118289-55-7

Basic information

• Product Name: 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one
• Synonyms: 2H-INDOLE-2-ONE,5-CHLOROETHYL-6-CHLORO-1,3-DIHYDRO;5-CHLOROETHYL-6-CHLORO-1,3-DIHYDRO-1H-INDOL-2-ONE;5-CHLOROETHYL-6-CHLORO-1,3-DIHYDRO-2H-INDOLE-2-ONE;6-CHLORO-5-(2-CHLOROETHYL)-1,3-DIHYDRO-2H-INDOL-2-ONE;5-(2-CHLOROETHYL)-1,3-DIHYDRO-2H-6-CHLOROINDULE-2-ONE;2H-Indol-2-one-6-chloro-5-(2-chloroethyl)-1,3-dihydro;5-Chloroethyl-6-chloro-1,3-dihydro-2H-indol-2-one;6-Chloro-5-(2-Chloroethyl)-1,3
• CAS NO: 118289-55-7
• Molecular Formula: C₁₀H₉Cl₂NO
• Molecular Weight: 230.09
• EINECS: 421-320-0
• Product Categories: Indole;Indoles;(intermediate of ziprasidone hcl);Intermediates of Ziprasidone;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 118289-55-7.mol

Chemical Properties

• Melting Point: 218-221℃
• Boiling Point: 393.82 °C at 760 mmHg
• Flash Point: 191.976 °C
• Appearance: /
• Density: 1.376 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.592
• Storage Temp.: Refrigerator
• Solubility: soluble in Dimethylformamide
• PKA: 13.23±0.20(Predicted)
• CAS DataBase Reference: 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one(118289-55-7)
• EPA Substance Registry System: 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one(118289-55-7)

Safety Data

• Hazard Codes: N
• Statements: 50/53
• Safety Statements: 60-61-24/25
• RIDADR: 3077
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 118289-55-7(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one is used as a key intermediate in the synthesis of various organic compounds. Its unique structure allows for the creation of a wide range of molecules with diverse applications in different industries.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one is used as a building block for the development of new drugs. Its chemical properties make it a promising candidate for the creation of novel therapeutic agents, particularly in the areas of cancer treatment and other medical conditions.
Used in Chemical Research:
5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one is also utilized in chemical research to study the properties and behavior of similar compounds. This helps scientists understand the underlying mechanisms and interactions of these molecules, which can lead to the discovery of new applications and uses.

InChI:InChI=1/C10H9Cl2NO/c11-2-1-6-3-7-4-10(14)13-9(7)5-8(6)12/h3,5H,1-2,4H2,(H,13,14)

Synthetic route

6-chloro-5-(2-hydroxyethyl)-2-oxindole → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With triphenylphosphine In tetrahydrofuran; tetrachloromethane for 3h; Reflux;	97%

C17H16ClNO4S → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With lithium chloride In N,N-dimethyl-formamide at 50℃; for 8h;	95%

6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With triethylsilane; trifluoroacetic acid
Stage #1: 6-chloro-5-(2-chloroacetyl) indolin-2-one With triethylsilane; trifluoroacetic acid at 0 - 35℃; for 7h; Stage #2: With water at 5 - 10℃; for 1h;
With triethylsilane In trifluoroacetic acid at -5 - 45℃; for 7.5h;

6-chloro-2-oxindole (56341-37-8) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: AlCl3 / CS2 2: Et3SiH, CF3COOH View Scheme
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere 1.2: 35 - 37 °C / Inert atmosphere 2.1: trifluoroacetic acid / 0.25 h / 25 - 30 °C / Inert atmosphere 2.2: 0 - 35 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: aluminum (III) chloride / dichloromethane / 20 h / Reflux; Inert atmosphere 2: aluminum (III) chloride; 1,1,3,3-Tetramethyldisiloxane / dichloromethane / 0 °C / Inert atmosphere View Scheme

