Category: 496-12-8

Reference of 496-12-8, 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. 496-12-8, name is Isoindoline belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: In an oven-dried RB flask, 4-chloro-2-phenyl-1H-pyrrolo[3,2-c]pyridine 6b (250 mg, 1.09 mmol) and formaldehyde solution, 37 wt.% in H2O (0.2 mL, 2.73 mmol) were mixed in glacial acetic acid(5 mL). N-methyl piperazine (273.8 mg, 2.73 mmol, CAS 109-01-3)was added drop wise at 0C. The resulting mixture was stirred atroom temperature for 12 h. After completion of the reaction, the excess solvent was evaporated to dryness under reduced pressure.The residue was neutralized with 10% NaHCO3 solution, the solidf ormed was collected by filtration, washed with water and dried.The crude product was purified by silica gel column chromatographyto provide title compound as an off-white solid (326.3 mg,88%).

The synthetic route of Isoindoline has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jose, Gilish; Suresha Kumara, Tholappanavara H.; Sowmya, Haliwana B.V.; Sriram, Dharmarajan; Guru Row, Tayur N.; Hosamani, Amar A.; More, Sunil S.; Janardhan, Bhavya; Harish; Telkar, Sandeep; Ravikumar, Yalegara Siddappa; European Journal of Medicinal Chemistry; vol. 131; (2017); p. 275 – 288;,
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.

General procedure: j0444] A flame-dried 50-mE round-bottomed flask, equipped with a Teflon stir bar, was charged with 2-substituted N-aryl pyrrolidine (1 mmol, 1 equiv.), and degassed CH2C12:H20 (1:1, 25-mE). Then, sodium periodate (641.7 mg, 3.0 mmol, 3.0 equiv.) was added to the phenol solutionand the reaction was stirred for 4 h. Then, the reaction mixture was quenched by the addition of NaHSO4 (10 mE, 10% by weight aqueous solution), and the phases were separated, and the aqueous phase was washed with CH2C12 (3×20 mE). The organic fraction was dried over Mg504, filtered and concentrated in vacuo to afford a crude residue, which was purified using flash column chromatography (silica gel with 15% EtOAc in hexanes as eluant) to afford a white powder in 95% isolated yield.

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:
Patent; THE ROYAL INSTITUTION FOR THE ADVANCEMENT OF LEARNING/MCGILL UNIVERSITY; LUMB, JEAN-PHILIP; ESGUERRA, KENNETH V.N.; (118 pag.)US2017/66711; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

496-12-8, name is Isoindoline, 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. SDS of cas: 496-12-8

To a suspension of 2-[4-(2-bromoethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.50 g, 1.15 mmol) in anhydrous DMF (9 mL) was added isoindoline (0.41 mL, 3.46 mmol) and the reaction mixture was stirred at room temperature for 16 hours under nitrogen. The solvent was removed under reduced pressure and the residue was triturated with water (50 mL). The separated solid was filtered, washed with water and ether, and dried under vacuum to give the title compound as a white solid. Yield: 0.45 g (83%). MP 202-202.5 C. 1H NMR (400 MHz, CDCl3): delta 10.09 (br s, 1H), 7.77 (s, 2H), 7.22 (br s, 4H), 6.83 (d, J=2.4 Hz, 1H), 6.46 (d, J=2.4 Hz, 1H), 4.11 (s, 4H), 4.03 (t, J=6.0 Hz, 2H), 3.96 (s, 3H), 3.93 (s, 3H), 3.22 (t, J=6.0 Hz, 2H), 2.42 (s, 6H)

The synthetic route of 496-12-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RVX Therapeutics Inc.; McLure, Kevin G.; Young, Peter R.; US2013/281399; (2013); 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. 496-12-8, name is Isoindoline, A new synthetic method of this compound is introduced below., Safety of Isoindoline

General procedure: To a mixture of tert-butyl-3-bromopropylcarbamate 1.2 (5.6mmol, 1.3 eq, 1.3g) and N,N-disubstituted amine (4.3mmol, 1 eq) in 30mL of DMF was added potassium carbonate (13.0mmol, 3 eq, 1.8g). The resulting mixture was heated at 70C for 24h. Then, the solvent was removed under reduced pressure and water (80mL) added to the residue. The crude product was extracted with 3×60mL of DCM. The combined organic fractions were washed with 60mL of water and dried over magnesium sulphate. The solvent was evaporated and the crude product collected as yellow oil. Purification by column chromatography (DCM: MeOH(NH3), 9.7:0.3 (v/v)) was performed.

