Diisopropylethylamine → 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid (2,2-diethoxyethyl)-amide

Participants

Reaction Steps

To a stirred solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid (prepared according to the methods described by Barth, et al. in U.S. Pat. No. 5,624,941); 740 mg, 2.01 mmol) and N-benzyl-N-(2,2-diethoxyethyl)amine (450 mg, 2.01 mmol) in methylene chloride (6.5 ml) at room temperature was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (464 mg, 2.42 mmol) and then diisopropylethylamine (0.42 ml, 2.2 mmol), dropwise. After stirring for 23 hours, the reaction mixture was concentrated, in vacuo, and then extracted from saturated aqueous sodium bicarbonate with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), and concentrated, in vacuo. The crude material (1.05 g) was purified on a Biotage™ Flash 40S column using 0-20% ethyl acetate in hexanes as eluant to afford I-1A-1a as a foam (534 mg, 46%): +ESI MS (M+1) 572.1; 1H NMR (500 MHz, CD2Cl2) 1:1 mixture of rotamers, δ 7.51 (br s, 0.5H), 7.47 (d, J=2.1 Hz, 0.5H), 7.38-7.34 (m, 2H), 7.38-7.23 (m, 9H), 7.18-7.11 (m, 2H), 7.03 (s, 0.5H), 6.95 (s, 0.5H), 5.22 (s, 1H), 4.91 (s, 1H), 4.83-4.79 (m, 1H), 3.56-3.07 (m, 6H), 1.20 (t, J=7.0 Hz, 3H), 1.07 (t, J=7.0 Hz, 3H).

Provenance & Evidence