Author: Jessica.F

Some common heterocyclic compound, 59-48-3, name is Indolin-2-one, molecular formula is C8H7NO, 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. Quality Control of Indolin-2-one

An oven-dried 250 mL round-bottom flask containing indolin-2-one (5.00 g, 36.7 mmol) was fitted with a stirbar and septa, then flushed with nitrogen. Tetrahydrofuran (50 mL) was added and the mixture cooled to -78 . A solution of n-butyllithium in hexane (32.3 mL, 80.7 mmol, 2.5 M solution) was added, and the resulting solution was stirred at -78 for 30 minutes. Next, iodomethane (13.0 g, 91.8 mmol) was added and the mixture stirred at -78 for 10 minutes. The reaction solution was quenched with saturated aqueous ammonia hydrochloride solution. The resulting mixture was extracted with EtOAc (3 x 30 mL) and the combined organic layers were washed with brine (50 mL) , dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by chromatography on SiO2(0to 50EtOAc/petroleum ether) to afford 3-methylindolin-2-one. MS (EI) calc?d for C9H10NO [M+H]+, 148 found, 148.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 59-48-3, 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;,
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. 334952-09-9, name is 2-Oxoindoline-6-carboxylic acid, A new synthetic method of this compound is introduced below., name: 2-Oxoindoline-6-carboxylic acid

Example 31 COMPOUND IN-023 2-Oxo-3-[5-(2-pyrrolidin-1-yl-ethoxy)-1H-indol-2-ylmethylene]-2,3-dihydro-1H-indole-6-carboxylic acid 2-Oxo-2,3-dihydro-1H-indole-6-carboxylic acid was condensed with 5-(2-pyrrolidin-1-yl-ethoxy)-1H-indole-2-carbaldehyde to give the title compound. 1H-NMR (360 MHz, DMSO-d6) delta 12.86 (s, 1H, NH), 11.11 (br s, 1H, NH), 8.01 (s, 1H, H-vinyl), 7.78 (d, J=8 Hz, 1H), 7.64 (dd, J=1.5 & 8 Hz, 1H), 7.51 (d, J=9 Hz, 1H), 7.43 (d, 1H), 7.15 (d, J=2 Hz, 1H), 7.10 (s, 1H), 4.11 (t, J=6 Hz, 2H, CH2), 2.89 (t, J=6 Hz, 2H, CH2), 2.61 (m, 4H, 2*CH2), 1.71 (m, 4H, 2*CH2). MS-Ve APC1 m/z 416.5 [M+-1].

The synthetic route of 334952-09-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Tang, Peng Cho; Harris, G. Davis; Li, Xiaoyuan; US2002/52369; (2002); 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. 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal, A new synthetic method of this compound is introduced below., name: 3-(1,3-Dioxoisoindolin-2-yl)propanal

Example M9 N-(3-Aminopropyl)-N-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2-hydroxyacetamide 150.0 mg (0.42 mmol) of (1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropan-1-amine (Intermediate C52) were initially charged in 2.0 ml of dichloromethane, and 29.2 mg (0.49 mmol) of HOAc and 125.6 mg (0.59 mmol) of sodium triacetoxyborohydride were added and the mixture was stirred at RT for 5 min. 98.9 mg (0.49 mmol) of 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanal were added. The reaction mixture was stirred at RT overnight. The reaction mixture was diluted with ethyl acetate and the organic phase was washed twice with saturated sodium carbonate solution and once with saturated NaCl solution. After drying over magnesium sulphate, the solvent was evaporated under reduced pressure and the residue was purified on silica gel (eluent: dichloromethane/methanol 100:1). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 188.6 mg (74%) of the compound 2-[3-({(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino)propyl]-1H-isoindole-1,3(2H)-dione. LC-MS (Method 1): Rt=1.00 min; MS (ESIpos): m/z=541 [M+H]+.

The synthetic route of 2436-29-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; LERCHEN, Hans-Georg; REBSTOCK, Anne-Sophie; MARX, Leo; JOHANNES, Sarah Anna Liesa; STELTE-LUDWIG, Beatrix; DIETZ, Lisa; TERJUNG, Carsten; MAHLERT, Christoph; GREVEN, Simone; SOMMER, Anette; BERNDT, Sandra; (481 pag.)US2019/77752; (2019); 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 60434-13-1 as follows. SDS of cas: 60434-13-1

General procedure: To a flame-dried screw-capped test tube equipped with a magnetic stir bar was added I, 4,7,10,13, 16-hexaoxacyclooctadecane (0.396 g, 1.5 mmol), KF (0.087 g, 1.5 mmol) and 1- methylindoline-2,3-dione 3 (0.50 mmol). Then the screw-capped tube was evacuated and backfilled with argon. The mixture was dissolved in THF (2.0 mL) under argon atmosphere. The resultant reaction mixture was kept stirring at 30 C for 5 min. To the stirring solution was added pyridine 7 (0.75 mmol) and the aryne precursor 2 (0.75 mmol). When TLC control showed the completion of the reaction (typically after 12 h), the reaction stopped and the crude reaction mixture was purified by column chromatography on silica gel to afford the corresponding indolin 2-one derivatives 8 in good yields.

