Category: indolines-derivatives

Electric Literature of 2058-72-2, 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. 2058-72-2 name is 5-Bromo-1-methylindoline-2,3-dione, 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: The mixture of corresponding 2-amino-4-arylimidazoles 1 (1.0 mmol), isatin 18 (1.0 mmol) and ethyl 2-cyanoacetate 15 (1.0 mmol) in 2 mL of 2-propanol was refluxedduring 50-60 min. After cooling, the solid products 20were filtered off and crystallized from iPrOH.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromo-1-methylindoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Article; Lipson, Victoria V.; Pavlovska, Tetiana L.; Svetlichnaya, Nataliya V.; Poryvai, Anna A.; Gorobets, Nikolay Yu.; Van Der Eycken, Erik V.; Konovalova, Irina S.; Shiskina, Svetlana V.; Borisov, Alexander V.; Musatov, Vladimir I.; Mazepa, Alexander V.; Beilstein Journal of Organic Chemistry; vol. 15; (2019); p. 1032 – 1045;,
Indoline – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-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 446292-08-6, HPLC of Formula: C22H19N3O6

2-({(5S) -2-oxo-3-[4- (3-oxo-4-morpholinyl) phenyl] -1,3-oxazolidin-5- yl} methyl)-1,3(2H) -dione (Formula 5) were added 75 ml of ethanol and 8.1 ml of a methylamine solution (concentration in water 40%) was added.The reaction mixture was then diluted with 60In Heating, Stir at this temperature for 2 hours.Confirm that the reaction is completed, and while maintaining the temperature, dilute the solution with 50 ml of ethanol and 3.04 ml of phosphoric acid, and slowly add the solution to the reaction solution. After confirming that the crystallization of the product was initiated and cooling to 20 C, the precipitated reaction product was filtered under suction. The resulting solid was dispersed in 110 ml of methanol, refluxed for 30 minutes and stirred, and then cooled to room temperature. The resulting crystals were filtered,And dried at 50 DEG C for 4 hours to obtain 11.1 g of morpholine diphosphate (Formula 2). (Yield: 96.0%)

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, (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; IL DONG PHARMACEUTICAL CO., LTD.; LEE, Ki Yong; KWON, Jae Wook; SEO, Myeong Won; KANG, Jae Hoon; (15 pag.)KR2017/98031; (2017); A;,
Indoline – Wikipedia,
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Electric Literature of 446292-08-6,Some common heterocyclic compound, 446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, molecular formula is C22H19N3O6, 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.

100 g (S)-2-((2-oxo-3-(4-(3-o o-mo holino)phenyl)oxazol^din-5- yl)methyl)isoindoline-l,3-dione of Formula (I), 1000 ml Methanol and 119 g methyl amine were added to RBF at 25C to 35C. The reaction was heated to 60C to 65C for 1-2 hours. To the reaction mass formic acid (15g) was added till to pH 5.5 to 6.0 and maintained for 30 minutes. The reaction mass was cooled to 45 to 50C and maintained for 30 minutes. The reaction mass was cooled to 25 to 35C andmaintained for 30 minutes. The product was filtered and washed with methanol (50 ml x 2) afforded the formate salt of (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3- yl)phenyl)morpholin-3 -one of Formula (JF).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, its application will become more common.

Reference:
Patent; CADILA HEALTHCARE LIMITED; DWIVEDI, Shriprakash, Dhar; PRASAD, Ashok; PAL, Daya, Ram; SHARMA, Mukul, Hari, Prasad; JAIN, Kuldeep, Natwarlal; PATEL, Naitik, Bharatbhai; WO2013/98833; (2013); A2;,
Indoline – Wikipedia,
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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. 5332-26-3, name is 2-(Bromomethyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Formula: C9H6BrNO2

General procedure: The benzofused N-heteroaromatic alkynes 2, 5, and 8 weresynthesized by reacting benzimidazole (1.0 mmol),benzotriazole (1.0 mmol), or carbazole (1.0 mmol) withpropargyl bromide (1.2 mmol) in the presence of potassiumcarbonate (2.0 mmol) using dimethylformamide bycontinuous stirring at 10-25 C up to 8-10 h [32]. For thesynthesis of target compounds, solution of aromatic bromides(1.0 mmol) in dimethylformamide was taken in around-bottomed flask and aqueous solution of sodium azide(3.0 mmol) was added, thereafter, stirred the reactionmixture for 1 h at 25-40 C. To the above reaction mixture,benzofused N-heteroaromatic alkyne 2 (1.0 mmol), 5(1.0 mmol), or 8 (1.0 mmol) was added followed by coppersulfate pentahydrate (5 mol %) and sodium ascorbate(10 mol %) [33], then, stirred the reaction contents overnight.The progress of reaction was monitored by thin layerchromatography. After the completion of reaction, ice-colddistilled water was added to the reaction mixture andproduct was extracted with ethyl acetate (50 cm3 9 3).The organic layer was washed with aqueous ammoniasolution followed by brine solution and dried using anhydroussodium sulfate. Filtered and evaporated the solventunder vacuum to get crude product which was furtherpurified by column chromatography using hexane:ethylacetate (7:3) as eluent.

