ethyl 4-[(2-amino-4-chlorophenyl)amino]piperidine-1-carboxylate

Product Nameethyl 4-[(2-amino-4-chlorophenyl)amino]piperidine-1-carboxylate
CAS53786-45-1
MFC14H20ClN3O2
MW297.78
EINECS258-775-8
MOL File53786-45-1.mol

Chemical Properties

Boiling point	475.6±45.0 °C(Predicted)
Density	1.290±0.06 g/cm3(Predicted)
storage temp.	Keep in dark place,Inert atmosphere,Room temperature
pka	4.70±0.11(Predicted)
InChI	InChI=1S/C14H20ClN3O2/c1-2-20-14(19)18-7-5-11(6-8-18)17-13-4-3-10(15)9-12(13)16/h3-4,9,11,17H,2,5-8,16H2,1H3
InChIKey	PPCPQDDCMQRJLS-UHFFFAOYSA-N
SMILES	N1(C(OCC)=O)CCC(NC2=CC=C(Cl)C=C2N)CC1

Usage And Synthesis

Uses

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.

Synthesis

ethyl 4-[(4-chloro-2-nitrophenyl)amino]piperidine-1-carboxylate

53786-44-0

ethyl 4-[(2-amino-4-chlorophenyl)amino]piperidine-1-carboxylate

53786-45-1

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.

References

[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