6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With triethylsilane; trifluoroacetic acid for 7h;
With aluminum (III) chloride; 1,1,3,3-Tetramethyldisiloxane In dichloromethane at 0℃; Inert atmosphere; chemoselective reaction;

6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Stage #1: 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one With trifluoroacetic acid at 20℃; for 1h; Stage #2: With triethylsilane at 35 - 40℃; for 13.5 - 15.5h;
Stage #1: 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one With trifluoroacetic acid at 20℃; for 1h; Stage #2: With triethylsilane at 35 - 40℃; for 13.5 - 15.5h;

2,5-dichloronitrobenzene (89-61-2) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: potassium carbonate / dimethyl sulfoxide / 25 - 30 °C / Inert atmosphere 1.2: 16 h / 40 - 85 °C 2.1: hydrogenchloride; tin / water; methanol / 10 - 70 °C 3.1: aluminum (III) chloride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere 3.2: 35 - 37 °C / Inert atmosphere 4.1: trifluoroacetic acid / 0.25 h / 25 - 30 °C / Inert atmosphere 4.2: 0 - 35 °C / Inert atmosphere View Scheme

dimethyl (4-chloro-2-nitrophenyl)malonate (147124-32-1) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride; tin / water; methanol / 10 - 70 °C 2.1: aluminum (III) chloride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere 2.2: 35 - 37 °C / Inert atmosphere 3.1: trifluoroacetic acid / 0.25 h / 25 - 30 °C / Inert atmosphere 3.2: 0 - 35 °C / Inert atmosphere View Scheme

6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 6-chloro-5-ethylindolin-2-one + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With triethylsilane; aluminum (III) chloride In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; Reflux;

6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 6-chloro-5-ethylindolin-2-one + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With aluminum (III) chloride; dimethylmonochlorosilane In dichloromethane at 0℃; Inert atmosphere; chemoselective reaction;

6-chloro-2-oxindole (56341-37-8) → 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 6-chloro-5-ethylindolin-2-one + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / dichloromethane / 20 h / Reflux; Inert atmosphere 2: aluminum (III) chloride; triethylsilane / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere; Reflux View Scheme

6-chloro-2-oxindole (56341-37-8) → 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / dichloromethane / 20 h / Reflux; Inert atmosphere 2: aluminum (III) chloride; 1,1,3,3-Tetramethyldisiloxane / dichloromethane / 0 °C / Inert atmosphere View Scheme

5-chloro-2,4-difluoronitrobenzene (1481-68-1) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: N,N-dimethyl-formamide / 12 h / 100 °C 2: hydrogenchloride; acetic acid / water / 18 h / Reflux 3: thionyl chloride / 4 h / 20 °C 4: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 5: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 6: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 7 steps 1: N,N-dimethyl-formamide / 12 h / 100 °C 2: hydrogenchloride; acetic acid / water / 18 h / Reflux 3: thionyl chloride / 4 h / 20 °C 4: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 5: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 6: triethylamine; dmap / dichloromethane / 5 h / Reflux 7: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

tetraethyl 4-chloro-6-nitro-1,3-benzenedimalonate → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: hydrogenchloride; acetic acid / water / 18 h / Reflux 2: thionyl chloride / 4 h / 20 °C 3: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 4: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 5: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 6 steps 1: hydrogenchloride; acetic acid / water / 18 h / Reflux 2: thionyl chloride / 4 h / 20 °C 3: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 4: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 5: triethylamine; dmap / dichloromethane / 5 h / Reflux 6: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

4-chloro-6-nitro-1,3-benzenediacetic acid → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / 4 h / 20 °C 2: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 3: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 4: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 5 steps 1: thionyl chloride / 4 h / 20 °C 2: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 3: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 4: triethylamine; dmap / dichloromethane / 5 h / Reflux 5: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

dimethyl 4-chloro-6-nitro-1,3-benzenediacetate → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 2: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 3: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 2: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 3: triethylamine; dmap / dichloromethane / 5 h / Reflux 4: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

methyl 6-chloro-(2-oxindol-5-yl)acetate → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 2: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 2: triethylamine; dmap / dichloromethane / 5 h / Reflux 3: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

