Triethylamine → Ethyl 3-[1-(2-{3-Methoxy-4-[(2-toluidinocarbonyl)amino]phenyl}acetyl)-1,2,3,4-tetrahydro-6-quinolinyl]propanoate

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 3-methoxy-4-[3-(2-methylphenyl)ureido]phenylacetic acid (0.232 g, prepared as described in Example 52B of International Patent Application Publication No. WO 96/22966) in anhydrous tetrahydrofuran (5 ml), under an atmosphere of argon and at 20° C., was treated with powdered molecular sieves 4 Å (2 g), ethyl 3-(1,2,3,4-tetrahydro-6-quinolinyl)propanoate (0.115 g, Reference Example 2), triethylamine (0.275 ml), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.223 g) and 4-dimethylaminopyridine (6 mg). After stirring at 20° C. for 1 hour the reaction mixture was filtered through a pad of celite. The filtrate was evaporated under reduced pressure (2.7 kPa) at 40° C. and the residue was treated with ethyl acetate (25 ml). The solution obtained was washed twice with saturated aqueous ammonium chloride solution (5 ml), then with water (5 ml), then dried over magnesium sulfate, and then evaporated under reduced pressure (2.7 kPa) at 40° C. The resulting white foamy solid (0.457 g) was subjected to flash chromatography on silica (0,040-0,063 mm) eluting with a mixture of cyclohexane and ethyl acetate (250 ml, 9:1, then 500 ml, 7:3, then 1000 ml, 4:6; v/v) to give the title compound (0.244 g) as a white foamy solid.

Provenance & Evidence