53786-45-1

Ethyl 4-((2-Amino-4-chlorophenyl)amino)piperidine-1-carboxylate is an impurity of Domperidone(D531100); a novel peripheral dopamine receptor antagonist that does not cross the blood-brain barrier; anti-emetic. Domperidone(Motilium) is a dopamine blocker and an antidopaminergic reagent.

2. 1.34 kg of the crude product (domperidone impurity 7) obtained in the first step was dissolved in a solvent mixture of 15 L of methanol and 15 L of tetrahydrofuran with 1.3 L of water. Subsequently, zinc powder and 1.1 kg of ammonium chloride were added and the reaction was carried out at 25 °C for 5 hours. After completion of the reaction, the zinc powder was removed by filtration. Methanol and tetrahydrofuran were recovered by concentration under reduced pressure. The residue was dissolved in 15 L of ethyl acetate and the organic phase was washed with 15 L of water. The organic phase was recrystallized by adding 1 kg of ethyl acetate and 3 kg of petroleum ether to give 1.06 kg of an off-white solid, domperidone intermediate (DP-2), with 99% purity and 88% yield.

[1] Journal of Medicinal Chemistry, 1987, vol. 30, # 5, p. 814 - 820
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 19, p. 5052 - 5056
[3] Patent: US4470989, 1984, A
[4] Patent: CN108358832, 2018, A. Location in patent: Paragraph 0007; 0020; 0023; 0029; 0033; 0037