2,4,5-Trichloronitrobenzene (89-69-0) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: potassium fluoride / N,N-dimethyl-formamide / 12 h / 125 °C / Inert atmosphere 2: N,N-dimethyl-formamide / 12 h / 100 °C 3: hydrogenchloride; acetic acid / water / 18 h / Reflux 4: thionyl chloride / 4 h / 20 °C 5: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 6: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 7: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 8 steps 1: potassium fluoride / N,N-dimethyl-formamide / 12 h / 125 °C / Inert atmosphere 2: N,N-dimethyl-formamide / 12 h / 100 °C 3: hydrogenchloride; acetic acid / water / 18 h / Reflux 4: thionyl chloride / 4 h / 20 °C 5: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 6: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 7: triethylamine; dmap / dichloromethane / 5 h / Reflux 8: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

3-(1-piperazinyl)-1,2-benzisothiazole (87691-87-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With Morwet D425 In water Reflux; Inert atmosphere;	92%
In water Inert atmosphere; Reflux; dispersing agent;	92%
With potassium carbonate; potassium iodide In sulfolane at 75 - 100℃; for 2h; Product distribution / selectivity;	75%

3-(1-piperazinyl)-1,2-benzoisothiazole hydrochloride + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With Morwet D425 In water Product distribution / selectivity; Reflux; Inert atmosphere;	92%
With sodium carbonate In water Product distribution / selectivity; Inert atmosphere; Reflux; Morwet D425;	90%
Stage #1: 3-(piperazin-1-yl)-1,2-benzisothiazole hydrochloride With potassium carbonate In acetonitrile for 0.5h; Stage #2: 6-chloro-5-(2-chloroethyl)-2-oxindole With sodium iodide In acetonitrile for 2h; Reflux;	767 g

6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) + 7-bromo-3-piperazinyl-1,2-benzisothiazole (155167-98-9) → 5-(2-(4-(7-bromo-1,2-benzisothiazol-3-yl)piperazinyl)-ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one (155167-99-0)

Conditions	Yield
With sodium carbonate In water at 115℃; for 20h;	89%

3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride (87691-88-1) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With sodium carbonate In 1-methyl-pyrrolidin-2-one at 130 - 135℃; for 24h; Product distribution / selectivity;	88.2%
With sodium carbonate In poly(ethylene glycol) methyl ether at 120 - 125℃; for 48h; Product distribution / selectivity;	88%
With sodium carbonate; sodium iodide In toluene for 22.5h; Product distribution / selectivity; Heating / reflux;	86%

4-(benzo[b]thiophen-4-yl)piperidine trifluoroacetate + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 5-(2-(4-(benzo[b]thiophen-4-yl)piperidin-1-yl)ethyl)-6-chloroindolin-2-one

Conditions	Yield
With potassium carbonate; potassium iodide In water at 105℃; for 12h;	58%

1-(2,3-dihydrobenzo[b]thiophen-4-yl)piperazine hydrochloride + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 6-chloro-5-(2-(4-(2,3-dihydrobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)indolin-2-one

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 85℃;	56%

1-(benzo[b]thiophen-4-yl)piperazine hydrochloride + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-6-chloroindolin-2-one hydrochloride

Conditions	Yield
With sodium carbonate; sodium iodide In water for 24h; Reflux;	51%

4-(piperazin-1-yl)thieno[2,3-c]pyridine trifluoroacetate + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 6-chloro-5-(2-(4-(thieno[2,3-c]pyridin-4-yl)piperazin-1-yl)ethyl)indolin-2-one

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 80℃;	8.7%

3-(1-piperazinyl)-1,2-benzisothiazole (87691-87-0) + acetone (67-64-1) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 5-[2-(4-1,2-benzisothiazol-3-yl-piperazin-1-yl)ethyl]-6-chloro-3-isopropylidene-1,3-dihydro-indol-2-one

