Category: 118289-55-7

These common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Quality Control of 6-Chloro-5-(2-chloroethyl)indolin-2-one

Example 1: Preparation of ziprasidone base To de-ionized water (2.0 Lit), was added 5- (2-chloroethyl)-6-chloro-oxindole (100 g) and 1- (1, 2-benzisothiazol-3-yl) piperazine (210 g) at 30-35C. The mixture was slowly heated under stirring to 98-100C over 60-80 minutes. The resultant mass was stirred for 10-15 hours at 98-100C. After completion of reaction as monitored by HPLC, the suspended solid material was filtered at 98-100C. The wet cake so obtained was suspended in de-ionized water (2.0 Lit) and heated to 90-95C and maintained at this temperature for 30 minutes. The solid suspension was filtered at 90-95C. The wet cake was further added to isopropyl alcohol (1.5 Lit) and stirred for 2 hours at 30-35C. The solids were filtered and washed with isopropyl alcohol (500 ml) and dried under vacuum at 50-55C for 7-8 hours till moisture content was not more than 1.0% w/w.; Example 7: Preparation of ziprasidone base To de-ionized water (4.0 Lit), was added 5- (2-chloroethyl)-6-chloro-oxindole (200 g) and 1- (1, 2-benzisothiazol-3-yl) piperazine (419.8 g) at 30-35C. The mixture was slowly heated under stirring to 98-100C over 60-90 minutes. The resultant mass was stirred for 12-15 hours at 98-100C. After completion of reaction as monitored by HPLC, the suspended solid material was filtered at 98-100C. The wet cake so obtained was suspended in de-ionized water (4.0 Lit) and heated to 90-95C and further maintained at this temperature for 30 minutes. The solid suspension was filtered at 90-95C. The wet cake was further added to isopropyl alcohol (3.0 Lit) and the resultant mass was heated to reflux and maintained at reflux for 1 hour. The mass was further cooled to 30-35C and stirred for 1 hour at 30-35C. The solids were filtered and washed with isopropyl alcohol (1.0 Lit) and dried under vacuum at 50-55C for 10-12 hours till moisture content was not more than 1.0% w/w. The product so obtained was suspended in tetrahydrofuran (7.3 Lit) and de-ionized water (580 ml) and heated to reflux (65-67C). The resultant mass was maintained under reflux for 10-15 minutes at 65-67C and further stirred under reflux at 65-67C for 40-45 minutes to get a clear solution. Activated carbon (29 g) was added to the clear solution at 65-67C with stirring for 1 hour at 65-67C. The reaction mass was filtered while hot under vacuum through celite bed at 65-67C. The celite bed was washed with tetrahydrofuran (580 ml). The solvent was recovered under vacuum at 50-55C leaving behind about 2.2 Lit of the reaction mass. The resultant suspension was cooled under stirring slowly to 35C and maintained for further 30 minutes. It was further cooled to 3- 5C and maintained for 2 hours under stirring at 3-5C. The solid separated was filtered and the wet cake was slurry washed with isopropyl alcohol (870 ml). The product was then dried under vacuum at 50-55C for 7-8 hours till the moisture was less than 0.5 % w/w. Yield : 267 g (68%) Purity: 99.96% by HPLC Impurity : Single known or unknown impurity 0.03% by HPLC

The synthetic route of 6-Chloro-5-(2-chloroethyl)indolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RANBAXY LABORATORIES LIMITED; WO2005/85240; (2005); A2;,
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In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 118289-55-7 as follows. COA of Formula: C10H9Cl2NO

Example 1 6-chloro-5-(2-(4-(2,3-dihydrobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)indolin-2-one 6-chloro-5-(2-chloroethyl)indolin-2-one (120 mg, 0.52 mmol), the product of Reference Example 12 (115 mg, 0.52 mmol), potassium carbonate (215 mg, 1.56 mmol), potassium iodide (86 mg, 0.52 mmol) and acetonitrile (5 ml) were added to the flask and the mixture was stirred at 85 C. overnight. The reaction mixture was concentrated and subjected to column chromatography to obtain a white solid (120 mg, yield: 56%). 1HNMR (300 MHz, DMSO-d6): delta ppm 10.42 (brs, 1H), 7.21 (s, 1H), 7.07 (t, 1H), 6.90 (d, 1H), 6.80 (s, 1H), 6.69 (d, 1H), 3.45 (s, 2H), 3.30 (t, 2H), 3.14 (t, 2H), 2.74-2.95 (m, 6H), 2.59 (brs, 4H), 2.50 (t, 2H). ESI-MS (m/z): 414.2 [M+H]+.

According to the analysis of related databases, 118289-55-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES; SUZHOU VIGONVITA LIFE SCIENCES CO., LTD.; TOPHARMAN SHANDONG CO., LTD.; JIANG, Hualiang; WANG, Zhen; LI, Jianfeng; ZHANG, Rongxia; HE, Yang; LIU, Yongjian; BI, Minghao; LIU, Zheng; TIAN, Guanghui; CHEN, Weiming; YANG, Feipu; WU, Chunhui; WANG, Yu; JIANG, Xiangrui; YIN, Jingjing; WANG, Guan; SHEN, Jingshan; (70 pag.)US2017/158680; (2017); A1;,
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Related Products of 118289-55-7, These common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Charged 5-(2-Chloro ethyl)-6-chloro oxindole (50 gm), 3-(1-piperazinyl)-1,2-benzisothiazole (47.5 gm) and cyclohexane (500 ml) in to autoclave. To this sodium carbonate (46 gm), sodium iodide (3.2 gm), tetra butyl phosphonium bromide (14.8 gm) was added and maintained the reaction at temperature 95-102 C. and the pressure was 2.5 kg/cm2 till the reaction complete. The reaction mass was cooled to 30 C. and added water (250 ml), filtered the compound, washed with water (100 ml). The wet compound was further slurred in water (500 ml), filtered and washed with water (100 ml). To the water wet compound added acetone (500 ml) and stirred at room temperature for 2 hours and 30 minutes. The solid was filtered, washed with acetone (100 ml) and dried at a temperature of 60-65 C. to afford the Ziprasidone base (65.7 gm)

The synthetic route of 118289-55-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DR. REDDY’S LABORATORIES LIMITED; DR. REDDY’S LABORATORIES, INC.; US2005/49295; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Quality Control of 6-Chloro-5-(2-chloroethyl)indolin-2-one

i. Synthesis of 5- [2- [4- (1, 2- benzisothiazol-3-yl) -1-piperazinyl] ethyl] -6-chloro-1, 3-dihydro-2H-indol-2-one (Ziprasidone base) An amount of 5.00 g (0.023 mol) of 3-(1-piperazinyl)1,2-benzisothiazole, 5.77 g (0.025 mol) of 6-Chloro-5-(2-Chloroethyl)-1,3-Dihydro-2H-Indol-2-One, 2.44 g (0.023 mol) of Na2CO3 and 37.5 ml of 1-ethyl-3-methylimidazolium ethylsulfate were mixed to obtain homogenous suspension. The suspension was heated to about 100 C and maintained at the same temperature until the end of reaction. The reaction mixture was then cooled to room temperature and precipitated with 50 ml of MeOH, mixed for 1 hour and filtrated. Finally, 10 g of product containing 97.6 area % (by HPLC) of Ziprasidone base were obtained. ii. Synthesis of 5- [2- [4- (1, 2- benzisothiazol-3-yl) -1-piperazinyl] ethyl] -6-chloro-1, 3-dihydro-2H-indol-2-one (Ziprasidone base) Example 13.i. was repeated with the exception that 50 ml of 2-propanol were used instead of methanol for precipitation. 10.1 g of wet product containing 97.6 area % (by HPLC) of Ziprasidone base was obtained.; iii. Synthesis of 5- [2- [4- (1, 2- benzisothiazol-3-yl) -1-piperazinyll ethyl] -6-chloro-1, 3-dihydro-2H-indol-2-one (Ziprasidone base) Filtrate (mixture of ionic liquid and methanol) as obtained according to Example 13.i. was reused for reaction in such way that methanol was evaporated. Example 13.i. was repeated with the exception that reused 1-ethyl-3-methylimidazolium ethylsulfate was added. Purity of the obtained product was > 90 area % (by HPLC).

The synthetic route of 118289-55-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KRKA; EP1889844; (2008); A2;,
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Indoline | C8H9N – PubChem

Electric Literature of 118289-55-7, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 1; 5- (2- (4- (1, 2-benzisotliiazol-3-yl)-l-piperazitiyl) ethyl)-6-chloro-1, 3-diliydro-2H-indole-2-one (Ziprasidone); In a 10 liter three-necked round bottom flask sodium carbonate (742 g) and pure water (3.06 liter) is charged. To the above stirred solution 1, 2-benzisothiazole-3-piperazinyl HCl (611 g, 2 moles) is added at ambient temperature and stirred the reaction mixture additionally for 1 hour. To the obtained suspension 2-Chloroethyl-6-chloro oxindole (430 g, 2 moles) and sodium iodide (20 g) is added. The combined reaction mixture is heated at 60 to 90 C for 20 to 30 hours. After completion of the reaction, reaction mass is cooled to ambient temperature and the slurry thus obtained is stirred for 1 hour more and then filtered. The wet tan colored crude free base is suspended in water (7.50 liter), heated to 75 to 80 C under stirring for 1 hour and filtered at 45 to 50 C temperature. Wet compound is dried at 65 to 70 C for 10 to 12 hours to get desired product in 752 gm yield (HPLC Purity 95 to 96%).

The synthetic route of 6-Chloro-5-(2-chloroethyl)indolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; WOCKHARDT LIMITED; JAWEED MUKARRAM, Siddiqui, Mohammed; MERWADE, Aravind, Yekanathsa; SINGH, Kumar, Kamlesh, Laxmi; SOLANKI, Pawan, Vrajlal; WO2005/54235; (2005); A1;,
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118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. HPLC of Formula: C10H9Cl2NO

2 moles of Piperazine Benzisothiazole , 1 mole of 5-(2-chloroethyl)-6- chlorooxindole in water (20 times based on benzisothiazole) and in the presence of dispersing agent. All the reactants are charged in to the flask and refluxed under nitrogen, -under stirring ^or^ r2-i6hr. After the completion “of the reaction,” the” reaction mass is cooled to room temperature and the resulting mass is filtered. It is slurried inwater and then in IPA and isolated by filtration. The solid is dried at 95- 1000C.Yield: 92%, Purity 99 %( min).

The synthetic route of 118289-55-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ALKEM LABORATORIES LTD.; WO2009/116085; (2009); A2;,
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Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, A new synthetic method of this compound is introduced below., HPLC of Formula: C10H9Cl2NO

Refluxed the reaction mixture of 5- (2-chloroethyl)-6-chloro oxindole (100 GM), 3- (1-piperazinyl)-1, 2-benzisothiazole (104.7 gm), sodium carbonate (92.2 gm), sodium iodide (6.4 gm), tetra butyl ammonium bromide (28 gm) and cyclohexane (1000 mL) till the reaction was completed. The reaction mass was cooled to a temperature of 30C and the solid was filtered. To the wet compound was added water (1000 mL) and continued stirring for 45 minutes. The solid was filtered and washed with water (100 mL). To the water wet compound was added acetone (500 mL) and there was stirring for 2 hours at room temperature. The compound was filtered and washed with acetone (200 mL) and dried at a TEMPERATURE OF70-75C to afford the CRUDE Ziprasidone base (156.9 g)

The synthetic route of 118289-55-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DR. REDDY’S LABORATORIES LIMITED; DR. REDDY’S LABORATORIES INC.; WO2004/50655; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 118289-55-7, These common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Refluxed the reaction mixture of 5-(2-Chloro ethyl)-6-chloro oxindole (100 gm), 3-(1-piperazinyl)-1,2-benzisothiazole (104.7 gm), sodium carbonate (92.2 gm), sodium iodide (6.4 gm), tetra butyl ammonium bromide (28 gm) and cyclohexane (1000 ml) till the reaction completes. The reaction mass was cooled to a temperature of 30 C. and filtered the solid. To the wet compound added was water (1000 ml) and continued stirring for 45 minutes. The solid was filtered and washed with water (100 ml). To the water wet compound added acetone (500 ml) and stirred for 2 hours at room temperature. Filtered the compound and washed with acetone (200 ml) and dried at a temperature of 70-75 C. to afford the Crude Ziprasidone base (156.9 gm)

Statistics shows that 6-Chloro-5-(2-chloroethyl)indolin-2-one is playing an increasingly important role. we look forward to future research findings about 118289-55-7.

Reference:
Patent; DR. REDDY’S LABORATORIES LIMITED; DR. REDDY’S LABORATORIES, INC.; US2005/49295; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 118289-55-7,Some common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, molecular formula is C10H9Cl2NO, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a flask equipped with mechanical stirrer, thermometer, condenser and nitrogen inlet was added 6-chloro-5-(2-chloroethyl)-l,3-dihydro-2H-indol-2- one (21.6 g, 94 mmol), 3-(l-piperazinyl)-l,2-benzoisothiazole hydrochloride (24 g, 94 mmol), sodium carbonate (29.9 g, 282 mmol) and l-methyl-2- pyrrolidinone (NMP) (96 ml) and the mixture was heated to 130-1350C under nitrogen for about 24 hrs. The mixture was cooled to 40-450C and poured into water. The suspension was cooled and the product was collected by filtration on a Buchner funnel, the filter cake was rinsed with water at 20- 250C and the damp product was transferred to a drying oven and dried in vacuo. This afforded 34.2 g (88.2% yield) of crude ziprasidone. The IR (KBr) and NMR spectra were consistent with those of reference ziprasidone.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Chloro-5-(2-chloroethyl)indolin-2-one, its application will become more common.

Reference:
Patent; APOTEX PHARMACHEM INC.; WO2006/47893; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 118289-55-7 as follows. HPLC of Formula: C10H9Cl2NO

General procedure: Equimolar mixture of 6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one 1 (1.00mol) and the carbonyl compound (4i-x) (1.00mol) was stirred at RT in methanol (10mL) for 2h in presence of potassium carbonate (1.20mol). After completion, the reaction mass was filtered to remove inorganic salt, added methanol (10-20mL) and activated charcoal to the filtrate and stirred for 1hr. The crude product was filtered to remove charcoal, methanol was evaporated and cooled to 0-5C to get crude solid. Recrystallized using aqueous ethanol or methanol (Yield 60-70%).

According to the analysis of related databases, 118289-55-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Meti, Gangadhar Y.; Kamble, Atulkumar A.; Kamble, Ravindra R.; Somagond, Shilpa M.; Devarajegowda; Kumari, Sandhya; Kalthur, Guruprasad; Adiga, Satish K.; European Journal of Medicinal Chemistry; vol. 121; (2016); p. 221 – 231;,
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Indoline | C8H9N – PubChem