7-Chloro-4-piperazinoquinoline

7-Chloro-4-piperazinoquinoline Property

Melting point:

113-116

Boiling point:

433.5±35.0 °C(Predicted)

Density 

1.257±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

Chloroform (Slightly), DMSO (Slightly), Methanol (Very Slightly)

form 

Solid

pka

8.62±0.50(Predicted)

color 

Light Yellow to Yellow

InChI

InChI=1S/C13H14ClN3/c14-10-1-2-11-12(9-10)16-4-3-13(11)17-7-5-15-6-8-17/h1-4,9,15H,5-8H2

InChIKey

DNXNPMDUDGUXOB-UHFFFAOYSA-N

SMILES

N1C2C(=CC=C(Cl)C=2)C(N2CCNCC2)=CC=1

Safety

Hazard Codes 

C,Xi,Xn

Risk Statements 

34-22

Safety Statements 

22-26-36/37/39-45

Hazard Note 

Corrosive

HazardClass 

IRRITANT

HS Code 

2933499090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H314Causes severe skin burns and eye damage

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P330+P331IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

7-Chloro-4-piperazinoquinoline Chemical Properties,Usage,Production

Uses

7-Chloro-4-(piperazin-1-yl)quinoline is a metabolite of Piperaquine phosphate (P480050), a low toxicity and quick acting antimalarial drug that is used to treat malaria.

Synthesis

4,7-Dichloroquinoline (2.00 g, 10.1 mmol), piperazine (4.35 g, 50.5 mmol, 5.0 eq.) and triethylamine (2.81 mL, 20.2 mmol, 2.0 eq.) were added to the reaction vial. The reaction vial was sealed under nitrogen protection and heated to 130 °C. Gradual dissolution of the solid was observed to form a clarified orange-yellow solution. A yellow precipitate appeared during the reaction. The progress of the reaction was monitored by thin layer chromatography (TLC) (unfolding agent: 5% v/v dichloromethane solution of methanol) and the reaction was completed after about 4 hours. The reaction mixture was cooled to room temperature and diluted with dichloromethane (25 mL) and water (25 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (3 x 25 mL). The organic phases were combined, washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a yellow solid crude product (2.60 g). The crude product was purified by silica gel column chromatography (eluent: dichloromethane/methanol, 100/0 to 98/2) to afford 7-chloro-4-(1-piperazinyl)quinoline (2.44 g, 9.85 mmol, 98% yield) as a yellow solid. The 1H NMR and 13C NMR data of the product were in agreement with literature reports.1H NMR (300 MHz, CDCl3): δ 8.71 (d, J = 4.9 Hz, 1H), 8.03 (d, J = 2.0 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.41 (dd, J = 2.0, 9.0 Hz, 1H), 6.82 (d, J = 2.0, 9.0 Hz, 1H), 7.41 (dd, J = 2.0, 9.0 Hz, 1H). 6.82 (d, J = 5.0 Hz, 1H), 3.17 (br s, 4H), 3.16 (br s, 4H); 13C NMR (75 MHz, CDCl3): δ 157.3, 151.9, 150.1, 134.7, 128.8, 126.0, 125.2, 121.9, 108.9, 53.5, 46.0; ESI-MS: m/z 248.

IC 50

Plasmodium

References

[1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5502 - 5505
[2] Indian Journal of Heterocyclic Chemistry, 2010, vol. 19, # 3, p. 215 - 220
[3] Journal of Medicinal Chemistry, 1998, vol. 41, # 22, p. 4360 - 4364
[4] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 10, p. 2882 - 2886
[5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 17, p. 4733 - 4736