Category: indolines-derivatives

These common heterocyclic compound, 39755-95-8, name is 5-Methoxyisatin, 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. category: indolines-derivatives

General procedure: Fe 3 O 4 /COSbeta-CD-SO 3 H NPs (V) (0.02 g) were added to a mixture of isatin (1 mmol, 0.147 g), 5,5-dimethylcyclohexane-1,3-dione (dimedone) (1 mmol, 0.140g), and malononitrile (1mmol, 0.066g) in water (4mL). The mixture was magnetically stirred at 50C, for 20min. Reaction progress was monitored by TLC (n-hexane:EtOAc, 3:1). Upon reaction completion, the catalyst was removed by an external magnet, washed with water (10mL), and dried overnight to be ready for the next run. The formed solid was filtered off, washed with warm water, then dried to obtain pure products (0.328g, 98%).

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

Reference:
Article; Mohammadian, Narges; Akhlaghinia, Batool; Research on Chemical Intermediates; vol. 45; 10; (2019); p. 4737 – 4756;,
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Some common heterocyclic compound, 205383-87-5, name is tert-Butyl 2-oxospiro[indoline-3,3′-pyrrolidine]-1′-carboxylate, molecular formula is C16H20N2O3, 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. Safety of tert-Butyl 2-oxospiro[indoline-3,3′-pyrrolidine]-1′-carboxylate

A mixture containing commercially available tert-butyl 2-oxospiro [indoline-3, 3′-pyrrolidine] -1′-carboxylate (391 mg, 1.36 mmol) and NBS (290 mg, 1.63 mmol) in THF (5 mL) was heated to reflux and stirred for 20 h. The reaction mixture was then cooled, quenched with water, and extracted with EtOAc. The organic layer was concentrated and purified by chromatography on SiO2(2-20MeOH/DCM) to provide tert-butyl 5-bromo-2-oxospiro [indoline-3, 3′-pyrrolidine] -1′-carboxylate. MS (EI) calc’d for C16H20BrN2O3[M+H]+, 367 found, 367.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 205383-87-5, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; ACHAB, Abdelghani Abe; CHRISTOPHER, Matthew P.; FRADERA LLINAS, Francesc Xavier; KATZ, Jason D.; METHOT, Joey L.; ZHOU, Hua; XU, Shimin; FU, Jianmin; FU, Ning; LI, Yabin; WANG, Xichao; (228 pag.)WO2017/166104; (2017); A1;,
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Adding a certain compound to certain chemical reactions, such as: 1168150-46-6, name is (E)-Methyl 3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate, 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 1168150-46-6, Computed Properties of C18H15NO4

General procedure: A mixture of intermediate (3a, 3b, 6a, 6b, 10a, 10b, 11a-d, and14a-g, 1.5 mmol) and methyl (E)-3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate (1.5 mmol) in methanol (10 mL) wasstirred under reflux for 5-10 h. When TLC showed the completionof the reaction, the solution was cooled to room temperature. Theprecipitate was filtered off to give a crude product, which wasrecrystallized from methanol to provide the target compounds.

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, (E)-Methyl 3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang; European Journal of Medicinal Chemistry; vol. 139; (2017); p. 492 – 502;,
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Electric Literature of 496-12-8, 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.

A 1.0 g (8.4 mmol) amount of isoindoline was dissolved in 25 mL of acetonitrile. After addition of potassium carbonate (2.3 g, 16.8 mmol), the resulting mixture was heated at 70 C. After 30 min, the solution was allowed to cool to room temperature. A 4.2 mL (47.2 mmol) amount of 1-bromo-3-chloropropane was added and the reaction mixture stirred at room temperature for 24 h. The solvent was removed under reduced pressure and 60 mL water added to the residue. The product was extracted with 3¡Á30 mL dichloromethane. The combined organic fractions were washed with water and dried over sodium sulphate. The solvent was evaporated under reduced pressure. Purification by column chromatography (DCM:MeOH(NH3), 99:1 (v/v)) was performed and enabled collection of the product as a brown liquid (1.27 g, 77%). TLC: Rf 0.7 (DCM:MeOH(NH3), 9:1, v/v). 1H NMR (300MHz, CDCl3) delta: 7.21 (s, 4H, Haro); 3.95 (s, 4H, 2 CH2); 3.69 (t, 3J=7Hz, 2H, CH2); 2.90 (t, 3J=7Hz, 2H, CH2); 2.07 (p, 3J=7Hz, 2H, CH2). 13C NMR (75MHz, CDCl3) delta: 140.0 (2Caro); 126.7 (2Caro); 122.3 (2Caro); 59.1 (2CH2); 53.0 (CH2); 43.1 (CH2); 31.9 (CH2). LCMS (ESI+): Calc. for [M+H]: 196.05; 198.07. Found: 195.95; 197.91.

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:
Article; Donnier-Marechal, Marion; Carato, Pascal; Le Broc, Delphine; Furman, Christophe; Melnyk, Patricia; European Journal of Medicinal Chemistry; vol. 92; (2015); p. 575 – 582;,
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Electric Literature of 32692-19-6,Some common heterocyclic compound, 32692-19-6, name is 5-Nitroindoline, molecular formula is C8H8N2O2, 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.

We described the synthesis of the compound 1 (Table 2) to illustrate the general procedure for TFA accelerated Petasis three-component reaction. The descriptions of the preparations of all reported compounds are in the Supporting information section. To a magnetically stirred mixture of 5-nitroindoline (0.164 g, 1.0 mmol), 4-tolyboronic acid (0.135 g, 1.0 mmol), and glyoxylic acid monohydrate (0.092 g, 1.0 mmol) in CH2Cl2 (5 ml) was added TFA (20 mul). The mixture was stirred at room temperature for 4 h. After the completion of the reaction (TLC monitoring), half of the solvent was evaporated by means of a rotovap. The resulting solid was filtered through a sintered glass funnel. The collected solid was thoroughly washed with petroleum ether and a small amount of ice water (5 ml), and then dried in vacuo at room temperature for 24 h to afford 0.26 g (83.3 %) of 2-(5-nitroindolin-1-yl)-2-(p-tolyl) acetic acid as a light yellow solid. Mp: 177.0-178.1 C. 1H NMR (400 MHz, DMSO-d6): delta = 8.00 (1H, m), 7.86 (1H, s), 7.26 (4H, m), 6.70 (1H, d, J = 8.94 Hz), 5.71 (1H, s), 3.81 (1H, m), 3.21 (1H, m), 3.00 (2H, m), 2.32 (3H, s); 13C NMR (400 MHz, DMSO-d6): delta = 171.16, 156.59, 137.70, 137.38, 131.42, 130.49, 129.23, 128.83, 126.02, 120.28, 104.61, 61.16, 49.18, 26.15, 20.68 ppm. Calculated for C17H16N2O4, MS (ESI): m/z = 313.1181 (M+H)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Nitroindoline, its application will become more common.

Reference:
Article; Zhang, Jing; Yun, Fan; Xie, Rui; Cheng, Chunhui; Chen, Guangyao; Li, Jingxuan; Tang, Pingwah; Yuan, Qipeng; Tetrahedron Letters; vol. 57; 35; (2016); p. 3916 – 3919;,
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Application of 59-48-3, A common heterocyclic compound, 59-48-3, name is Indolin-2-one, molecular formula is C8H7NO, 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.

5-Nitro-2-oxindole 2-Oxindole (6.5 g) was dissolved in 25 mL concentrated sulfuric acid and the mixture maintained at -10 to -15 C. while 2.1 mL of fuming nitric acid was added dropwise. After the addition of the nitric acid the reaction mixture was stirred at 0 C. for 0.5 hr and poured into ice-water. The precipitate was collected by filtration, washed with water and crystallized from 50% acetic acid. The crystalline product was then filtered, washed with water and dried under vacuum to give 6.3 g (70%) of 5-nitro-2-oxindole.

The synthetic route of 59-48-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUGEN, Inc.; US2003/69421; (2003); A1;; ; Patent; Pharmacia Corporation; US2003/216410; (2003); A1;; ; Patent; Sugen, Inc.; US6051593; (2000); A;; ; Patent; Tang, Peng Cho; Miller, Todd A.; Li, Xiaoyuan; Sun, Li; Wei, Chung Chen; Shirazian, Shahrzad; Liang, Congxin; Vojkovsky, Tomas; Nematalla, Asaad S.; Hawley, Michael; US2002/156292; (2002); A1;,
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Synthetic Route of 480-91-1, The chemical industry reduces the impact on the environment during synthesis 480-91-1, name is Isoindolin-1-one, I believe this compound will play a more active role in future production and life.

Phthalimidine (800 mg, 6.01 mmol) was dissolved in THF(40 mL). At ambient temperature triethylamine (670 mg,6.62 mmol) was added dropwise and the mixture was stirred for5 min, whereupon dichlorophenylphosphine (538 mg, 3.01 mmol)was added and the mixture was stirred for one day. Thereafter thewhite precipitate was filtered and washed with THF (3 mL). Thecombined filtrate and washings were evaporated to dryness (condensationof volatiles into a cold trap under reduced pressure), theresidue was dissolved in THF (10 mL) and the solution was filteredthrough Celite. After vapor diffusion of n-pentane into the filtrate(for one week), white crystalline product suitable for single-crystalX-ray diffraction was obtained. The supernatant was removed bydecantation, the white solid was washed with n-pentane (3 mL)and dried in vacuo to yield 480 mg (1.29 mmol, 43%) of 1b.

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

Reference:
Article; Gericke, Robert; Wagler, Joerg; Polyhedron; vol. 125; (2017); p. 57 – 67;,
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Adding a certain compound to certain chemical reactions, such as: 41910-64-9, name is 4-Chloroindoline, 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 41910-64-9, name: 4-Chloroindoline

Example 28b Synthesis of 2-[2-(4-chloro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-methylmorpholin-4-yl)-3H-pyrimidin-4-one 0.975 g of the sodium salt of [4-(2-methylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid (example 1b, step 2b), 0.534 g of 4-chloroindoline, 0.57 ml of pyridine and 15 ml of DMF are placed in a round-bottomed flask, and then 0.9 g of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride is added. The reaction mixture is stirred at ambient temperature for 72 hours. The reaction mixture is poured into 50 ml of water, with stirring, and then the solid formed is filtered off through sintered glass and washed 3 times with approximately 15 ml of water, washed with 10 ml of EtOAc and rinsed with twice approximately 5 ml of diisopropyl ether, and the resulting product is left to air-dry under a hood. 2-[2-(4-Chloro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-methylmorpholin-4-yl)-3H-pyrimidin-4-one is isolated (0.98 g) and characterized in the form of an off-white solid (yield 71%).LCMS ES+DMSO Tr 1.15; MH+m/z=389Mass Spectrometry:The spectra were obtained on a Waters UPLC-SQD apparatusIonization: positive and/or negative mode electrospray (ES+/-)Chromatographic Conditions: Column: Acquity BEH C18-1.7 mum-2.1¡Á50 mm Solvents: A: H2O (0.1% formic acid) B: CH3CN (0.1% formic acid) Column temperature: 50 C. Flow rate: 1 ml/min Gradient (2 min): from 5 to 50% of B in 0.8 min; 1.2 min: 100% of B; 1.85 min: 100% of B; 1.95: 5% of BAnalytical Results:Retention time Tr (min)=0.82; [M+H]+: m/z 389; [M-H]-: m/z 3871H NMR spectrum (400 MHz): 1.06 (d, J=6.4 Hz, 3H); 2.48 (partially masked m, 1H); 2.80 (m, 1H); 3.19 (t, J=8.7 Hz, 2H); 3.40 to 3.50 (m, 2H); 3.76 (s, 2H); 3.81 (dd, J=3.0 and 11.5 Hz, 1H); 3.93 (m, 1H); 4.03 (m, 1H); 4.20 (t, J=8.7 Hz, 2H); 5.22 (s, 1H); 7.09 (d, J=8.1 Hz, 1H); 7.22 (t, J=8.1 Hz, 1H); 7.97 (d, J=8.1 Hz, 1H); 11.61 (broad s, 1H)

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, 4-Chloroindoline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SANOFI; Brollo, Maurice; Carry, Jean-Christophe; Certal, Victor; Didier, Eric; Doerflinger, Gilles; EL Ahmad, Youssef; Filoche-Romme, Bruno; Halley, Frank; Karlsson, Karl Andreas; Schio, Laurent; Thompson, Fabienne; US2013/274253; (2013); A1;,
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Application of 71294-07-0, These common heterocyclic compound, 71294-07-0, name is 5,6-Difluoroindolin-2-one, 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.

General procedure: To a 25 mL round bottomed flask was added different substituted oxindoles 8 (0.2 mmol, 1.0 equiv.) and bromoethylsulfonium salt 9 (132.99 mg, 0.3 mmol, 1.5 equiv.), DMF (2 mL). The mixture was stirred at room temperature for 5min and Et3N (61.88 mg, 0.6 mmol, 3.0 equiv.) was added into reaction system. The mixture was stirred for 6h at room temperature until the reaction completed, quenched with saturated ammonium chloride solution (5 mL), and was extracted with EtOAc (3¡Á30 mL). The combined organic layer washed with H2O (2¡Á10 mL), dried with anhydrous sodium sulfate. After concentration, product was purified using column chromatography on silica gel with suitable eluent.

The synthetic route of 71294-07-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Qin, Hui; Miao, Yuanyuan; Zhang, Ke; Xu, Jian; Sun, Haopeng; Liu, Wenyuan; Feng, Feng; Qu, Wei; Tetrahedron; vol. 74; 47; (2018); p. 6809 – 6814;,
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Synthetic Route of 5181-35-1, 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. 5181-35-1, name is 2-(2-Bromoethoxy)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

To a mixture of 2-(2-bromoethoxy)isoindoline-l,3-dione (20 g, 74 mmol) and ethyl lH-tetrazol-5-ylacetate (11.55 g, 74 mmol) in DMF (100 ml) was added cesium carbonate (29 gm, 0.088 mol) in portion wise at 25-30 C under stirring. The stirring was continued for 16 hrs. The reaction mixture was filtered and the collected filtrate was slowly poured onto chilled water (700 ml) under stirring. The formed precipitates of compound were filtered on Buchner funnel and washed with water (70 ml). The solid compound was dried at 40C for 2 hour under reduced pressure to yield crude compound 18.0 g. The crude compound was column purified using hexane and acetone. The non-polar spot isolated at 10-15% concentration of acetone in hexane and yielded 8.0 g of ethyl (2-{2-[(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)oxy]ethyl}-2H- tetrazol-5-yl)acetate. The polar spot isolated at 20-25% concentration of acetone in hexane, and the pure fractions were collected and concentrated on rota evaporator which yielded 5.0 g of ethyl (1- {2-[(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)oxy]ethyl}-lH-tetrazol-5-yl)acetate as white solid in 53% yield. Analysis: Mass: 346.3 (M+H); for Molecular weight: 345 and Molecular formula: C15H15N5O5. 1HNMR (CDCI3): delta 7.84-7.26 (m, 4H), 5.05 (t, 2H, J=5.2 Hz), 4.77 (t, 2H, J=5.6 Hz), 4.23-4.18 (q, 2H), 3.97 (s, 2H), 1.27 (t, 3H, J= 7.2 Hz).

The chemical industry reduces the impact on the environment during synthesis 2-(2-Bromoethoxy)isoindoline-1,3-dione. I believe this compound will play a more active role in future production and life.

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;,
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