Category: indolines-derivatives

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. 61-70-1, name is 1-Methylindolin-2-one, A new synthetic method of this compound is introduced below., HPLC of Formula: C9H9NO

General procedure: Isatin (0.1 mol, 14.7 g) was dissolved in DMF (60 mL) and finely ground anhydrous K2CO3 (0.15 mol,20.7 g) was added under stirring. RX (0.15 mol) was added dropwise and mixture was heated at 60-70C for 3 h (as alkylation reagent RX were used Me2SO4, EtI, n-PrBr, AmBr, BnCl, PMBCl,respectively). After cooling to room temperature mixture was poured into ice water (200 mL).Precipitated orange solid was filtereted, washed with water and recrystallized from ethanol (95%) togive N-alkylated isatins as red crystalls in 37-92% yield. The purity of obtained compounds weredetermined by melting points, which corresponded to those published in the literature (ref. 2-4).N-Substituted isatin (10 mmol) was mixed with 16 M N2H4¡¤H2O (15 mL). The suspension was heatedat reflux 3 h (caution: rapid gas evolution), then it was cooled to room temperature, diluted with waterS4(40 mL) and extracted with EtOAc (3 x 25 mL). Organic phase was washed with water (25 mL), brine (25 mL), then it was dried over Na2SO4 and evaporated under reduced pressure to give the desired product. The latter was recrystallized from hexane and small amount of EtOAc to give N-substituted indolin-2-one as yellow solid in 47-96% yield. The purity of obtained compounds were determined by melting points and 1H NMR spectra data, which corresponded to those published in the literature (ref. 5,6).N-Substituted indolin-2-one (2 mmol) were dissolved in dry DMF (5 mL) and NaH (60% dispersion in mineral oil, 6 mmol, 240 mg) was portionwise added carefully at a temperature of -15 C. When the rapid evolution of H2 stops, the mixture allowed to stir for 10 min. Then solution of 1,2-dibromoethane (508 mg, 2.7 mmol) in dry DMF (3 mL) was added to the mixture. The latter was warmed to room temperature and stirred overnight. Then it was cooled with ice, diluted with water (20 mL) and extracted with PhMe (2 x 15 mL). Organic phase was washed with water (2 x 15 mL), brine (15 mL) and then it was dried over Na2SO4. Evaporation under reduced pressure gave the desired product. The latter was washed with hexane to remove mineral oil or purified by flash column chromatography (eluent: hexane/CH2Cl2). The spiro[cyclopropane-1,3′-indolin]-2′-ones 1 are yellow solids, except N-amyl substituted spiro[cyclopropane-1,3′-indolin]-2′-one, which is brown liquid. The purity of obtained compounds were determined by 1H NMR spectra data. Corresponding cyclopropanes were previously known in the literature (ref. 7-11).

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:
Article; Buev, Evgeny M.; Moshkin, Vladimir S.; Sosnovskikh, Vyacheslav Y.; Tetrahedron Letters; vol. 59; 37; (2018); p. 3409 – 3412;,
Indoline – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 2058-72-2, name is 5-Bromo-1-methylindoline-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 2058-72-2, Product Details of 2058-72-2

General procedure: To a stirring mixture of catalyst 1a (0.005 mmol) and cyclohexanone/acetone (5 mmol) in water (500 muL), additive DNP (0.920 mg, 0.005 mmol) was added at 25 C and the mixture was allowed to stir for 5 min followed by addition of isatin derivative (0.5 mmol). The mixture was stirred for 20-96 h and the progress of the reaction was monitored at regular intervals by TLC. On the completion of reaction, saturated solution of NH4Cl (5 mL) was added to it and resulting mixture was extracted with ethyl acetate (3¡Á15 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain crude aldol product. The column chromatography on silica gel (60-120 mesh) using hexane/ethyl acetate as an eluent gave the corresponding aldol adducts as a syn/anti mixture. The enantiomeric excess of aldol addition products was determined by chiral HPLC. The diastereoselectivity of product was determined by HPLC of crude reaction mixture. Racemic standards were prepared using (¡À) 3-methyl-1-morpholinobutan-2-amine catalyst synthesized form (¡À) valine.

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:
Article; Kumar, Akshay; Chimni, Swapandeep Singh; Tetrahedron; vol. 69; 25; (2013); p. 5197 – 5204;,
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Synthetic Route of 334952-09-9, 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. 334952-09-9, name is 2-Oxoindoline-6-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

Intermediate 2a (2Og) is dissolved in DMF (15OmL) and carbonyldiimidazole (19g) is added. The reaction is then heated to 70C for 1 hour after which the reaction is cooled to room temperature. Aminoacetaldehyde diethylacetal (16.5mL) is added and allowed to react at room temperature overnight. The solvent is then removed under reduced pressure and the residue is purified by LC (SiO2, DCM:MeOH 90: 10) to yield the desired compound 1 (1 Og).

The chemical industry reduces the impact on the environment during synthesis 2-Oxoindoline-6-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG; WO2006/64044; (2006); A1;,
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Related Products of 603-62-3, 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. 603-62-3, name is 3-Nitrophthalimide belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Intermediate 1; Preparation of (2-methyl-l,3-dioxo-2,3-dihydro-lH-isoindol-4-yl)acetic acid; Step 1 : 4-Amino-l,3-isoindolinedione; A solution of 3-nitrophthalimide in ethylacetate was treated with 10% palladium on charcoal (10 wt. %) and hydrogenated at 20 psi for 2h. The catalyst was filtered through celite and the filterate was evaporated to give the crude product (97%) which was used without purification in the next step. 1H-NMR (delta ppm, DMSO-J6, 300 MHz): 10.85 (br. s, IH); 7.39 (t, J = 7.8, IH); 6.93 (d, J = 8.4, IH); 6.88 (d, J = 6.9); 6.38 (br. s, 2H).

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, 3-Nitrophthalimide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLENMARK PHARMACEUTICALS, S. A.; WO2009/118596; (2009); A2;,
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Related Products of 19155-24-9, 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 19155-24-9 as follows.

Preparation of l-(3-chloropropyl)-3,3-dimethylindolin-2-one; [0231] A solution of 3,3-dimethylindolin-2-one (1.843 g, 11.43 mmol, 1 equiv) in N,N- dimethylformamide was cooled to 0¡ãC. Sodium hydride (60percent dispersion) (503 mg, 12.58 mmol, 1.1 equiv) was slowly added and the reaction was stirred as such until all bubbling had stopped. 1 – bromo-3-chloropropane (3.37 ml, 34.3 mmol, 3 equiv) was added to the reaction mixture in one portion. The reaction was allowed to warm to ambient temperature and stirred as such for 16 h. The crude mixture was partitioned between ethyl acetate and water. The organic layer was dried over MgSO i, filtered, concentrated, and the residue was purified using the Biotage flash chromatography system (SNAP 50 g cartridge, R/= 0.5, gradient – 5percent>-30percent> ethyl acetate in hexanes) to afford the title compound as a light orange oil (2.38 g, 87percent); ‘i/NMR (400 MHz, DMSO-i/6): delta 1.26 (s, 6H); 1.98-2.14 (m, 2H); 3.65 (t, 2H, J= 6 and 6.8 Hz); 3.77-3.81 (m, 2H); 7.02-7.07 (m, 2H); 7.24-7.28 (m, 1H); 7.33-7.35 (m, 1H); MS for C13H16C1N0 m/z 237.99 (M+H)+.

According to the analysis of related databases, 19155-24-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ALTOS THERAPEUTICS, LLC; LUEHR, Gary, W.; SUNDARAM, Arathi; JAISHANKAR, Priyadarshini; PAYNE, Philip, W.; DRUZGALA, Pascal; WO2011/160084; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-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. Application In Synthesis of 2-(Chloromethyl)isoindoline-1,3-dione

General procedure: The initial carbonyl compound (50 mmol) was dissolved/suspended in ethanol (50 mL) and magnetically stirred with thiosemicarbazide (50 mmol) and catalytic amounts of acetic acid for 8-24 h at room temperature. The obtained thiosemicarbazone was filtered, washed with appropriate solvent (n-hexane, petroleumether or diethyl ether) and dried under vacuum. The intermediate thiosemicarbazone (50 mmol) reacted with ethyl bromoacetate (50 mmol), in methanol (50 mL) and sodium acetate (50 mmol) at room temperature under magnetic stirring for 24 h. The resulting 4-thiazolidinone was poured on ice, filtered or extracted with chloroform (3 x 100 mL) and purified by column chromatography (SiO2, ethyl acetate/n-hexane). Then, the obtained thiazolidinone (50 mmol) was dissolved/suspended in 50 mL of anhydrous acetone in the presence of anhydrous potassium carbonate (50 mmol), and reacted with equimolar amounts of 4-nitrobenzyl bromide, 1-(chloromethyl)naphthalene and N-(chloromethyl)phthalimide for 24-48 h. The product was poured on ice, filtered or extracted with chloroform (3 x 50 mL) and purified by column chromatography (SiO2, ethyl acetate/n-hexane) in order to obtain the title compoundsin high yields. 7.1.60 2-((2-(2-(Heptan-3-ylidene)hydrazono)-4-oxothiazolidin-3-yl)methyl)isoindoline-1,3-dione (8C) White powder, mp 70-74 C, 86% yield; 1H NMR (400 MHz, CDCl3): delta 0.82-0.93 (m, 2H, CH2, 3H, CH3), 1.08-1.12 (m, 1H, CH2), 1.30-1.37 (m, 3H, CH3), 1.51-1.55 (m, 1H, CH2), 2.24-2.32 (m, 2H, CH2), 2.36-2.44 (m, 2H, CH2), 3.82 (s, 2H, CH2, thiazolidinone), 5.71 (s, 2H, ArCH2), 7.73-75 (m, 2H, Ar), 7.85-7.86 (m, 2H, Ar).

The synthetic route of 17564-64-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; De Monte, Celeste; Carradori, Simone; Bizzarri, Bruna; Bolasco, Adriana; Caprara, Federica; Mollica, Adriano; Rivanera, Daniela; Mari, Emanuela; Zicari, Alessandra; Akdemir, Atilla; Secci, Daniela; European Journal of Medicinal Chemistry; vol. 107; (2016); p. 82 – 96;,
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Related Products of 239463-85-5,Some common heterocyclic compound, 239463-85-5, name is (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, molecular formula is C26H31N3O8, 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 slurry of SI-I (769 g, 1.50 mol) as the tartrate salt (e.e. 98.3%) in dichloromethane (2 L) was added dropwise an aqueous solution of sodium hydroxide (5 N, 126 g, 3.15 mol) at 10 C, all in a round bottom flask (5 L). The reaction mixture was stirred until the pH was 11. The organic layer was separated and the aqueous layer was extracted with dichloromethane twice (500 ml 2). The combined organic layer was washed with water to neutrality, dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give the SI-II (531 g, 97.5%, HPLC 98.2%) as a light yellow oil.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, its application will become more common.

Reference:
Article; Liu, Hui; Lv, Fei; Liu, Yuan; Organic Preparations and Procedures International; vol. 51; 3; (2019); p. 287 – 293;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 21544-81-0,Some common heterocyclic compound, 21544-81-0, name is 4,6-Dimethoxyindoline-2,3-dione, molecular formula is C10H9NO4, 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.

Hydrogen peroxide (30 % solution in water, 30 ml) was added dropwise to a stirred solution of 4,6-dimethoxy-2,3-dioxoindoline (27 g) in a concentrated aqueous sodium hydroxide solution (33 %, 220 ml). The resultant mixture was stirred at ambient temperature for 10 minutes. Ice was added and the basicity of the mixture was reduced to pH9 by the addition of concentrated aqueous hydrochloric acid and the mixture was then acidified to pH3.5 by the addition of glacial acetic acid. The resultant precipitate was isolated, washed with water and dried overnight under vacuum to give 2-amino-4,6-dimethoxybenzoic acid (15.9 g); NMR Spectrum : (DMSOd6) 3.7 (s, 3H), 3.78 (s, 3H), 5.79 (s, 1H), 5.92 (s, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4,6-Dimethoxyindoline-2,3-dione, its application will become more common.

Reference:
Patent; AstraZeneca AB; EP1292594; (2004); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 110568-64-4, The chemical industry reduces the impact on the environment during synthesis 110568-64-4, name is 6-Nitroisoindolin-1-one, I believe this compound will play a more active role in future production and life.

Step d:[00296] A mixture of 5-nitro-2,3-dihydro-isoindol-l-one derivative (l eq), 10% Pd-C (0.05 eq) and 10 mL AcOEt is hydrogenated at room temperature for 6hrs. The catalyst is removed by filtration through Celite and the filtrate is evaporated to afford the title compound.

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, 6-Nitroisoindolin-1-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GALAPAGOS NV; MENET, Christel, Jeanne, Marie; BLANC, Javier; HODGES, Alastair, James; BURLI, Roland, Werner; BRECCIA, Perla; BLACKABY, Wesley, Peter; VAN ROMPAEY, Luc, Juliaan, Corina; FLETCHER, Stephen, Robert; WO2010/10184; (2010); A1;,
Indoline – Wikipedia,
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Application of 317-20-4, 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. 317-20-4 name is 7-Fluoroisatin, 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.

General procedure: In a 15 mL quartz tube equipped with a magnetic stirrer bar, isatin (1 mmol), 1,3-dicarbonyl compound (1 mmol), malononitrile (1 mmol), and Na2 eosin Y (0.02 mmol) were added successively in ethyl lactate/water (3:1, 2 mL). The reaction tube was exposed to green LED (520e525 nm, 10 W) irradiation at a distance of approximately 3 mm from bottom of the tube (SI, Fig. S1) at room temperature in air with stirring for an appropriate time. The reaction progress was monitored by TLC. Upon completion, water was added to the mixture and the solid precipitate was filtered and washed with ethanol to obtain the desired pure product.

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

Reference:
Article; Chen, Meng-Nan; Di, Jia-Qi; Li, Jiao-Mian; Mo, Li-Ping; Zhang, Zhan-Hui; Tetrahedron; (2020);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem