Trifluoroacetic acid → HCID 17984396, compound

Participants

Reaction Conditions

Reaction Steps

General Parallel Synthesis Procedure: 3-{3-Aminomethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid methyl ester: trifluoroacetic acid salt (565 mg, 1.1 mmol) was dissolved in CH2Cl2 (25 mL) and washed with saturated NaHCO3 solution (15 mL). The organic layer was dried (NaSO4), filtered, and concentrated to 3-{3-aminomethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid methyl ester (368 mg, 0.93 mmol, 84%). A portion of this free base (26 mg, 0.071 mmol) in CH2Cl2 (0.5 mL) was treated with triethylamine (0.075 mL, 0.54 mmol) then 2,5-dichloro-thiophene-3-carbonyl chloride (0.049 mL, 0.22 mmol). The reaction mixture was shaken overnight and dimethylethylenediamine (0.15 mL, 1.4 mmol) was added. The reaction mixture was shaken for 2 h and passed through an SCX column (1 g, equilibrated with 2 mL MeOH then 2 mL MeOH/CH2Cl2 1/1). The methyl ester-amide product was eluted with MeOH/CH2Cl2 (1:1, 10 mL) and concentrated. The residue was dissolved in THF (2 mL) and MeOH (2 mL) and treated with 5N NaOH (1 mL). The solution was heated at 55° C. for 2.5 h, cooled, and acidified with 5N HCl (1.5 mL). The mixture was transferred to a ChemElute cartridge and eluted with CH2Cl2. The solvent was removed under a stream of N2. The crude product was dried under vacuum and purified by mass-directed HPLC to give the title compound as a foam (9.9 mg, 26%).) MS (ESI) m/z 559.1 (M+H)+.

Provenance & Evidence