DEHYDRO ARIPIPRAZOLE Chemical Properties

Melting point:

>139oC (dec.)

Boiling point:

654.4±55.0 °C(Predicted)

Density 

1.281±0.06 g/cm3(Predicted)

Flash point:

349℃

storage temp. 

2-8°C

solubility 

Chloroform (Slightly), Methanol (Slightly, Heated)

form 

Solid

pka

11.22±0.70(Predicted)

color 

White to Off-White

InChIKey

CDONPRYEWWPREK-UHFFFAOYSA-N

Safety Information

Hazard Codes 

F,T

Risk Statements 

11-23/24/25-39/23/24/25-52/53

Safety Statements 

16-36/37-45-61

RIDADR 

UN 3286 8(6.1)(3) / PGII

WGK Germany 

1

HS Code 

2933790002

DEHYDRO ARIPIPRAZOLE Usage And Synthesis

Uses

Dehydro Aripiprazole (Aripiprazole EP Impurity E; Aripiprazole USP Related Compound G) is an impurity of Aripiprazole (A771000), a selective dopamine D2-receptor antagonist with dopamine autoreceptor agonist activity.

General Description

Dehydro Aripiprazole is the primary, active metabolite of aripiprazole, marketed as the atypical antipsychotic Abilify^? for the treatment of schizophrenia, bipolar disorder, and clinical depression. This new certified solution standard is suitable for use in LC or GC applications including forensic or clinical toxicology analysis and urine drug testing.

Synthesis

The general procedure for the synthesis of 7-[4-[4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy]-3,4-dihydroquinolin-2(1H)-ones from 7-(4-(4-(4-(2,3-dichlorophenyl)-1-piperazinyl)butoxy)-2(1H)-quinolinone was as follows: Example 1: Large-scale synthesis of dehydroaripiprazole [7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)quinolin-2(1H)-one] (Compound 1; Formula VI) Aripiprazole (Formula VIA) 1. 15 g (0.03 mol) of 7-(4-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one was dissolved in 360 mL of anhydrous tetrahydrofuran to form a clarified solution. 2. 12 mL (0.16 mol) of trifluoroacetic acid was added to the solution. 3. 24.3 g (0.11 mol) of 1,2-dichloro-4,5-dicyanoquinone was added and the mixture was stirred at room temperature under a nitrogen atmosphere. 4. After the reaction was stirred for 40 minutes, TLC assay showed complete consumption of the raw material. 5. 1.5 L of water was added and then the reaction mixture was alkalized to pH 12 with 50% NaOH aqueous solution. 6. The reaction mixture was extracted with dichloromethane (3 x 300 mL), the organic phases were combined and dried with MgSO4. 7. The crude product was purified by column chromatography using silica as stationary phase and dichloromethane to 10% methanol/dichloromethane as eluent. 8. The product was purified by 2-propanolysis. 8. The product was further purified by recrystallization from 2-propanol to give 13.7 g (92%) of off-white solid target product. Product characterization: 1H-NMR (400 MHz, CDCl3) δ 12.33 (1H, br s), 7.72 (1H, d), 7.42 (1H, d), 7.16-7.11 (2H, m), 6.98-6.93 (1H, dd), 6.83-6.79 (2H, m), 6.53 (1H, d), 4.10 (2H, t), 3.09 (4H, br), 4.10 (2H, t), 4.10 (2H, t). 3.09 (4H, br s), 2.67 (4H, br s), 2.52 (2H, t), 1.93-1.70 (4H, m). LCMS (acidic method) [M + H]+ 446.02, rt 14.246 min.

References

[1] Patent: US2011/275803, 2011, A1. Location in patent: Page/Page column 60-61
[2] Crystal Growth and Design, 2013, vol. 13, # 5, p. 2036 - 2046
[3] Heterocyclic Communications, 2005, vol. 11, # 6, p. 485 - 490

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