According to the analysis of related databases, 5332-26-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kaushik; Kumar, Krishan; Lal, Kashmiri; Narasimhan, Balasubramanian; Kumar, Ashwani; Monatshefte fur Chemie; vol. 147; 4; (2016); p. 817 – 828;,
Indoline – Wikipedia,
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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. 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, A new synthetic method of this compound is introduced below., COA of Formula: C9H7NO3

2-Oxo-3-(4-oxo-2,4,6,7-tetrahydro-pyrano[3,4-c]pyrrol-1-ylmethylene)-2,3-dihydro-1H-indole-5-carboxylic acid 2-Oxo-2,3-dihydro-1H-indole-5-carboxylic acid was condensed with 4-oxo-2,4,6,7-tetrahydro-pyrano[3,4-c]pyrrole-1-carbaldehyde to give the title compound. MS m/z 325.2 [M++1].

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; Tang, Peng Cho; Miller, Todd A.; Li, Xiaoyuan; Zhang, Ruofei; Cui, Jinrong; Huang, Ping; Wei, Chung Chun; US2002/42427; (2002); A1;,
Indoline – Wikipedia,
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Reference of 32692-19-6, 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 32692-19-6 as follows.

To a solution of 5-nitroindoline (5.718 g) in DMF (60 mL) at 0C was sequentially added Nai l (1.348 g, 60% dispersion in mineral oil) and l-bromo-2-methoxyethane (5.368 g). The mixture was stirred at 0C for 2 h, and then was allowed to warm up to room temperature and stirred for another 3 h. At this point, TLC indicated the reaction to be complete. The reaction mixture was poured onto ice-water. The precipitate was collected, and re-dissolved in ethyl acetate. The organic layer was washed with water, brine and concentrated under reduced pressure to afford the desired product 1 (7.292 g, 94%, M+H+= 223.3) as a yellow solid.

According to the analysis of related databases, 32692-19-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ACEA BIOSCIENCES INC.; XU, Xiao; WANG, Xiaobo; MAO, Long; ZHAO, Li; XI, Biao; WO2015/6754; (2015); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 90725-50-1, 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. 90725-50-1, name is 6-Bromo-3-methylindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

The compound [78-1] obtained in the process (1) (4.9 g) was suspended in toluene (22 mL), and borane dimethyl sulfide complex (4.4 mL) was added at 0C, and then the reaction mixture was heated at reflux for 2 hours. The reaction mixture was cooled with ice-water bath, and an aqueous solution of 5N-sodium hydroxide (8 mL), an aqueous solution of 8N-sodium hydroxide (8 mL) and ethyl acetate (8 mL) were added, successively, and then the reaction mixture was stirred at room temperature for 2.5 hours. The reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL), and triethylamine (4.55 mL) and a solution of di-tert-butyl dicarbonate (6.2 g) in tetrahydrofuran (10 mL) were added successively at room temperature, and then a grain of dimethylaminopyridine was added, and the reaction mixture was stirred at room temperature for 22 hours. The reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (4.6 g) as a colorless oil. 1H-NMR (400 MHz, CDCl3) delta: 8. 03 (1H, s), 7. 07 (1H, dd, J = 7.9, 1.6 Hz), 6.96 (1H, d, J = 8.3Hz), 4.19-4.08 (1H, m), 3.57-3.43 (1H, m), 3.39-3.27 (1H, m), 1.53 (9H, brs), 1.30 (3H, d, J = 6.8 Hz). ESI-MS found: 256 [M-tBu+H]+

The synthetic route of 6-Bromo-3-methylindolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sato Pharmaceutical Co., Ltd.; NAGAI Keita; NAGASAWA Koh; TAKAHASHI Hirobumi; BABA Motoaki; FUJIOKA Shinichi; KONDOH Eri; TANAKA Kenichi; ITOH Yoshiki; EP2669270; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 50727-04-3, name is 5-Methoxyisoindoline-1,3-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. Quality Control of 5-Methoxyisoindoline-1,3-dione

A stirred solution of 4-methoxyphthalimide (21.3 g, 0.12 mol) in anhydrous tetrahydrofuran (425 ml) at 00C was treated dropwise with a solution of borane in tetrahydrofuran (1M1 340 ml, 0.34 mol) and the resulting mixture was stirred and held at reflux for 16 hours. The mixture was cooled to 00C, methanol (150 ml) was added dropwise followed by 5M hydrochloric acid (150 ml) and the mixture was stirred and held at reflux for 3 hours. Upon cooling to room temperature the organic solvent was removed in vacuo, the mixture was diluted with water (750 ml) and was extracted with dichloromethane (3 x 750 ml). The aqueous layer was basified to pH 12 or above by the addition of 5M sodium hydroxide, extracted with dichloromethane (3 x 750 ml) and the combined extracts were evaporated to dryness in vacuo to afford 5-methoxyisoindoline (8.34 g, 47%) as a brown oil. 1H NMR (DMSOd6) 7.13 (1 H1 d), 6.84 (1H, d), 6.74 (1H1 dd), 4.05 (2H, s), 4.01 (2H, s), 3.73 (3H, s). MS: [M+H]+ 150.

The synthetic route of 5-Methoxyisoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2008/44029; (2008); A1;,
Indoline – Wikipedia,
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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. 7147-90-2, name is 5-Chloroisoindoline-1,3-dione, A new synthetic method of this compound is introduced below., Product Details of 7147-90-2

To a solution of 5-chloro-isoindole-l,3-dione (3.63 g, 20 mmol) in DCM (150 mL) was added methylmagnesium chloride (3 M in THF, 20 mL) dropwise at 0 C. After the addition, the mixture was stirred at 0 C for 3 hours before it was quenched with satd. aq. NH4CI solution. After extraction with DCM, the organic layer was washed with brine, dried over anhy. Na2S04, filtered and concentrated in vacuo to give a crude product containing a mixture of two regioisomers (3.95 g, 100%). MS: 198.1 (M+H+).; Under N2 protection, triethylsilane (23 g, 200 mmol) and trifluoroboron etherate (8.51 g, 60 mmol) were added successively at -15 C to a mixture of 5-chloro-3-hydroxy-3-methyl- 2,3-dihydro-isoindol- 1 -one and 6-chloro-3-hydroxy-3-methyl-2,3-dihydro-isoindol- 1 -one (3.95 g, 20 mmol) in dry DCM (100 mL). Afterwards, the reaction mixture was stirred at room temperature for 2 hours and a saturated aqueous solution of NaHC03 (30 mL) was added. The mixture was then extracted with DCM and the organic layer was washed with brine, dried over anhy. Na2S04, filtered and concentrated in vacuo to give a crude mixture of products. The two regioisomers were separated by prep-HPLC to give the title compounds, 5-chloro-3-methyl-2,3-dihydro-isoindol-l-one (0.4 g, 11%) and 6-chloro-3- methyl-2,3-dihydro-isoindol-l-one (0.35 g, 9.6%) as white solids. MS: 182.0 (M+H+).

The synthetic route of 7147-90-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; AEBI, Johannes; AMREIN, Kurt; CHEN, Wenming; HORNSPERGER, Benoit; KUHN, Bernd; LIU, Yongfu; MAERKI, Hans P.; MAYWEG, Alexander V.; MOHR, Peter; TAN, Xuefei; WANG, Zhanguo; ZHOU, Mingwei; WO2013/79452; (2013); A1;,
Indoline – Wikipedia,
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Synthetic Route of 1074-82-4,Some common heterocyclic compound, 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, molecular formula is C8H4KNO2, 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 l-(bromomethyl)-4-methyl benzene (5 g, 27 mmol) in DMF (30 mL) was added potassium l,3-dioxoisoindolin-2-ide (7.51 g, 40.5 mmol) .The mixture was stirred at 100C for 14 hours. The reaction mixture was concentrated under reduced pressure to remove DMF. The residue was purified by column chromatography (S1O2, petroleum ethenethyl acetate = 0 to 20%) to give 2- (4-methylbenzyl)isoindoline-l,3-dione (5.50 g, 81% yield). XH NMR (chloroform-d 400 MHz) d 7.85 (d, (0925) J = 3.2 Hz, 2H), 7.84 (d, J = 3.2 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 4.82 (s, 2H), 2.32 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Potassium 1,3-dioxoisoindolin-2-ide, its application will become more common.

Reference:
Patent; H. LUNDBECK A/S; KEHLER, Jan; JUHL, Karsten; MARIGO, Mauro; VITAL, Paulo, Jorge, Vieira; JESSING, Mikkel; LANGGARD, Morten; RASMUSSEN, Lars, Kyhn; CLEMENTSON, Carl, Martin, Sebastian; (275 pag.)WO2019/115566; (2019); A1;,
Indoline – Wikipedia,
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