Tag: M.W=200-300

99365-40-9, name is 6-Bromoindolin-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. Safety of 6-Bromoindolin-2-one

NaHC03 (23 g, 283 mmol, 2.0 eq) and di-tert-butyl dicarbonate (46 mL, 212 mmol, 1.5 eq) were added to a stirred solution of 6-bromoindolin-2-one (30 g, 141.5 mmol, 1.0 eq) in THF (300 mL) at rt. The mixture was refluxed for 3 h, then cooled to rt, diluted with water (100 mL) and extracted with EtOAc (2x 100 mL). The combined organic layers were washed with brine (50 mL), dried and evaporated under reduced pressure. The raw product was purified by column chromatography [silica gel 100-200 mesh, PE/EtOAc = 9:1]. White solid. Yield: 35 g, (79%). 1H NMR (400 MHz, CDCI3, delta ppm): 8.03 (d, J = 1.2 Hz, 1H), 7.27 (dd, J = 8.0, 1.6 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 3.58 (s, 2H), 1.64 (s, 9H).

The synthetic route of 99365-40-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GRUeNENTHAL GMBH; KONETZKI, Ingo; JAKOB, Florian; WAGENER, Markus; WELBERS, Andre; HESSLINGER, Christian; (168 pag.)WO2017/108204; (2017); 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 675109-26-9 as follows. SDS of cas: 675109-26-9

6-Bromoisoindolin-l-one (4 g, 18.9 mmol) was suspended in 70 ml of THF and cooled to 0-5C. Sodium hydride (60% in mineral oil) (1.5 g, 37.7 mmol, 2 equiv.) was added in portions at 0-5C and after 5 minutes (2RS)-2-bromo-2-phenyl-acetic acid (4.34 g, 20.2 mmol, 1.07 equiv.) were added and the mixture was stirred at 0-5 C for 2 hours. The reaction mixture was extracted with 1M HC1 solution and twice with ethyl acetate. The organic layers were dried over sodium sulfate and evaporated to dryness to obtain the desired (2RS)-2-(6-bromo-l-oxo-isoindolin-2-yl)-2- phenyl-acetic acid (5.78 g, 89 % yield) as a white solid, MS: m/e = 345.9/347.9 (M+H+).

According to the analysis of related databases, 675109-26-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; C4 THERAPEUTICS, INC.; DUPLESSIS, Martin; JAESCHKE, Georg; KUHN, Bernd; LAZARSKI, Kiel; LIANG, Yanke; NAGEL, Yvonne Alice; RICCI, Antonio; RUEHER, Daniel; STEINER, Sandra; (46 pag.)WO2019/149922; (2019); A1;,
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

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. 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 201940-08-1

Tris(dibenzylideneacetone)dipalladium(0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added into a solution of 5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) in toluene (15 mL). The reaction mixture was purged with argon for 5 minutes and then N-methylpiperazine (1.33 mL, 12 mmol) was added and the mixture and stirred at 80 C. for 4 hours. After the completion of the reaction (monitored by TLC) the solvent was removed under vacuum, water (3 mL) was added, and the reaction mixture was extracted with dichloromethane (3*30 mL). The combined organic extracts were dried over Na2SO4. The solvents were removed under vacuum and the residue was purified on silica gel (Biotage; eluting solvents 5% MeOH in dichloromethane) to afford tert-butyl 5-(4-methylpiperazin-1-yl)isoindoline-2-carboxylate as brown solid (1.75 g, 55% yield); 1H NMR (400 MHz, MeOH-d4) delta ppm 7.16-7.12 (m, 1H), 6.92-6.88 (m, 2H), 4.59-4.53 (m, 4H), 3.19-3.17 (m, 4H), 2.63-2.60 (m, 4H), 2.34 (s, 3H), 1.51 (9H, s).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 201940-08-1.

Reference:
Patent; Malamas, Michael; Makriyannis, Alexandros; Lamani, Manjunath; Farah, Shrouq I.; US2019/152917; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 6941-75-9, name is 5-Bromoisoindoline-1,3-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 6941-75-9, Computed Properties of C8H4BrNO2

EXAMPLE 5; Step 5A: Bromophthalimide 5a (13.0 g, 57.8 mmol) was added in six portions over 30 minutes to a stirred suspension of zinc powder (4.50 g, 69.2 mmol) and copper (II) sulfate pentahydrate (0.060 g, 0.25 mmol) in aqueous sodium hydroxide (2 M, 71 mL) at 0 C (ice-bath. ) The mixture was stirred at 0 C for an additional 30 minutes, and at room temperature for 2.5 h to complete the reaction. After filtering, the reaction solution was neutralized to pH 7 with 20% hydrochloric acid, diluted with 100 mL of ethanol, and then extracted with ethyl acetate. The extract was washed with brine, dried with MgS04 and concentrated in vacuo to afford 12.5 g (95%) of 5b as a yellow solid, LC-MS 210 (MH+-H20.)

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; NEUROCRINE BIOSCIENCES, INC.; WO2005/103039; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

20780-72-7, name is 4-Bromoisatin, 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. name: 4-Bromoisatin

To 4-bromoindoline-2,3-dione (200 mg, 0.89 mmol) in 5 ml DMF was added 4- Fluorobenzylbromide (0.120 ml, 0.98 mmol) then add NaH (35 mg, 0.89 mmol) and stir at room temperature overnight. Work up by adding water and EtOAc and extract three times with EtOAc. Pool all organics and wash one time with brine then dry over sodium sulfate, filter and concentrate to dryness. The residue was purified by chromatography over silica gel (eluted with Hexanes/EtOAc 99:1 to 50:50) to provide 270 mg (90percent) of product.

The synthetic route of 20780-72-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SCHERING CORPORATION; WO2009/73777; (2009); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 5394-18-3, name is 2-(4-Bromobutyl)isoindoline-1,3-dione, A new synthetic method of this compound is introduced below., Product Details of 5394-18-3

To a cooled solution of 1 /-/-imidazole (200 mg, 3.085 mmol, 1.05 eq) in DMF (7 ml_), NaH 60% in mineral oil (136 mg, 3.393 mmol, 1.1 eq.) was added portionwise and the mixture was stirred for 10 min. Afterwards, a solution of 2-(4-bromobutyl)-2,3-dihydro-1 7Aisoindole-1,3-dione (870 mg, 3.085 mmol, 1 eq.) in DMF (3 ml.) was added dropwise. The reaction was continued at 60C for further 16 h. The reaction was quenched with water and diluted in AcOEt. The layers were separated. Organic layer was dried, filtered off and concentrated in vacuo. The residue was purified by FCC (SiHP, DCM: MeOH 95:5) to afford the title compound (323 mg, 1.2 mmol, yield 40%) as a white solid. ESI-MS: 270 [M+H]+ 1H NMR (300 MHz, Chloroform-o) d 7.89 – 7.85 (m, 2H), 7.77 – 7.73 (m, 2H), 7.50 (t, J= 1.1Hz, 1H), 7.07 (t, J= 1.1Hz, 1H), 6.93 (t, J= 1.3 Hz, 1H), 4.02 (t, J= 7.0 Hz, 2H), 3.74 (t, J= 6.8 Hz, 2H), 1.91 – 1.79 (m, 2H), 1.78 – 1.64 (m, 2H).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; RYVU THERAPEUTICS S.A.; DOBRZANSKA, Monika Patrycja; ZAWADZKA, Magdalena Izabela; RADZIMIERSKI, Adam; TOPOLNICKI, Grzegorz Witold; CWIERTNIA, Grzegorz Wojciech; MAHAJAN, Tushar Ravindra; FABRITIUS, Charles-Henry; CHMIELEWSKI, Stefan; GLUZA, Karolina Maria; ALVAREZ, Jose; ROGACKI, Maciej Krzysztof; MROCZKOWSKA, Magdalena; (215 pag.)WO2019/238786; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 5181-35-1, 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 5181-35-1 as follows.

To a solution of 2-(2- bromoethoxy)isoindoline-l,3-dione (20 g, 74 mmol) in dimethylformamide (100 ml) added 5-(2- tertiary-butyl-dimethyl-silanyloxy ethyl)- lH-tetrazole (14.81 g, 74 mmol) at 25-30 C under stirring followed by cesium carbonate ((29 g, 88 mmol) in portion wise under stirring. The reaction was continued further at same temperature for 16 hrs and filtered. The filtrate was slowly poured onto chilled water (700 ml) under stirring and continued stirring for 30 minutes. The formed precipitates were filtered and washed with water (70 ml). The solid compound was dried at 40 C for 2 hour under high vacuum to yield crude compound 17.2 g. The crude compound was column purified (silica gel 60-120 mesh size) using hexane and acetone as an eluent. The non-polar spot isolated at 8-12% concentration of acetone in hexane, yielded 8 g of 2-{2-[5-(2-tertiary-butyl- dimethyl-silanyloxy ethyl)-2H-tetrazol-2-yl]ethoxy}-lH-isoindole-l,3(2H)-dione. The polar spot was isolated at 16-20% concentration of acetone in hexane and yielded 4.2 g of 2-{2-[5-(2-tertiary- butyl-dimethyl-silanyloxy ethyl)-lH-tetrazol-l-yl]ethoxy}-lH-isoindole-l,3(2H)-dione as white solid. Analysis: Mass: 418.3 (M+H); for Molecular weight: 417 and Molecular formula: Ci9H27N504Si. 1HNMR (CDCI3): delta.83-7.74 (m, 4H), 5.00 (t, 2H, J=6 Hz), 4.73 (t, 2H, J=6 Hz), 3.98 (t, 2H, J=6.8 Hz), 3.08 (t, 2H, J=7.2 Hz), 0.837 (s, 9H), 0.002 (s, 6H).

According to the analysis of related databases, 5181-35-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; WOCKHARDT LIMITED; TADIPARTHI, Ravikumar; PATIL, Vijaykumar Jagdishwar; DEKHANE, Deepak; SHAIKH, Mohammad Usman; BIRAJDAR, Satish; DOND, Bharat; PATEL, Mahesh Vithalbhai; (100 pag.)WO2017/81615; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 675109-26-9, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 675109-26-9 name is 6-Bromoisoindolin-1-one, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Example 265: (S)-3-Oxo-N-((4-(trifluoromethyl)phenyl)(3-(trifluoromethyl)- pyridin-2-yl)methyl)isoindoline-5-carboxamide To a 25 mL round bottom flask containing (S)-(4-(trifluoromethyl)- phenyl)(3 -(trifiuoromethyl)pyridin-2-yl)methanamine hydrochloride (Intermediate 1) (120 mg, 0.336 mmol) was added toluene (3 mL). The resulting mixture was stirred at rt for 2 min. At this time,sodium carbonate (143 mg, 1.346 mmol), 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (3.89 mg, 6.73 muiotaetaomicron), palladium (II) acetate (1.5 mg, 6.7 muiotaetaomicron) and 6-bromo-2,3-dihydro-isoindol-l-one (71.3 mg, 0.336 mmol) were added to the flask. The reaction vessel was flushed with argon and then left under 1.0 atm of carbon monoxide gas (from a lecture bottle, in hood). The flask was heated to 85 C overnight, filtered though Celite brnad filter agent, and eluted with EtOAc. Purification by reverse phase HPLC, and concentration of the containing fractions gave (S)-3-oxo-N-((4-(trifiuoromethyl)- phenyl)(3-(trifiuoromethyl)pyridin-2-yl)methyl)isoindoline-5-carboxamide as a yellow foamy solid. 1H NMR (300MHz , CDC13): delta ppm 8.92 (d, J = 4.5 Hz, 1H), 8.40 (d, J = 7.7 Hz, 1 H), 7.60 – 7.56 (m, 5 H), 7.46 – 7.48 (m, 2 H), 6.90 (d, J = 7.6 Hz, 1 H), 4.54 (s, 2 H). MS 480.1 (M+H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromoisoindolin-1-one, and friends who are interested can also refer to it.

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. Formula: C10H9Cl2NO

Preparation of 5-(2-(4-(l ,2-benzisothiazol-3-yl)-1 -piperazinyl)ethvD-6-chloro-l ,3-dihydro-2H-indol-2-one(Ziprasidone)In a 50 ml 3 necked round bottom flask there were placed 1 gram (4.56 mmol) of 3-piperazinylbenzo[d]isothiazole; 1.25 grams (5.43 mmol) of 6-chloro-5-(2-chloroethyl)indolin-2-one; 50 mg of potassium iodide; 0.82 gram (5.94 mmol) ofpotassium carbonate and 3 ml of sulfolane. The contents of the flask were heated to 95C to 100 C. The reaction was monitored by HPLC. After completion of the reaction, 50ml of DM water was added to the reaction mixture and stirred. The product was filtered off and washed with water and dried to obtain 1.41 grams (75%) of 5-(2-(4-(l,2-benzisothiazol-3-yl)-l-piperazinyl)ethyl)-6-chloro-l,3-dihydro-2H-indol-2-one. The crude product was purified by IPA and/ or THF. The product matched the spectra of a standard NMR and showed the correct retention time by HPLC with 98.0% assay. The melting point of the compound was found to be 218C -220 C, and was found to conform with the melting point of 218 -220 C as disclosed in US. 5,206,366. Example 3Preparation of 5-(2-(4-(‘l,2-benzisothiazol-3-vD-l-piperazinvDethvl)-6-chloro-l,3-dihydro-2H-indol-2-one(Ziprasidone)In glass-lined reactor placed 21.1 Kg (96.34 mole) of 3-piperazinylbenzo [d]isothiazole; 31 kg (134.7 moles) of 6-chloro-5-(2-chloroethyl)indolin-2-one; 1.1 kg ofpotassium iodide; 20.0 kg (111.92 mole) of potassium carbonate and 63.2 lit ofsulfolane. The contents of the flask were initially heated to 75C to 80 C for 2 hrs.Then temperature was raised to 95C to 100 C and stirred till completion of thereaction. After completion of the reaction 210 lit of DM water was added to the reaction mixture and stirred. The product was filtered off and washed with water and dried to obtain 29.75 kg of 5-(2-(4-(l,2-benzisothiazol-3-yl)-l-piperazinyl)ethyl)-6-chloro-l,3-dihydro-2H-indol-2-one (Ziprasidone).

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