Category: indolines-derivatives

337536-15-9, name is 4-Bromoisoindolin-1-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. name: 4-Bromoisoindolin-1-one

General procedure: Example 1 4-[1-(3-chloro-4-fluorophenyl)-5-(3-chloro-5-fluorophenyl)-1H-pyrazole-3-yl]-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-1-one Step 4 [0522] 100 mg (0.25 mmol) of the product from step 3 is dissolved in 5 ml of dioxane and mixed with 75 mg (0.30 mmol) bis-pinakolato-diboron, 73 mg (0.74 mmol) potassium acetate and 12 mg (0.02 mmol) [1,1-bis-(diphenylphosphino)ferrocene]-dichloropalladium dichlormethane complex. The reaction mixture is stirred for 1 hour in the microwave at 120 C., cooled down to RT, mixed with 63 mg (0.37 mmol) of the compound from example 22A, 0.25 ml sodium carbonate solution (2 N in water, 0.50 mmol) and 10 mg (0.01 mmol) [1,1-bis-(diphenylphosphino)ferrocene]-dichloropalladium-dichlormethane complex and mixed for 2 hours at 120 C. The reaction mixture is filtered through a Millipore syringe filter, mixed with DMSO, and separated twice using preparative HPLC (solvent: acetonitrile/water gradient). This produces 42 mg (37% of theoretical yield) of the title compound. Example 3 4-[1-(3-chloro-4-fluorophenyl)-5-(3-chloro-5-fluorophenyl)-1H-pyrazole-3-yl]-2,3-dihydro-1H-isoindole-1-one [0533] [0534] The synthesis of the title compound is performed starting from 100 mg (0.25 mmol) of the product from step 3 of example 1 in a manner analogous to the synthesis of the compound from example 1. In step 4, instead of the compound from example 22A, 4-bromo-2,3-dihydroisoindol-1-on (63 mg, 0.30 mmol) is used. The result is 74 mg (65% of theoretical yield) of the title compound. [0535] 1H-NMR (400 MHz, DMSO-d6): delta=4.72 (s, 2H), 7.21 (dt, 1H), 7.32-7.41 (m, 2H), 7.49 (s, 1H), 7.51-7.58 (m, 2H), 7.62 (t, 1H), 7.71 (d, 1H), 7.83 (dd, 1H). [0536] LC-MS (Method 1): Rt=1.28 min; MS (ESIpos): m/z=456 [M+H]+.

The synthetic route of 337536-15-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AICURIS GMBH & CO. KG; Wildum, Steffen; Klenke, Burkhard; Wendt, Astrid; US2015/203500; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 496-12-8,Some common heterocyclic compound, 496-12-8, name is Isoindoline, molecular formula is C8H9N, 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 stirred solution of Boc-2,4-dichloro-d-phenylalanine (0.280 g, 0.84 mmol), EDC¡¤HCl (0.161 g, 0.84 mmol), HOBt (0.170 g, 1.26 mmol) and DIPEA (1.12 mL, 6.29 mmol) in DMF (2.0 mL), isoindoline (0. 10 g, 0.84 mmol) was added. The reaction was stirred at room temperature for 24 h. Upon completion, solvent was removed under reduced pressure and the crude was purified using column chromatography to provide desired coupled product in 78% yield. To the purified compound (0.21 g, 0.48 mmol) was added 1 M HCl (9.5 mL, 1 M in Et2O). After 4 h of stirring, the solvent was removed under reduced pressure to afford target compound 4 as a white solid. 1H NMR (400 MHz, CD3OD): delta 3.42 (d, 2H, 8.0 Hz), 4.24 (d, 1H, 12 Hz), 4.63 (t, 1H, 8.0 Hz), 4.72 (d, 1H, 16 Hz), 4.89 (d, 1H, 16 Hz), 5.00 (d, 1H, 12 Hz), 7.26 (m, 1H), 7.35 (m, 4H), 7.44 (d, 1H, 8.0 Hz), 7.54 (d, 1H, 4.0 Hz) 13C NMR (100.6 MHz, CD3OD): delta 35.3, 52.1, 53.2, 53.6, 123.7, 123.9, 128.9, 129.1, 129.2, 130.7, 132.1, 132.4, 136.0, 136.3, 136.4, 136.6, 168.1 HRMS (TOF-MS) Exact mass calcd for C17H16Cl2N2O [M+H]+: 335.0718, found: 335.0712.

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

Reference:
Article; Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko; Zhu, Yanyi; Atadja, Peter W.; Claiborne, Tavina; Grob, Jonathan E.; McRiner, Andrew; Pancost, Margaret R.; Patnaik, Anup; Shao, Wenlin; Shultz, Michael; Tichkule, Ritesh; Tommasi, Ruben A.; Vash, Brian; Wang, Ping; Stams, Travis; Bioorganic and Medicinal Chemistry; vol. 19; 15; (2011); p. 4626 – 4634;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 954-81-4,Some common heterocyclic compound, 954-81-4, name is N-(5-Bromopentyl)phthalimide, molecular formula is C13H14BrNO2, 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: Procedure M1. A mixture of the appropriate 2-(bromoalkyl)isoindoline-1,3-dione (1 equiv) with amine (pyrrolidine or morpholine) (1.1 equiv) in the presence of K2CO3 (3 equiv) was stirred in acetonitrile under reflux for 20 h. Subsequently, the solvent was evaporated under reduced pressure,producing a residue which was further dissolved in 20 mL of water and extracted with DCM(3 x 30 mL). The organic layer was dried with anhydrous Na2SO4. The solvent was then evaporated and the residue was purified by silica gel column chromatography (S3) yielding a yellow oil. The finalproduct was transformed into hydrochloride salt. The following compounds were obtained.

The synthetic route of 954-81-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Hebda, Michalina; Bajda, Marek; Wieckowska, Anna; Szal?aj, Natalia; Pasieka, Anna; Panek, Dawid; Gody?, Justyna; Wichur, Tomasz; Knez, Damijan; Gobec, Stanislav; Malawska, Barbara; Molecules; vol. 21; 4; (2016);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 64483-69-8, 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. 64483-69-8, name is 5-Acetylindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE II 1.5-diacetyl-2-indolinone 48.9 g (0.279 mol) 5-acetyl-2-indolinone are stirred in 400 ml acetic anhydride in an oil bath at 140 C. for 2 h. During this time the starting material dissolves. Then the reaction mixture is left to cool, evaporated down, the precipitate is removed by suction filtering, washed with ether and the product is dried. Yield: 56.0 g (92.4% of theory) Rf=0.41 (silica gel, methylene chloride/methanol 50:1) C12H11NO3 (MW=217.223) Mass spectrum: m/z=216 (M-H)-

The synthetic route of 5-Acetylindolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Boehringer Ingelheim International GmbH; US2005/234120; (2005); A1;,
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. 22190-33-6, name is 5-Bromoindoline, This compound has unique chemical properties. The synthetic route is as follows., Safety of 5-Bromoindoline

EXAMPLE 489A tert-butyl 5-bromoindoline-1-carboxylate A suspension of 5-bromo-2,3-dihydro-1H-indole (1.0 g, 5.05 mmol) in diethyl ether (50 mL) was treated with di-tert-butyl-dicarbonate (1.32 g, 6.05 mmol), stirred overnight at room temperature and filtered. The filtrate was diluted with hexanes and concentrated in vacuo until crystal formed. The crystals were collected via filtration to give 1.05 g (70% yield) of the desired product. 1H NMR (300 MHz, DMSO-D6) delta ppm 1.50 (s, 9H), 3.06 (t, J=8.82 Hz, 2H), 3.90 (m, 2H), 7.30 (dd, J=8.48, 2.03 Hz, 1H), 7.37 (m, 1H), 7.56 (s, 1H).

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 22190-33-6.

Reference:
Patent; Betschmann, Patrick; Burchat, Andrew F.; Calderwood, David J.; Curtin, Michael L.; Davidsen, Steven K.; Davis, Heather M.; Frey, Robin R.; Heyman, Howard R.; Hirst, Gavin C.; Hrnciar, Peter; Michaelides, Michael R.; Muckey, Melanie A.; Rafferty, Paul; Wada, Carol K.; US2005/26944; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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.

To a 2000 ml 4 neck RBF, charge Isopropanol (1000 ml), Methyl amine 33% solution in methanol (1000 ml) and 100 gms compound (III). Stirr the reaction mass at 55-60C for 5 hrs. Cool the reaction mass at 25-30C and stirr for 1 hr. Filter the reaction mass and wash with Isopropanol (50 ml). Dry the solid at 45-50C under vacuum. Dry Wt: 55 gms (Theoretical yield: 79.60%); Purity: 97.70%

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; MEHTA API PVT. LTD.; KHAN, Rao, Uwais, Ahmad; SONI, Amit Manohar; MALI, Sanjay, Gunda; (29 pag.)WO2016/199027; (2016); A1;,
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. 446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Formula: C22H19N3O6

S5, At room temperature 2-[[(S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidine-5-yl]methyl]- 1H-isoindole-1,3(2H)-dione(69.9 g, 0.165 mol) Obtained in step S4 was added to ethanol (1 L),80% hydrazine hydrate (0.044 g, 0.908 mmol) was added dropwise, and the mixture was heated to reflux for 2 h, then cooled to room temperature. The solvent was evaporated under reduced pressure. Water (1L) was evaporated. It was dried over anhydrous sodium sulfate, suction filtered, and then evaporated.The obtained residue was dried under reduced pressure to give a white solid(50.5g, 95.6%); Mp 149 ~ 152 C, [alpha]D25-42.6(c 0.1,DMSO) Chiral purity was 99.9% (HPLC normalization).

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 446292-08-6.

Reference:
Patent; Suzhou Zhonglian Chemical Pharmaceutical Co., Ltd.; Zhou Zijin; Chen Feng; Luo Xinzu; Huang Junhao; (10 pag.)CN108690010; (2018); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 3416-57-7,Some common heterocyclic compound, 3416-57-7, name is 2-(2-Oxopropyl)isoindoline-1,3-dione, molecular formula is C11H9NO3, 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.

2.0g of compound I is mixed with 3.76g of potassium carbonate thoroughly, then the resulting mixture is poured into a 25ml flask followed by adding 4.0ml of chloroacetone into, heating the solution to 90-110C (a reflux condensing tube is needed to be equipped on the flask, the system is protected with argon) while stirring, maintaining the temperature, and conducting the reaction for 3-4 hours. After the reaction is completed, excess chloroacetone is removed under a reduced pressure, into the residue is added a great deal of water, then filtrated with Buchner’s filter. The resulting solid is washed twice with 10ml of 10% NaOH and 5-6 times with water respectively, dried under vacuum to obtain compound II; After a reflux condensing tube and a dropping funnel are connected on a three-necked bottle, 100ml of absolute methanol (or other anhydrous solvent) is added into the three-necked bottle, followed by slowly adding 0.23g of metallic sodium (or directly adding 10mmol of sodium methoxide). After the solid dissolves entirely, the solution is heated and refluxed, then compound II dissolved in absolute methanol (60ml CH3OH and 1.0g compound II) is dropped into by dropping funnel. After conducting the reflux for 2 hours the reaction is processed as follows: cooling the system with icewater bath, slowly neutralizing the reaction solution with 1M hydrochloride, continuing to stir for 30min in icewater bath after a large amount of solid emerge, filtrating to obtain a solid, then washing the solid with small amount of water, drying in vacuum, thereby obtaining compound III. 230mg of compound III is placed in a 25ml flask followed by adding 5ml solvent (listed in the above) into, air is blown into by a bubbler continuously. The reaction is completed after 10 hours and processed as follows: diluting the reaction solution with 30ml of acetic ether, extracting with water, back-extracting the water phase with 30ml of acetic ether, washing the organic phases with water and saturated salt solution respectively, combining the organic phases, then drying, condensing, the residue is applied on silica gel column (petroleum ether: acetic ether=2:1) to obtain compound IV

The synthetic route of 3416-57-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Institute of Materia Medica, Chinese Academy of Sciences; EP1640367; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 954-81-4, These common heterocyclic compound, 954-81-4, name is N-(5-Bromopentyl)phthalimide, 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.

To a stirred solution of compound 14-k (80 g, 0.27 mol) in DMF (745 mL) was added potassium thioacetate (34 g, 0.29 mol) portion wise over 20 mm at room temperature .Afier complete addition, the reaction mixture was stirred at room temperature for 30 mm. Reaction progress was monitored by TLC; after completion the reaction mixture was quenched with ice-cold water (1 L) and stirred for I h. The resultant precipitate was filtered, washed with water (500 rnL) and dried in vacuo to afford 15-k as an off-white solid (75 g, 95%).?H NMR (40() MHz, C1)Ci3): d 7.84 (dd, J= 5.5 Hz, 3.() Hz, 2K), 7.71 (dd, j:zr. 5.5 Hz, 3.1 Hz, 2H), 3.67 (t, J= 7.3 Hz, 2H), 2.85 (t, J= 7.3 Hz, 2H), 2.30 (s, 3H), 1.73-1.65 (m, 3H), 1.64-1.57 (m, 1Ff), 1.46-1.37 (m, 2H);LC-MS: 292.2 (M+1).

The synthetic route of 954-81-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CV6 THERAPEUTICS (NI) LIMITED; SPYVEE, Mark; SHIRUDE, Pravin S.; (258 pag.)WO2017/6282; (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 337536-15-9 as follows. Computed Properties of C8H6BrNO

EXAMPLE 2A 4-bromo-7-nitro-1-isoindolinone A 0 C. solution of Example 1C (5 g, 23.6 mmol) in 10 mL sulfuric acid was treated with a solution of concentrated nitric acid (1.55 mL, 24.7 mmol) in 10 mL sulfuric acid via addition funnel. The resulting mixture was stirred at 0 C. for 1 hour, warmed to room temperature, stirred overnight, poured over ice, and filtered. The filter cake was washed with water and diethyl ether and then dried to give 5.39 g of the desired product. 1H NMR (300 MHz, DMSO-d6) delta 4.39 (s, 2H); 7.88 (d, J=8.1 Hz, 1H); 8.05 (d, J=8.5 Hz, 1H); 9.17 (s, 1H).

According to the analysis of related databases, 337536-15-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Curtin, Michael L.; Davidsen, Steven K.; Frey, Robin R.; Heyman, Howard R.; Holms, James H.; Michaelides, Michael; Steinman, Douglas H.; US2005/26976; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem