Category: 18711-13-2

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 4,7-Dichloroindoline-2,3-dione

A. Synthesis of 4,7-dichloro-1-pentyl-1H-indole-2,3-dione To a mixture of sodium hydride (0.17 g, 6.94 mmol, 60% dispersion in mineral oil) in anhydrous N,N-dimethylformamide (5.00 mL) was added a solution of 4,7-dichloro-1H-indole-2,3-dione (1.00 g, 4.60 mmol) in N,N-dimethylformamide (5.00 mL) at 0 C. The brown reaction mixture was stirred for 0.5 h followed by the addition of a solution of 1-bromopentane (0.84 g, 5.55 mmol) in anhydrous N,N-dimethylformamide (5.00 mL). The reaction mixture was stirred at ambient temperature for 16 h and poured into wet ethyl ether (30.0 mL). After the organic layer was separated, it was washed with water (2*20.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The gummy residue was dried under vacuum and the solid was triturated with ether to give the title compound (0.98 g, 98%): MS (ES+) m/z 286.2 (M+1).

According to the analysis of related databases, 18711-13-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; XENON PHARMACEUTICALS INC.; US2010/173967; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, 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 4,7-Dichloroindoline-2,3-dione

4,7-Dichloro-3-hydroxy-3-(2-oxo-2-(4-(pyrrolidin-l-yl)phenyl)ethyl)indolin-2-one (EXAMPLE 10): To 4,7-dichloroindoline-2,3-dione (A) (12.5 g, 0.06 mol) in 800 mL of methanol were added l-(4-(pyrrolidin-l-yl)phenyl)ethanone (B) (45 g, 0.24 mol) and 0.5 mL of diethylamine (2). The reaction was stirred at rt for 24 hours. The solvent was removed and the residue was purified with flash chromatography (0-5% Methanol/CLLCn) to get 13.5 g of brown solid. It was purified again with flash chromatography using ethyl acetate/hexane to give 11.5 g of an off white solid. Repeating the reaction at the same scale to give another 11.5 g of product. Two batches of product were combined and recrystallized from methanol to get 20.5 g as an off white solid. 4,7-Dichloro-3-hydroxy-3-(2-oxo-2-(4-(pyrrolidin-l- yl)phenyl)ethyl)indolin-2-one (EXAMPLE 10): off-white solid; 1H NMR (DMSO-d6, 400 MHz) delta 1.96 (m, 4H), 3.30 (m, 4H), 3.65 (d, 1H, J=16 Hz), 4.29(d, 1H, J=16Hz), 6.34 (s, 1H), 6.53(d, 2H, J=8Hz), 6.88(d, 1H, J=8Hz), 7.28 (d, 1H, J=8Hz), 7.72 (d, 2H, J=8Hz), 10.97(s, 1H). Chiral separation was performed on under the following conditions. Preparatory method utilized the following:a RegisCell column L: 250 mm, IS: 50 mm, particle size: 5 mum; mobile phase: methanol/CO2, ratio: 35/65, detection wavelength: 254 nm, flow rate: 325 g/min, co-solvent flow rate 113.75 ml/min. Dissolved 19.72 g in 1000 ml of methanol, for a concentration of 0.020 g/ml. The injection volume was 25.00 ml for a total amount 0.500 g/injection. Yield was (+): 9.73 g, with optical rotation +247 at 20 C and (-): 9.26 g.

The synthetic route of 18711-13-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TOKALAS, INC.; VERNIER, Jean-michael; (82 pag.)WO2016/57698; (2016); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 18711-13-2,Some common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, molecular formula is C8H3Cl2NO2, 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 solution of 4,7-dichloroisatin (0.68 mmol, 1.0 eq) in DMF (4 mL) was added K2CO3 (0.68 mmol, 1.0 eq) at room temperature, the mixture was stirred for about 30 min, and then the propargyl bromide (0.75 mmol, 1.1 eq) was added dropwise. The mixture was stirred overnight at room temperature. Upon completion, EtOAc and H2O were added. The aqueous layer was extracted with EtOAc for several times; the combined organic layers were washed with H2O for several times to remove the DMF, and then washed with brine, dried over MgSO4 and evaporated to give the products. Compound 2, saffron solid, yield: 76%, m. p.: 151.8-153.3 C, Rf = 0.52 (petroleum ether/ethyl acetate 2/1). 1H NMR (400 MHz, CDCl3) delta 7.51 (d, J = 8.7 Hz, 1H), 7.10 (d, J = 8.7 Hz, 1H), 4.94 (d, J = 2.4 Hz, 2H), 2.34 (t, J = 2.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) delta 178.68, 157.00, 146.19, 140.48, 133.05, 126.79, 117.16, 116.11, 77.22, 73.27, 31.94.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4,7-Dichloroindoline-2,3-dione, its application will become more common.

Reference:
Article; Yu, Bin; Wang, Sai-Qi; Qi, Ping-Ping; Yang, Dong-Xiao; Tang, Kai; Liu, Hong-Min; European Journal of Medicinal Chemistry; vol. 124; (2016); p. 350 – 360;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 18711-13-2, The chemical industry reduces the impact on the environment during synthesis 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, I believe this compound will play a more active role in future production and life.

General procedure: (The reagents were purchased fromAdamas and used without further purification.) A dry 3-mL flask was chargedwith relevant isatin 5 (0.3 mmol), tert-butyl 2-aminoacetate hydrochloride 7(0.3 mmol) and benzophenone imine 8 (0.36 mmol). The reaction mixture wasstirred at room temperature for the corresponding time. After the completionof the reaction, the reaction mixture was directly purified by silica gelchromatography (ethyl acetate/petroleum ether = 1:4) to give product 6. Asolution of 6 in EA/TFA (10:1) was stirred in a 10-mL flask under roomtemperature for 3 h. The solvent was removed under vacuum. The residue wasrecrystallized in diethyl ether/petroleum ether to give product 9.

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 4,7-Dichloroindoline-2,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Huang, Huang; Xu, Yong; Mao, Fei; Zhu, Jin; Jiang, Hualiang; Li, Jian; Tetrahedron Letters; vol. 56; 4; (2015); p. 586 – 589;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, molecular formula is C8H3Cl2NO2, 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. Safety of 4,7-Dichloroindoline-2,3-dione

General procedure: A mixture of isatin derivative (1.0 mmol), trans-4-hydroxy-L-proline (0.131 g,1 mmol), and CTAB (4 mmol) in water (50mL) was stirred at 80 C for 30 min. After completion of the reaction (monitored by TLC), the contents were filtered and the residue was washed thoroughly with water until free from CTAB. Finally, the residue was crystallized from a chloroform-petroleum ether mixture to afford the desired products in excellent yields. The characterizations of the products were accomplished by spectroscopic analysis (1H, 13C NMR, FTIR, and ESI-mass) and also by comparison of the data reported in the literature.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 18711-13-2, its application will become more common.

Reference:
Article; Naskar, Subhendu; Roy, Suprakash; Sarkar, Swarbhanu; Synthetic Communications; vol. 44; 11; (2014); p. 1629 – 1634;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 18711-13-2,Some common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, molecular formula is C8H3Cl2NO2, 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.

General procedure: The NiO-SiO2 catalyst (6.5 mol%) was added to a mixture of isatin (1 mmol), malononitrile (1 mmol), and 3-methyl-1-phenyl-1H-pyrazol-5-amine (1 mmol) in EtOH, and the reaction flask was placed in an oil bath and refluxed for the appropriate time. The progress of reaction was monitored by TLC. After the completion of the reaction, the heterogeneous catalyst was recovered from the reaction mixture by filtration. The filtrate was evaporated to afford the crude solid product which was later purified by column chromatography. The solid catalyst was washed with hot EtOH and then dried in oven to reuse.

The synthetic route of 18711-13-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yagnam, Swetha; Akondi, Adinarayana Murthy; Trivedi, Rajiv; Rathod, Balaji; Prakasham, Reddy Shetty; Sridhar; Synthetic Communications; vol. 48; 3; (2018); p. 255 – 266;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 18711-13-2,Some common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, molecular formula is C8H3Cl2NO2, 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.

4,7-Dichloroisotin (4.26 g, 19.7 mmol, 1 equiv, Alfa Aesar lot 10173559) and MeOH (70 mL, 16.4 vol) were charged to a 250-mL, three-neck, round-bottom flask equipped with nitrogen line, overhead mechanical stirrer, and a temperature probe. Diethylamine (0.43 g, 0.30 equiv, Sigma- Aldrich lot SHBD5313V) was added over 1 min via syringe (the slurry becomes dark red). l-[4-(Methylamino)phenyl]ethanone 3 (11.4 g, 3.9 equiv, Sigma- Aldrich lot 01129HHV) was added in portions via a plastic funnel, over 15 min. The funnel was rinsed with MeOH (2 x 15 mL, 7.0 vol). The reaction was stirred at ambient temperature (approximately 18-20 C) and periodically sampled for in-process control (IPC) by HPLC. After 40 h of reaction, additional diethylamine was charged to the reaction via syringe (0.16 g, 0.11 equiv) and the stirring continued at ambient temperature. After 64 h, a light slurry formed. Additional diethylamine was charged to the reaction via syringe (0.13 g, 0.09 equiv) and the stirring continued at ambient temperature. After 92 h of reaction IPC by HPLC analysis showed 2.1% AUC of isatin 1 present in the reaction mixture. Additional diethylamine was charged to the reaction via syringe (0.07 g, 0.05 equiv) for a total of 0.55 equiv of base and the stirring continued at ambient temperature over the weekend. After a total of seven days, the reaction was concentrated under reduced pressure (water bath <40 C), the solid residue was dissolved in a mixture of dichloromethane (450 mL) and MeOH (50 mL) at 30 C, and adsorbed over 20 g of silica gel. Purification was carried out in a Combiflash CompanionTM XL system with a RediSep disposable flash 220 g silica gel column (catalog 69-2203-422). Elution of the residual starting material 3 was accomplished with dichloromethane (approximately 20 column vol, while the product TK- 202 was eluted with 10% methanol in dichloromethane. The product containing fractions, where product had already started to precipitate, were combined in two different lots and partially concentrated under reduced pressure. The resulting slurries were filtered and the solid cakes were washed with MeOH to afford two fractions that were dried under high vacuum at ambient temperature for 24 h, then 50 C for 24 h, to afford lot BIO-W-30-17 and lot BIO-W-30-18. The filtrate from both crystallizations were combined and subjected to a second chromatographic purification (on a 40-g RediSep Gold column, catalog 69- 2203-347) using a gradient from dichloromethane to 5% methanol in dichloromethane for elution. The product containing fractions (purity higher than 99% AUC by HPLC) were combined and the product was allowed to precipitate over 2 h. The solid was filtered off, washed with methanol, and dried under high vacuum for 24 h at 50 C to afford lot BIOW- 30-19. A second set of fractions containing product of approximately 95% AUC purity by HPLC were combined, the solid was filtered off, re-dissolved in dichloromethane, and added 20% methanol to precipitate overnight. The precipitated TK-202 was filtered and washed with methanol, then dried under high vacuum for 24 h at 50 C to afford lot BIO-W-30-16. The total combined weight of 5.99 g corresponds to 83% yield of compound. Solid is off- white (with a very pale peach to tan shade). These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4,7-Dichloroindoline-2,3-dione, its application will become more common.

Adding a certain compound to certain chemical reactions, such as: 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, belongs to indolines-derivatives compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 18711-13-2, Formula: C8H3Cl2NO2

4,7-Dichloro-3-(2-(4-cyclopropyl-3-fluorophenyl)-2-oxoethyl)-3-hydroxyindolin-2- one (EXAMPLE 17): To 4,7-dichloroindoline-2,3-dione (A) (261 mg, 1.21 mmol) in 15 mL of methanol were l-(4-cyclopropyl-3-fluorophenyl)ethanone (B) (280 mg, 1.57 mmol) and 10 drops of diethylamine (2). The reaction was stirred at 50C for 24 hours. The solvent was removed and the residue was purified with flash chromatography (0-5% Methanol/CH2C12) to get an off white solid. 4,7-Dichloro-3-(2-(4-cyclopropyl-3-fluorophenyl)-2-oxoethyl)-3- hydroxyindolin-2-one (EXAMPLE 17): off-white solid; 1H NMR (DMSO-d6, 400 MHz) delta 0.83 (m, 2H), 1.08 (m, 2H), 2.1 l(m, 1H), 3.68 (d, 1H, J=16 Hz), 4.34 (d, 1H, J=16Hz), 6.43(s, 1H), 6.90(d, 1H, J=8Hz), 7.11 (m, 1H), 7.30 (d, 1H, J=8Hz), 7.60(d, 1H, J=8Hz),7.68 (d, 1H, J=8Hz), 10.96 (s, 1H). Chiral separation was performed by a method substantially similar to the method described above. LC screening was performed with: column: AD-H, 250 mm x 4.6 mm, 5 mum, hexane/ethanol (65/35), 1.5 ml/min, injection volume: 10.0 mu, pressure: 102.9 bar. Peak 1 : retention time: 5.40 min, width: 0.171 min, area: 4502.21, area %: 50.08. Peak 2: retention time: 7.23 min, width: 0.239 min, area: 4488.43, area %: 49.92.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4,7-Dichloroindoline-2,3-dione, and friends who are interested can also refer to it.

Electric Literature of 18711-13-2, These common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, 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.

4,7-Dichloro-3-(2-(4-cyclopropylphenyl)-2-oxoethyl)-3-hydroxyindolin-2-one EXAMPLE 7): To 4,7-dichloroindoline-2,3-dione (A) (300 mg, 1.39 mmol) in 15 niL of methanol were added l-(4-cyclopropylphenyl)ethanone (B) (0.9 g, 5.5 mmol) and 10 drops of diethylamine (2). The reaction was stirred at 50C for 24 hours. The solvent was removed and the residue was purified with flash chromatography (0-5% Methanol/CH2C12) to get an off white solid. 4,7-Dichloro-3-(2-(4-cyclopropylphenyl)-2-oxoethyl)-3-hydroxyindolin-2- one (EXAMPLE 7): off-white solid; 1H NMR (DMSO-d6, 400 MHz) delta 0.76 (m, 2H), 1.06 (m, 2H), 2.0(m, 1H), 3.65 (d, 1H, J=16 Hz), 4.35 (d, 1H, J=16Hz), 6.43(s, 1H), 6.89(d, 1H, J=8Hz), 7.19 (d, 2H, J=8Hz), 7.30 (d, 1H, J=8Hz), 7.79 (d, 2H, J=8Hz), 10.97 (s, 1H).

Statistics shows that 4,7-Dichloroindoline-2,3-dione is playing an increasingly important role. we look forward to future research findings about 18711-13-2.

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 18711-13-2 as follows. category: indolines-derivatives

General procedure: Sulfonated-beta-cyclodextrin (beta-CD-SO3H) (76 mg, 0.06 mmol) was dissolved in water (5 mL) at RT by stirring to get the clear solution in 50 mL round bottom ask. Further, isatin 2 (0.31 mmol) and tryptamine 1a/isotryptamine 1b (0.31 mmol) were added to the solution under constant stirring and mixture was heated at 80 C for 8-12 h. The progress of the reaction was monitored by TLC. After completion of reaction, it was cooled to room temperature, water was added to it. The aqueous phase was extracted with ethylacetate. The organic extracts were combined, washed with brine and dried over sodium sulfate. The solvent was evaporated in vacuo and the crude product obtained was puried by column chromatography using chloroform/methanol (99:1) as an eluent furnishing the product. The spectral and analytical data of all the reported products is consistent with the previous (6c,d,f) reports.

According to the analysis of related databases, 18711-13-2, the application of this compound in the production field has become more and more popular.