Indolines-derivatives

Synthetic Route of 118289-55-7, A common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, molecular formula is C10H9Cl2NO, 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 2; The mixture of methylene chloride (130 ml) and 1-(1,2-Benzisothiazol-3- yl)piperazine (9.5 gm) is stirred for 10 minutes, triethylamine (17 ml) is added drop wise for 15 minutes at 25 – 300C and then tetrabutyl ammonium bromide (4 gm) is added. Then trimethylsilyl chloride (9.5 ml) is added to the contents drop EPO wise for 20 minutes and stirred for 1 hour. The reaction mass is heated to 400C and methylene chloride is distilled off under vacuum. Then the reaction mass is cooled to 300C, dimethylformamide (75 ml) is added and stirred for 15 minutes. The reaction mass is filtered on hi-flo and washed with 50 ml of dimethyl formamide.The mixture of 5-(2-Chloroethyl)-6-chloro-oxindole (10 gm), water (25 ml), dimethyl formamide (35 ml) and sodium carbonate (10 gm) is heated to 1100C and to this mixture, above filtrate is slowly added drop wise at same temperature for 30 minutes. Then the reaction mass is stirred until completion of the reaction and then cooled to 300C. The reaction mass is added to chilled water (500 ml) and stirred for 20 minutes. The solid is filtered, slurried in isopropyl alcohol (200 ml). Then the solid is filtered, washed with isopropyl alcohol (100 ml), the solid is again slurried in isopropyl alcohol at reflux and refluxed for 1 hour. Then resulting solid is filtered at reflux point and washed with isopropyl alcohol (60 ml) to give 10 gm of ziprasidone (HPLC purity: 99.05%)..

The synthetic route of 118289-55-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; HETERO DRUGS LIMITED; WO2006/80025; (2006); 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. 7477-63-6, name is 7-Chloroisatin, A new synthetic method of this compound is introduced below., Product Details of 7477-63-6

General procedure: For compound 3, arenesulfenyl chloride (5 mmol) was added dropwise to a solution of isatin or isatin derivatives (5 mmol) and triethylamine (5 mmol) in N,N-dimethylformamide (DMF, 5 mL) at room temperature. Stirring was continued for an additional 30 min and then the mixture was poured into ice water (20 mL). The yellow precipitates were collected by filtration and recrystallized from ethanol to give pure 3a-3m.

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; Shang, Jian-Li; Guo, Hui; Li, Zai-Shun; Ren, Biao; Li, Zheng-Ming; Dai, Huan-Qin; Zhang, Li-Xin; Wang, Jian-Guo; Bioorganic and Medicinal Chemistry Letters; vol. 23; 3; (2013); p. 724 – 727;,
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. 39755-95-8, name is 5-Methoxyisatin, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 5-Methoxyisatin

General procedure: A mixture of isatin derivatves (1 mmole), malononitrile (1 mmole),1,3-dicarbonyl compounds (1 mmole), and Fe3+-mont. (0.05 g) in CH3CN(5 mL) was heated using an Elmasonic S 40 H ultrasonic cleaning unit at 50 C under silent condition. The progress of the reaction was monitored by TLC (EtOAc/hexane 3:7). After completion of the reaction, the catalyst was removed by filtration. Water was added to the residue. The solid which was obtained was filtered off and dried to provide pure products of the spirooxindole derivatives (4a-j) (Table 3).

According to the analysis of related databases, 39755-95-8, the application of this compound in the production field has become more and more popular.

Reference:
Article; Mamaghani, Manouchehr; Tabatabaeian, Khalil; Pourshiva, Mina; Nia, Roghayeh Hossein; Journal of Chemical Research; vol. 39; 6; (2015); p. 314 – 317;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 15861-23-1, 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. 15861-23-1 name is Indoline-5-carbonitrile, 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.

The 5 – cyano – indoline (0.14 g, 1. 00 mmol) is added to dichloromethane (6 ml) in, adding pyridine (0.24 g, 3. 00 mmol) and intermediate 6 a (0.27 g, 1.000 mmol), Canada finishes after stirring at room temperature 1 hour. Concentrated under reduced pressure the crude intermediate 6 b directly used for the next step reaction.

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

Reference:
Patent; Chengdu Xiandao Pharmaceutical Development Co., Ltd.; Li Jin; Wang Wei; Chu Hongzhu; Lv Kaizhi; Liu Lichuan; Nong Yunhong; Chen Wei; (17 pag.)CN110256416; (2019); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem