Category: indolines-derivatives

32692-19-6, name is 5-Nitroindoline, 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. Product Details of 32692-19-6

To a stirred solution of chlorosulfonyl isocyanate ( 3.67 g , 26 mmol) in DCM ( 5 ml ), t- butanol (2.07g , 28 mmol) was added dropwise at 0 C under nitrogen atmosphere and stirred for 15 min. This mixture was added to a solution of 5-Nitroindoline (3.7 g, 22 mmol) and TEA ( 6.66 g , 66 mmol) in DCM ( 50 ml ) at 0 C under nitrogen atmosphere and stirred at rt for 8 hr . Solvent was evaporated , water (30 ml ) was added to the residue & the yellow solid was filtered and dried (7.53 g , 90.24%). MS = m/z 343 [M-I].

The synthetic route of 32692-19-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LUPIN LIMITED; WO2009/109999; (2009); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 20870-90-0, 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. 20870-90-0 name is 5-Bromo-1-methyl-2-oxoindoline, 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.

To 5-bromo-1-methyl-1 ,3-diotahydro-iotandol-2-one (CASNo. 20870-90-0, 80 mg, 0 35 mmol) was added 5-methyl-3-pyndmyl boronic acid (CASNo. 173999-18-3 55 mg, 0 39 mmol), in 1 ,2-diotamethoxyethane (2 7 mL) and 2 M aqueous sodium carbonate (0 45 mL, 0 9 mmol) The reaction mixture was degassed and placed under an argon atmosphere, at which time resin bound tetrakiotas(triotaphenylphosphiotane)palladiotaum(0)( specifically polystyrene triphenytphosphine palladium (0) [PS-PPh3-Pd(O) (Biotage), 0 09 mmol/g loading (195 mg, 0 018 mmol)] was added The reaction vessel was sealed and was heated by microwave irradiation at 100 C for 1.5 hours The reaction mixture was cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane 0 to 6%) to afford 1-methyl-5-(5-methyl-pyridiotan-3-yl)-1 3- dihydro-iotandol-2-one, HRMS (ESI) m/z 239 1 181 (M+H)Phi, 1H NMR (400 MHz, CDCI3) delta ppm 2,42 (s, 3 H), 3 27 (s, 3 H), 3 61 (s, 2 H), 6 93 (d, J=8 1 Hz, 1 H) 7 45 – 7.58 (m, 2 H), 7 67 (S1 1 H), 8 42 (s, 1 H), 8.63 (s, 1 H)

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

Reference:
Patent; NOVARTIS AG; ADAMS, Christopher Michael; CHAMOIN, Sylvie; HU, Qi-Ying; ZHANG, Chun; WO2010/130794; (2010); 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 496-12-8 as follows. Application In Synthesis of Isoindoline

To a solution of 3,4-(methylenedioxy)aniline (150 mg, 1.09 mmol) in dry DCM (4 mL) was added dropwise phenyl chloroformate (0.138 ml, 1.09 mmol) and triethylamine (0.153 ml, 1.09 mmol). After the reaction mixture was stirred at r.t for 8 hr., isoindoline (0.123 ml, 1.09 mmol) and triethylamine (0.153 ml, 1.09 mmo) were added, and the reaction mixture was stirred overnight. The solvent was then removed under reduced pressure, and the residue was purified by chromatographed on silica gel (EtOAC/Hexane: 1:3) to give the title compound (185 mg, 60%) as a white solid: m.p:165-166 C. 1H NMR (CDCl3, 500 MHz): 4.82 (s, 4H); 5.93 (s, 2H); 6.20 (s, 1H); 6.73 (s, 2H); 7.17 (s, 1H); 7.30 (m, 4H). MS (MH+, 283).

According to the analysis of related databases, 496-12-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Tachdjian, Catherine; Patron, Andrew P.; Adamski-Werner, Sara L.; Bakir, Farid; Chen, Qing; Darmohusodo, Vincent; Hobson, Stephen Terrence; Li, Xiaodong; Qi, Ming; Rogers, Daniel Harry; Rinnova, Marketa; Servant, Guy; Tang, Xiao-Qing; Zoller, Mark; Wallace, David; Xing, Amy; Gubernator, Klaus; US2005/84506; (2005); 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. 6872-06-6, name is 2-Methylindoline, A new synthetic method of this compound is introduced below., Formula: C9H11N

Example 4Synthesis of 5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)sulfonyl)-1-((4-fluorophenyl)sulfonyl)-2-methylindolineReagents MW Mole Reagent/raw material (g/mole) Quantity moles ratio 2-methylindoline 161.20 177 mg 1.33 mmol 1 eq. 4-fluorobenzene-1- 194.61 235 mg 1.33 mmol 1.0 eq. sulfonyl chloride 1-((4-fluorophenyl)sulfo- 291.34 267 mg 0.88 mmol 1.0 eq. nyl)-2-methylindoline 2,3-dihydro- 234.66 206 mg 0.88 mmol 1.0 eq. benzo[b][1,4]dioxine- 6-sulfonyl chloride Aluminium chloride 133.3 147 mg 1.1 mmol 1.25 eq. Step I: 2-methylindoline was dissolved in 5 mL dry pyridine, and 4-methoxybenzene-1-sulfonyl chloride was dropped in 2 portions under N2. The reaction was stirred for 2 hours at room temperature and an intense red color developed. When the reaction was complete as determined by HPLC using the protocol described above, as well as by TLC (8/2 PE/EtOAC), the crude reaction mixture was poured into 100 mL cold 0.5M HCl, and extracted twice with 50 mL CH2Cl2. The organic phase was evaporated, and the evaporation residue was purified by passing through a silica plug (100 g silica gel in large sinter glass). The product eluted in 7/3 PE/EtOAC, while all of the pink polar byproduct was retained on silica. The organic phase was dried on Na2SO4, and then evaporated and used for the next step without further purification (Product 100% pure, 378 mg, yield 99%).

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; Becker, Oren M.; Shitrit, Alina; Schutz, Nili; Ben-Zeev, Efrat; Yacovan, Avihai; Ozeri, Rachel; Kehat, Tzofit; Mirilashvili, Sima; Aizikovich, Alex; Sherman, Daniel; Behar, Vered; Kashtan, Osnat; US2012/108631; (2012); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 5181-35-1, 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. 5181-35-1 name is 2-(2-Bromoethoxy)isoindoline-1,3-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.

To a solution of 2-(2-bromoethoxy) isoindoline-l,3-dione (10 g, 37 mmol) and tert-buty 2-(lH-tetrazol-5-yl)ethylcarbamate (7.88 g, 37 mmol) in dimethyl formamide (50 ml) was added cesium carbonate ((14.48 g, 44 mmole) in portion wise at 25-30 C under stirring. The reaction mixture was stirred for further 16 hours and filtered; the filtrate was slowly poured into chilled water (400 ml) under stirring and continued stirring for 30 minutes. The formed precipitates of compound were filtered and washed with water (40 ml). The solid compound was dried at 40C for 2 hour under high vacuum, yielded 12 g. The compound was column purified using hexane and acetone as an eluent. The mixture was isolated at 10-15% concentration of acetone in hexane to yield 10 g of 2-{2-[5-(2-tertiary butoxy carbonyl aminoethyl)-2H-tetrazol-2-yl]ethoxy}-lH-isoindole-l,3(2H)-dione and 2-{2-[5-(2-tertiary butoxy carbonyl aminoethyl)-lH-tetrazol-l-yl]ethoxy}-lH-isoindole-l,3(2H)-dione in 67% yield Analysis: Mass: 403 (M+l); for Molecular weight: 402 and Molecular formula: C18H22N6O5..; Hydrazine hydrate monohydrate (1.86 ml, 037.3 mmol) was added to a solution of 2-{2-[5-(2- tertiary-butoxy-carbonyl-aminoethyl)-2H-tetrazol-2-yl]ethoxy}-lH-isoindole-l,3(2H)-dione and 2- {2-[5-(2-tertiary-butoxy-carbonyl-aminoethyl)-lH-tetrazol-l-yl]ethoxy}-lH-isoindole-l,3(2H)- dione (10 g, 24.8 mmol, obtained from step 1) in dichloromethane (10 ml) under stirring at room temperature. After completion of 2 hours of stirring at same temperature the TLC confirms the completion of reaction. The reaction mass was filtered and the solid was washed with dichloromethane (50 ml). The collected filtrate was concentrated at 40C under vacuum to yield 6.75 g of the product, which was used further without any purification. Analysis: Mass: 273 (M+l); for Molecular weight: 272 and Molecular formula: CioH2oN603.

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

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

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. 868066-91-5, name is 5-Bromo-2-methylisoindolin-1-one, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 5-Bromo-2-methylisoindolin-1-one

Synthesis of 5-bromo-2,3-dimethylisoindolin-1-one (2) To a solution of 5-bromo-2-methylisoindolin-1-one (1, 1 g, 4.42 mmol) in tetrahydrofuran (20 mL) at -78° C., sodium hexamethyldisilazane (4.4 mL, 4.86 mmol 1M solution in tetrahydrofuran) was added and the reaction mixture was allowed to stir at the same temperature for 15 min. Methyl iodide (0.55 mL, 8.85 mmol) was added and the reaction mixture was stirred at -78° C. for 2 h. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, separated, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 30percent ethyl acetate in hexanes as eluent to afford 5-bromo-2,3-dimethylisoindolin-1-one (2). Yield: 0.1 g, 9percent; MS (ESI) m/z 240 [M+1]+.

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 868066-91-5.

Reference:
Patent; eFFECTOR Therapeutics, Inc.; Sprengeler, Paul A.; Reich, Siegfried H.; Ernst, Justin T.; Webber, Stephen E.; Shaghafi, Mike; Murphy, Douglas; Tran, Chinh; (131 pag.)US10112955; (2018); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 883-44-3, name is 2-(3-Hydroxypropyl)isoindoline-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. name: 2-(3-Hydroxypropyl)isoindoline-1,3-dione

(i) Preparation of trans and cis 2-(3,4,5-trimethoxyphenyl)-5-(3-phthalimidyl propoxy) tetrahydrofuran (compounds 107, 108) Compound 105 (1.14 g, 4.49 mmol) was dissolved in 4 mL dichloromethane. Triethylamine (681.4 mg, 6.73 mmol) was added to this solution. The reaction mixture was cooled with an ice bath and trifluoroacetic anhydride (1.41 g, 6.73 mmol) was added in a dropwise manner. The reaction mixture was stirred at 0 C. for 30 minutes and then 3-phthalimidylpropanol (106) (2.4 g, 13.26 mmol) was added. The reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours. The reaction was quenched with saturated aqueous NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with water and saturated NaCl solution, dried over MgSO4, filtered and evaporated in vacuo to an oil which was purified by column chromatography (silica, 2:1 hexane/ethyl acetate) (107: 522 mg (trans); 108: 271 mg (cis); 1:1 mixture of 107 and 108: 110 mg; total yield 46%). 1 H NMR (CDCl3): 107: 1.70 (m,1H); 1.82 (m,1H); 2.00(m,2H); 2.02(m,1H); 2.28(m,1H); 3.46(m,1H); 3.83(s,3H); 3.84(m,3H); 3.88(s,6H); 4.99(t,1H); 5.30(dd,1H); 6.56(s,2H); 7.72(m,2H); 7.85(m,2H). 108: 1.95(m,3H); 2.00(m,2H); 2.20(m,1H); 3.51(m,1H); 3.83(s,3H); 3.85(m,2H); 3.88(s,6H); 3.92(m,1H); 4.90(m,1H); 5.16(dd,1H); 6.60(s,2H); 7.72(m,2H); 7.84(m,2H).

The synthetic route of 2-(3-Hydroxypropyl)isoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Cytomed, Inc.; US5681966; (1997); A;,
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. 169037-23-4, name is 5-(Trifluoromethoxy)indoline-2,3-dione, A new synthetic method of this compound is introduced below., name: 5-(Trifluoromethoxy)indoline-2,3-dione

General procedure: A mixture of indoline-2,3-dione 1 (1mmol), l-tryptophan (2a) or l-histidine 2b (1mmol) and (E)-(2-nitrovinyl)benzene 3 (1.1mmol) was heated while stirred in [bmim]Br as the reaction medium (3mL) for 1hat 100C. After completion of the reaction (TLC), EtOAc (5mL) was added and the reaction mixture was stirred for 10min. This treatment was repeated and the combined ethyl acetate layers were removed in vacuo. The crude product was purified by recrystallization of the residue from EtOH (compounds 4) or by column chromatography (compounds 5). After extraction of the product, the ionic liquid was dried under vacuum at 80C for 2h to eliminate any water and could be reused for subsequent runs of the reaction.

The synthetic route of 169037-23-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Arumugam, Natarajan; Almansour, Abdulrahman I.; Kumar, Raju Suresh; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A.; Govindasami, Periyasami; Altaf, Mohammad; Menendez, J. Carlos; Tetrahedron; vol. 74; 38; (2018); p. 5358 – 5366;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

317-20-4, name is 7-Fluoroisatin, 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 7-Fluoroisatin

General procedure: In a 25 mL round bottom flask, isatins 1 (1 mmol), 3-phenylisoxazol-5(4H)-one 2 (1 mmol) or 3-ethylisoxazol-5(4H)-one 7 (1 mmol), pyrazol-5-amine 3 (1 mmol) or 6-aminopyrimidine-2,4-(1H,3H)-dione 5 (1 mmol), and Amberlyst-15 (100 mg) were stirred in CH3OH (5.0 mL) at 80 C. When the reaction was completed (detected by TLC), the spherical catalyst was separated by a sieve at once under hot condition. Then, the reaction mixture was cooled to room temperature, and solid precipitation occurred. After filtration, the crude product was recrystallized from EtOH and DMF to give pure compound.

The synthetic route of 317-20-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Niu, Qingqing; Xi, Junhua; Li, Lei; Li, Li; Pan, Chengli; Lan, Meijun; Rong, Liangce; Tetrahedron Letters; vol. 60; 43; (2019);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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, Computed Properties of 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%)

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; 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,
Indoline | C8H9N – PubChem