122883-93-6 Usage
Description
Ziprasidone, marketed under the trade names Geodon and Zeldox, is an atypical antipsychotic medication. It is a potent 5-HT2A/D2 antagonist with a ratio of about 11 in favor of the serotonin receptor. Ziprasidone also exhibits high 5-HT2c antagonistic activity, high 5-HT1A agonistic, and 5-HT1D antagonistic activity, as well as moderate antagonism of α1 and H1 receptors and moderate norepinephrine and serotonin reuptake inhibition. Its complex binding profile for serotonin and dopamine receptors has led to high antipsychotic efficacy with low extrapyramidal side effects and antidepressive action with low propensity for weight gain compared to other atypical and typical neuroleptics. However, recent studies have suggested that Ziprasidone may increase the risk of Type II diabetes and hyperglycemia.
Uses
Used in Pharmaceutical Industry:
Ziprasidone is used as an atypical antipsychotic medication for the treatment of schizophrenia and bipolar disorder. Its complex binding profile for serotonin and dopamine receptors results in high antipsychotic efficacy with low extrapyramidal side effects and antidepressive action with low propensity for weight gain.
Used in Acute Agitation Treatment:
The intramuscular injection form of Ziprasidone is used for the treatment of acute agitation in patients with schizophrenia and agitated psychoses. An intramuscular formulation of ziprasidone has been demonstrated to be superior to haloperidol, a conventional neuroleptic, for the short-term treatment of agitation in acutely psychotic patients.
Used in Forensic Drug Analysis:
Ziprasidone is also used as a Certified Spiking Solution, applicable to use in forensic drug analysis or calibrator preparation by LC/MS or GC/MS.
Originator
Pfizer (US)
Manufacturing Process
Preparation of 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-
1,3-dihydro-2H-indol-2-oneA 20-gallon glass lined tank, under a nitrogen atmosphere, was charged with
33.5 liters of water and 9.4 kilograms (kg) of sodium carbonate (dense, 89.1
moles, 3.4 eq.). The resulting mixture was stirred to give a solution. To the
solution 6.4 kg of 2-chloroethyl-6-chloro-oxindole (27.8 moles, 1.06 eq.) was
charged, followed by 6.7 kg of 3-piperazinyl-1,2-benzisothiazole hydrochloride
(26.2 moles, 1.0 eq.). This was stirred and heated to reflux (100°C). After 11
hours the reaction was sampled for high pressure liquid chromatography
(HPLC) assay. The reflux was continued for another 2 hours then the reaction
was cooled to 25°C and the slurry stirred for 1 hour. The product was
observed and found to be essentially free from lumps and gummy matter. The
product was collected by filtration. A 14 liter water was added to the tank and
cooled to 12°C and then used to wash the product. The cake was pulled as
dry as possible, and the product was returned to the tank along with 40 liters
of isopropyl alcohol (IPO). This was cooled and then stirred for 2 hours and
the product was collected by filtration. The cake was washed with 13.4 liters
of fresh IPO, then dried under vacuum at 30° to 40°C. After drying, 17.3 kg
of the title compound was obtained. This was in excess of the theoretical
weight yield due to some residual carbonate in the crude product.Recrystallization of 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-
chloro-1,3-dihydro-2H-indol-2-oneTo a clean and dry 100-gallon glass lined tank was charged 9.0 kg of the
material obtained above and 86 gallons of tetrahydrofuran (THF). The slurry
was heated to reflux and held for 1 hour. The hazy solution was then filtered
through a 14" sparkler precoated with filter aid and backed with a Fulflo filter
to a clean, dry, and "spec free" glass-lined tank on a lower level. The batch
was concentrated by vacuum distillation. Another 8.3 kg of the material
obtained in above was dissolved in 83 gallons of THF in the upper tank. This
was filtered to the lower tank. The tank lines and sparkler were rinsed with 10
gallons of THF. The batch was concentrated to about 22 gallons, then cooled
to 5°C and stirred for 1 hour. The product was collected by filtration. Then 20
gallons of fresh IPO were cooled in the tank and used to rinse the product
cake. The product was collected and dried under vacuum at 45°C; yielding
9.05 kg of product (83.8% yield for the coupling and recrystallization. The
product matched the spectra of a standard NMR and showed the correct
retention time by HPLC with 99.7% assay. Another way for preparation of 5-(2-(4-(1,2-benzisothiazol-3-yl)-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2-H-
indol-2-one.A clean and dry 20-gallon glass lined tank was charged with 19 L of water and
4.44 kg of sodium carbonate, after the carbonate had dissolved 4.29 kg (17.5
moles) of 5-(2-chloroethyl)-6-chloro-oxindole and 3.62 kg (16.5 moles) of 1-
(1,2-benzisothiazol-3-yl)piperazine were added. The aqueous slurry was
heated to reflux and the temperature maintained for 14 hours. When the
reaction was complete the solution was cooled to 20°C and filtered. The wet
product was reslurried in 23 L of isopropyl alcohol at room temperature for 2
hours. The product was collected by filtration on 2 large Buchner funnels, each
was washed with 3.4 L of fresh isopropyl alcohol. The product was vacuum
dried at 30° to 40°C. until no isopropyl alcohol remained, giving 5.89 kg
(86.4% yield) of the desired free base which matched a standard sample by
high performance liquid chromatography (HPLC).A clean and dry 20-gallon reactor was charged with 17.4 gallons of deionized
water and 4.44 L of concentrated hydrochloric acid, to give a 0.77 M solution.
To the solution was added 4.44 kg of the anhydrous 5-(2-(4-(1,2-
benzisothiazol-yl)-1-piperazinyl)-ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one
free base. The slurry was warmed to 65°C and held for 18 hours. The slurry
was cooled to room temperature. The product was filtered and washed with
2x5-gallon portions of deionized water, and then air dried at 50°C for 30
hours. The dried product contained 4.4% water and the x-ray diffraction
method confirmed that the desired product was obtained.
Therapeutic Function
H-Indol-2-one, 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-
piperazinyl)ethyl)-6-chloro-1,3-dihydro-, monohydrochloride monohydrate
Check Digit Verification of cas no
The CAS Registry Mumber 122883-93-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,2,8,8 and 3 respectively; the second part has 2 digits, 9 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 122883-93:
(8*1)+(7*2)+(6*2)+(5*8)+(4*8)+(3*3)+(2*9)+(1*3)=136
136 % 10 = 6
So 122883-93-6 is a valid CAS Registry Number.
122883-93-6Relevant articles and documents
A key intermediate for the preparation of ziprasidone
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, (2018/04/03)
The present invention relates to a ziprasidone key intermediate preparation method, wherein benzo[d]isothiazole-3-ol (or one) is adopted as a raw material, and reacts with a substituted sulfonyl chloride or anhydride under an alkaline condition to obtain benzo[d]isothiazole-3-substituted sulfonate, and the benzo[d]isothiazole-3-substituted sulfonate reacts with piperazine to prepare the ziprasidone key intermediate 3-(1-piperazinyl)-1,2-benzoisothiazole. The method of the present invention has characteristics of simple operation, easily available raw materials, less byproducts, simple post-treatment, less industrial three-waste and the like, and is especially suitable for industrial production.
A SHORT PROCESS FOR THE PREPARATION OF ZIPRASIDONE AND INTERMEDIATES THEREOF
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Page/Page column 14-15, (2012/03/09)
A process for the preparation of oxindole derivative (Ziprasidone hydrochloride) of formula (I) comprising reacting compound of formula (II) with metal or metal compound mineral acid to give compound of formula (III) in a single step which is converted into compound of formula IV which is a key intermediate for the preparation of compound of compound of formula (I).
PROCESS FOR PURIFICATION OF ZIPRASIDONE
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Page/Page column 3-4, (2011/07/30)
The present invention relates to a process for the preparation of pure ziprasidone. Thus, for example, ziprasidone tosylate was added to water and aqueous ammonia at room temperature, the contents were heated to 65 °C and maintained for 30 minutes, filtered, washed with water to obtain a wet solid, tetrahydrofuran was added to wet solid and maintained at reflux for 30 minutes. The separated solid was filtered and dried at 65 °C to obtain pure ziprasidone.