Conditions	Yield
With potassium carbonate In water at 100℃; for 24h; Heating / reflux;	3%

6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 3-(1-piperazinyl)-1,2-benzisothiazole (87691-87-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) + 6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 5-(2-(4-(1,2-benzisothiazole-3-yl)-1-piperazinyl)-1-hydroxyethyl)-6-chloro-1,3-dihydro-2H-indole-2-one (884305-08-2) + 5-(2-(4-(1,2-benzisothiazole-3-yl)-1-piperazinyl)-1-oxoethyl)-6-chloro-1,3-dihydro-2H-indole-2-one (884305-07-1) + ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With tetrabutylammomium bromide; sodium carbonate; sodium iodide In cyclohexane Heating / reflux;

4-trimethylsilyl-1-(benzo[d]isothiazol-3-yl)piperazine + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With water; sodium carbonate; sodium iodide In N,N-dimethyl-formamide at 110℃; for 0.5h; Product distribution / selectivity;
With water; sodium carbonate; sodium iodide at 95 - 100℃; for 7.66667h; Product distribution / selectivity;

3-(1-piperazinyl)-1,2-benzisothiazole (87691-87-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprasidone hydrochloride

Conditions	Yield
Stage #1: 3-(1-piperazinyl)-1,2-benzisothiazole; 6-chloro-5-(2-chloroethyl)-2-oxindole With sodium carbonate; sodium iodide In water; dimethyl sulfoxide at 115 - 125℃; for 2.75h; Stage #2: With hydrogenchloride In water for 0.166667h;

1-(benzo[d]isoxazol-3-yl)piperazine hydrochloride (87691-90-5) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 5-(2-(4-(1,2-benziso-thiazol-3-yl)piperazinyl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one

Conditions	Yield
Stage #1: 1-(benzo[d]isoxazol-3-yl)piperazine hydrochloride With sodium carbonate In water at 20℃; for 1h; Stage #2: 6-chloro-5-(2-chloroethyl)-2-oxindole With sodium iodide In water at 20 - 90℃; for 21 - 31h; Stage #3: In water at 45 - 80℃; for 1h; Product distribution / selectivity;

Upstream product

• 118307-04-3 6-chloro-5-(2-chloroacetyl) indolin-2-one 
• 884305-06-0 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one 
• 89-69-0 2,4,5-Trichloronitrobenzene 
• 510703-85-2 6-chloro-5-(2-hydroxyethyl)-2-oxindole 
• 510703-84-1 methyl 6-chloro-(2-oxindol-5-yl)acetate 
• 510703-81-8 4-chloro-6-nitro-1,3-benzenediacetic acid 
• 1481-68-1 5-chloro-2,4-difluoronitrobenzene 
• 56341-37-8 6-chloro-2-oxindole 
• 147124-32-1 dimethyl (4-chloro-2-nitrophenyl)malonate 
• 89-61-2 2,5-dichloronitrobenzene 

Downstream Products

• 122883-93-6 ziprazidone 
• 884305-08-2 5-(2-(4-(1,2-benzisothiazole-3-yl)-1-piperazinyl)-1-hydroxyethyl)-6-chloro-1,3-dihydro-2H-indole-2-one 
• 884305-07-1 5-(2-(4-(1,2-benzisothiazole-3-yl)-1-piperazinyl)-1-oxoethyl)-6-chloro-1,3-dihydro-2H-indole-2-one 
• 684269-12-3 5-[2-(4-1,2-benzisothiazol-3-yl-piperazin-1-yl)ethyl]-6-chloro-3-isopropylidene-1,3-dihydro-indol-2-one 

Relevant articles and documents

Improved process for the preparation of 6-chloro-5-(2-chloroethyl)oxindole

The current process for ziprasidone involves preparation and isolation of the key intermediate 6-chloro-5-(2-chloroethyl)oxindole. An improved process for the synthesis of this intermediate is reported here. The new process involves use of a novel Lewis acid-mediated selective deoxygenation of the precursor ketone with tetramethyldisiloxane. The new method affords the desired compound in a one-pot process obviating the need for isolation of the potentially hazardous precursor ketone. This process was successfully scaled up to multikilo scale.

A SHORT PROCESS FOR THE PREPARATION OF ZIPRASIDONE AND INTERMEDIATES THEREOF

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 the preparation of ziprasidone

A process for the preparation of ziprasidone and a novel intermediate useful in its preparation. The process comprises the reduction of a compound (III) to give a compound (V) which is then reduced to compound (II). This is reacted with compound (IV) to give the desired compound.

A process for the preparation of ziprasidone

A process for the preparation of ziprasidone and a novel intermediate useful in its preparation. The process comprises the reduction of a compound (III) to give a compound (V) which is then reduced to compound (II). This is reacted with compound (IV) to give the desired compound.

Ziprasidone process

A process for preparing ziprasidone having low levels of keto ziprasidone and hydroxy ziprasidone impurities.

Process for the preparation of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1piperazinyl) ethyl)-6-chloro-1, 3-dihydro-2h-indol-2-one hydrochloride (ziprasidone hydrochloride) and its intermediate

The present invention relates to improved processes for the preparation of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl) ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one and its hydrochloride, which is known as Ziprasidone hydrochloride of Formula (I) and 5-(2-Chloro acetyl)-6-chloro oxindole of Formula (IV), which is an intermediate for the preparation of 5-(2-chloro ethyl)-6-chloro oxindole of Formula (V). Ziprasidone hydrochloride of Formula (I) of the present invention is depicted by the following structure.

POLYMORPHIC FORMS OF ZIPRASIDONE AND ITS HYDROCHLORIDE

The present invention is related to crystalline forms of ziprasidone and its hydrochloride salt and an amorphous form of ziprasidone hydrochloride and the process for the preparation thereof. The crystalline forms and amorphous form of the invention are suitable for pharmaceutical purposes in the treatment of psychosis. The processes of the invention are simple, non-hazardous and commercially suitable.

A PROCESS FOR THE PREPARATION OF OXINDOLE DERIVATIVES

A process for the preparation of oxindole derivative of formula (I) comprising reacting compound of formula (II) with dialkyl malonate, COOR1-COOR1, in the presence of a mild base to give compound of formula (III); and wherein R is selected from hydrogen, linear, branched or cyclic alkyl, aryl, substituted aryl, heteroaryl, haloalkyl like CF3, alkoxy, haloalkoxy, thioalkyl and halogen.; R1 is selected from linear, branched and cyclic alkyl (C1 to C4 groups); and X is selected from chloro, bromo, fluoro and iodo groups;further converting compound of formula (III) to compound of formula (I).

A new route to prepare 6-chloro-5-(2-chloroethyl)oxindole

6-Chloro-5-(2-chloroethyl)oxindole, a key intermediate in the manufacturing of the antipsychotic drug, ziprasidone, has been synthesized by a new route. The salient features of the synthesis are (1) bis-dialkylation of 2,4-difluoro-5-chloronitrobenzene with sodium diethyl malonate, (2) decarboxylative hydrolysis to obtain the oxindole derivative, and (3) reduction and chlorination of acetic ester side chain.

Method of treating psychiatric conditions

A method for treating a psychiatic condition or disorder selected from anxiety disorders such as panic disorder, posttraumatic stress disorder and phobias, psychotic episodes of anxiety, anxiety associated with psychosis, psychotic mood disorders such as severe major depressive disorder and mood disorders associated with psychotic disorders such as acute mania or depression associated with bipolar disorder, schizophrenia, behavioral manifestations of mental retardation, conduct disorder or autistic disorder, dementias such as dementias of the Alzheimer's type, and dyskinesias such as drug induced and neurodegeneration based dyskinesias in a mammal, including a human, comprising administering to said mammal a pharmaceutically effective amount of a compound of the formula or a pharmaceutically acceptable acid addition salt thereof, wherein n, X, Y and Ar are as defined above.