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; Donnier-Marechal, Marion; Carato, Pascal; Larchanche, Paul-Emmanuel; Ravez, Severine; Boulahjar, Rajaa; Barczyk, Amelie; Oxombre, Benedicte; Vermersch, Patrick; Melnyk, Patricia; European Journal of Medicinal Chemistry; vol. 138; (2017); p. 964 – 978;,
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

Related Products of 496-12-8, 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. 496-12-8, name is Isoindoline, This compound has unique chemical properties. The synthetic route is as follows.

Alternatively the amino compounds of the present invention can be synthesized applying Weinreb-rype chemistry (Tetrahedron Letters 2000, 41(8): 1141). As an example, the commercially available isoindoline 2 can be coupled to a commercially available N-protected amino ester (e.g., N-(diphenylmethylene)glycine ethyl ester ) 5 to form the amide 6 by first treating the amine 2 with an organo aluminum species such as trimethyl aluminum and adding the resulting organometallic intermediate to the protected amino ester 5 in an appropriate solvent such as DCM. Treatment of 6 with benzylbromide in the presence of a phase transfer catalyst (e.g., tetrabutylammonium bromide, TBAB) and a suitable base (e.g., potassium hydroxide, KOH) and a solvent such as DCM yields 7, (Journal of the American Chemical Society, 1989, 111(6):2353), which upon treatment with an acid (e.g., HCl) in a suitable solvent such as DCM produces 8, a compound of the present invention; To a solution of isoindoline (690 mg, 5.79 mmol) in DCM (5 ml) is added a 2M solution of trimethyl aluminum in heptane (2.9 ml, 5.79 mmol) and the resulting solution is allowed to stir at ambient temperature for 30 minutes. To this solution is added a solution of (benzhydrylidene-amino)-acetic acid ethyl ester (1.29 g, 4.82 mmol) in DCM (5 ml). The reaction is allowed to stir at ambient temperature for 18 h and carefully quenched with a 10% aqueous solution of citric acid. The resulting biphasic mixture is diluted with DCM (10 ml) and extracted with a saturated solution of Rochelle’s Salt (10 ml). The organic layer is separated, concentrated in vacuo and purified by column chromatography (hexanes-ethyl acetate 7-70%) resulting in 2- (Benzhydrylidene-amino)-l-(l,3-dihydro-isoindol-2-yl)-ethanone (1.0 g, 61%). 2-(Benzhydrylidene- amino)-l-(l,3-dihydro-isoindol-2-yl)-ethanone is analyzed by HPLC/Mass Spec.

The chemical industry reduces the impact on the environment during synthesis Isoindoline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2007/38459; (2007); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 496-12-8, name is Isoindoline, 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 496-12-8, name: Isoindoline

Example 137:; EPO 137To a dichloromethane solution (8 ml.) of phosgene (769 uL, 20% in toluene, 1.45 mmol) at -70C was added triethylamine (234 mg, 2.32 mmol) and isoindoline (138 mg, 1.16 mmol). The mixture was slowly warmed to room temperature and stirred for 1 hour. To the reaction mixture were added 103d (245 mg, 0.980 mmol), triethylamine (147 mg, 1.45 mmol) and 4-(dimethylamino)pyridine (18 mg, 0.15 mmol). The mixture was stirred at room temperature for 72h. It was then diluted with ethyl acetate (30 ml_) and washed with cold 1 M HCI (20 ml_), cold 1 M sodium bicarbonate (20 mL) and brine (20 mL), dried with Na2SO4 and concentrated. After column chromatography (20-40% ethyl acetate in hexane), the title compound was obtained in 57% yield. 1H NMR (CDCI3): delta 7.44 (1H, dd, J=8.6, 5.3Hz), 7.4-7.2 (4H, m), 7.03 (1 H, dd, J=9.8, 2.2Hz), 6.86 (1 H, m), 4.98 (1 H, m), 4.71 (4H, m), 4.25 (2H, m), 3.37 (2H, m), 1.28 (3H, t, J=7Hz). LCMS (APCI): 396.1 (M+H+).

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; PFIZER, INC.; WO2006/40646; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 496-12-8, These common heterocyclic compound, 496-12-8, name is Isoindoline, 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.

Example 343 (BVT074103); 2-anilino-5-[2-(1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-1, 3-thiazol-4 (5H)-one ;(2-anilino-4-oxo-4, 5-dihydro-1, 3-thiazol-5-yl) acetic acid (25 mg, 1 eq) was dissolved in DCM (1 mL) and 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (EDC, 29 mg, 1.5 eq), 1-hydroxybenzotriazole hydrate (HOBt, 20 mg, 1.5 eq), and N- methylmorpholine (NMM, 44 u. L, 4 eq) were added sequentially. After 10 min stirring at room temperature isoindoline (13 pL, 1.1 eq) was added and the reaction mixture was stirred overnight at room temperature H,, O (5 mL) and DCM (5 mL) was added, the organic layer separated on a 1-PS syringe and concentrated. Purified by flashtube DCM- MeOH (14: 1). 17 mg, yield 47%. 1H NMR (400 MHz, CHLOROFORM-D) 8 ppm 2.09-2. 45 (m, 2 H), 4.19-4. 42 (m, 1 H), 4.53-4. 77 (m, 4 H), 7.01-7. 22 (m, 7 H), 7.30-7. 42 (m, 2 H). MS [M+H] + m/z = 352.

Statistics shows that Isoindoline is playing an increasingly important role. we look forward to future research findings about 496-12-8.

Reference:
Patent; BIOVITRUM AB; WO2005/75471; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 496-12-8, name is Isoindoline, 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. Computed Properties of C8H9N

Intermediate 5A 2-(4-bromo-3-fluorophenyl)-1-(isoindolin-2-yl)ethanone [0492] [0493] To a mixture of 2-(4-bromo-3-fluorophenyl)acetic acid (300 mg, 1.287 mmol), isoindoline (0.161 mL, 1.416 mmol), and HATU (734 mg, 1.931 mmol) in DMF (5 mL), was add DIEA (0.450 mL, 2.6 mmol). The mixture was stirred rt for 18 h. The reaction mixture was diluted with EtOAc, then was washed with H2O, 1N HCl, H2O, sat. Na2CO3 and brine. The organic phase was dried (Na2SO4), filtered through a 1? pad of SiO2 and concentrated. The crude product was purified by flash chromatography (gradient from 0 to 100% ethyl acetate/hexanes) to afford 379 mg (88%) of Intermediate 5A as an off-white solid. MS (ESI) m/z: 333.9 (M+H)+; 1H NMR (400 MHz, CDCl3) delta 7.50 (dd, J=8.0, 7.4 Hz, 1H), 7.33-7.22 (m, 4H), 7.14 (dd, J=9.2, 2.0 Hz, 1H), 7.01 (dd, J=8.5, 1.9 Hz, 1H), 4.83 (s, 4H), 3.72 (s, 2H)

The synthetic route of Isoindoline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Glunz, Peter W.; Zou, Yan; Quan, Mimi L.; US2014/206686; (2014); 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. 496-12-8, name is Isoindoline, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: Isoindoline

To the suspension of isoindoline (2 g, 16.8 mmol) in 98% H2SO4 (10 mL) was added dropwise the mixture of concentrated nitric acid (2 mL) and 98% sulfuric acid (2 mL) at 0C. The mixture was stirred at 0C for 45 minutes. The resulting yellow solution was then poured into ice water. The white solid precipitate was collected by filtration. The solid was washed with water (20 mL x 2) and dried in vacuum to afford 231a as a white solid (700 mg, 51%). MS: [M+H]+ 165.

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; GILEAD CONNECTICUT, INC.; GENENTECH, INC.; BARBOSA, Antonio, J., M.; BLOMGREN, Peter, A.; CURRIE, Kevin, S.; KRISHNAMOORTHY, Ravi; KROPF, Jeffrey, E.; LEE, Seung H.; MITCHELL, Scott A.; ORTWINE, Daniel; SCHMITT, Aaron, C.; WANG, Xiaojing; XU, Jianjun; YOUNG, Wendy; ZHANG, Honglu; ZHAO, Zhongdong; ZHICHKIN, Pavel E.; WO2011/140488; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem