Triethylamine → 7-Chloro-4-[[4-[[[1-(phenylmethyl)-4piperidinyl]amino]carbonyl]phenyl]amino]-3-quinolinecarboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

4-[(4-Carboxyphenyl)amino]-7-chloro-3-quinolinecarboxylic acid ethyl ester hydrochloride (40.0 g, 98.2 mmol), 1-hydroxybenzotriazole hydrate (16.2 g, 120 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (24.5 g, 128 mmol) were stirred in 560 ml of DMF and treated with triethylamine (39.8 g, 54.8 ml, 393 mmol) followed by 4-amino-1-benzylpiperidine (20.6 g, 22.0 ml, 108 mmol). The reaction mixture was heated at 85° C. for 3.5 h, poured into 1.3 L of CH2Cl2 and washed with 3×500 ml of water. The organic phase was dried over Na2SO4 and concentrated in vacuo for 3 days. This afforded 51.7 g (95.2 mmol, 97% yield) of 7 -chloro-4-[[4 -[[[1-(phenylmethyl)-4-piperidinyl]amino]carbonyl]phenyl]amino]-3-quinolinecarboxylic acid ethyl ester as a yellow solid.

Provenance & Evidence