined and concentrated and the residue dissolved in acetic acid and re-evaporated to dryness to give the title compound (124 mg). LCMS RT=2.46 min, ES+ve m/z 487/489/491 (M+H)+.

Provenance & Evidence