Triethylamine → 1-[[4-[8-Chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]-1-(2,2-dimethylnon-8-enoyl)pyrrolidine-2-carbonyl]amino]-2-vinylcyclopropanecarboxylic acid ethyl ester

Participants

Reaction Steps

To a solution of 2,2-dimethylnon-8-enoic acid (52, 239 mg, 1.3 mmol) in dry CH2Cl2 (10 mL) was added oxalyl chloride (165 mg, 2.6 mmol) and 2 drops of DMF. After 3 h at room temperature, the reaction mixture was concentrated and co-evaporated with toluene. This crude acid chloride was successively re-dissolved in CH2Cl2 and added to a stirred solution of 1-[[4-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]pyrrolidine-2-carbonyl]amino]-2-vinylcyclopropanecarboxylic acid ethyl ester (50, 380 mg, 0.65 mmol) and triethylamine (264 μL, 1.95 mmol) in CH2Cl2 (30 mL). After 1.5 h, the resulting solution was successively washed with a saturated solution of NaHCO3 and brine, dried (MgSO4), filtered and concentrated under reduced pressure. Purification by flash chromatography (gradient EtOAc/CH2Cl2 0:1 to 2:8) afforded the title product (53) as a colorless oil (490 mg, 100%): m/z=751 (M+H)+.

Provenance & Evidence