Ammonium Chloride → Methyl 2-(5-(3-((4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)(methyl)carbamoyl)-5-(trifluoromethyl)phenylthio)pentanamido)acetate

Participants

Reaction Steps

To a solution of 5-(3-((4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)(methyl)carbamoyl)-5-(trifluoromethyl)phenylthio)pentanoic acid (0.15 g, 272 μmol, example 312) in DMF (1 mL) was added 1,1′-carbonyldiimidazole (66.3 mg, 409 μmol) and the clear solution was stirred at room temperature for 45 minutes before glycin methyl ester hydrochloride (37.6 mg, 300 μmol) was added. Reaction mixture was stirred at room temperature for 20.5 hours before DIPEA (35.2 mg, 47.6 μL, 272 μmol) and glycin methyl ester hydrochloride (37.6 mg, 300 μmol) was added. After 23 hours the reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed twice with water and once with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using a MPLC system eluting with a gradient of CH2Cl2:MeOHe (100:0 to 90:10). Colorless foam (0.142 g; 79%). MS (ESI): m/z=622.20 [M+H]+.

Provenance & Evidence