According to the analysis of related databases, 60434-13-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH; THANKAPPAN, Biju Akkattu; BHUNIA, Anup; ROY, Tony; WO2014/184808; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 7699-18-5, 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 7699-18-5 as follows.

General procedure: To the phenstatin-3-aldehyde/isocombretastatin-3-aldehyde(16a-b) (0.303 mmol/0.304 mmol) prepared in the above stepwas added corresponding substituted oxindoles (17a-h)(0.303 mmol) and catalytic amount of piperidine (1.0 ml) in ethanol.Heated the reaction mixture to reflux for 4 h at 85 C. The solidcompounds obtained in the reaction vessel were filtered and washed with ethanol for 4-5 times. After complete air drying thefinal compounds phenstatin/isocombretastatin-oxindole analogs(5a-h and 6a-h) were obtained as pure solids (yield 71-90%).

According to the analysis of related databases, 7699-18-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kumar, G. Bharath; Nayak, V. Lakshma; Sayeed, Ibrahim Bin; Reddy, Vangala Santhosh; Shaik, Anver Basha; Mahesh, Rasala; Baig, Mirza Feroz; Shareef, Mohd Adil; Ravikumar; Kamal, Ahmed; Bioorganic and Medicinal Chemistry; vol. 24; 8; (2016); p. 1729 – 1740;,
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. 356068-93-4, name is (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 356068-93-4

To a stirred solution of compound 1 (0.5 g, 1.67 mmol) in DMF (35 mL) at room temperature was added etaOBt (1.02 g, 7.52 mmol), triethylamine(2.12 mL, 15.03 mmol), ECDIetaC1(1.44 g, 1.52 mmol) and methyl 4-aminobutanate hydrochloride(0.77 g, 5.0 mmol) successively. The mixture was stirred for 24 h at room temperature and then was diluted with water (20 mL), brine (20 mL) and saturated bicarbonate solution (20 mL) and the peta of solution was adjusted to 11-12 with 10 mol/L NaOH. The mixture was filtrated, the solid was collected, washed with water and dried to obtain crude yellow solid product 110-3 (0.32 g, 48.3%). LCMS: m/z 400(M+l), 1U NMR(DMSO-J6) deltal.77 (m, 2eta), 2.39 (m, 4H), 2.42 (s, 3H), 2.49 (s, 3H), 3.23 ( t, 2H), 6.85 (m, 2H), 7.60 (t, IH), 7.67 (s, IH), 7.71 (m, IH), 10.89 (s, IH), 13.68 (s, IH).

According to the analysis of related databases, 356068-93-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CURIS, INC.; WO2008/33747; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 320734-35-8, A common heterocyclic compound, 320734-35-8, name is 7-Bromooxindole, molecular formula is C8H6BrNO, 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 cooled (-78C) solution of 7-bromooxindole (4.7g; 22.16 mmol) and N,N,N?, N?tetramethylethylenediamine (10.97 mL; 73.17 mmol) in dry THF (230 mL) was slowly added n-butyllithium solution (19.S mL; 48.76 mmol; 2.S M in hexane). The solution was stirred for 30 minutes at the same temperature and then, iodomethane (1.65 mL; 26.6 mmol) was added slowly. The reaction mixture was stirred at -20C for 1.5h, then,quenched with a saturated aqueous solution of NH4C1 and extracted with EtOAc.The organic layer was sried over MgSO4, filtered and concentrated in vacuo. The resultingcrude material was purified by silica gel chromatography (mobile phase: heptane/EtOAc)to afford, after solvent evaporation, 1.3 g (22%) of intermediate 217.

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; JANSSEN PHARMACEUTICA NV; STANSFIELD, Ian; QUEROLLE, Olivier, Alexis, Georges; LIGNY, Yannick, Aime, Eddy; GROSS, Gerhard, Max; JACOBY, Edgar; MEERPOEL, Lieven; GREEN, Simon, Richard; HYND, George; KULAGOWSKI, Janusz, Jozef; MACLEOD, Calum; MANN, Samuel, Edward; (419 pag.)WO2018/2219; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-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 2058-72-2, Recommanded Product: 5-Bromo-1-methylindoline-2,3-dione

General procedure: The mixture of corresponding 2-amino-4-arylimidazoles 1 (1.0 mmol), isatin 18 (1.0 mmol) and ethyl 2-cyanoacetate 15 (1.0 mmol) in 2 mL of 2-propanol was refluxedduring 50-60 min. After cooling, the solid products 20were filtered off and crystallized from iPrOH.

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, 5-Bromo-1-methylindoline-2,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Lipson, Victoria V.; Pavlovska, Tetiana L.; Svetlichnaya, Nataliya V.; Poryvai, Anna A.; Gorobets, Nikolay Yu.; Van Der Eycken, Erik V.; Konovalova, Irina S.; Shiskina, Svetlana V.; Borisov, Alexander V.; Musatov, Vladimir I.; Mazepa, Alexander V.; Beilstein Journal of Organic Chemistry; vol. 15; (2019); p. 1032 – 1045;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

13220-46-7, name is 4-Methylindolin-2-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. SDS of cas: 13220-46-7

4-(2-Carboxyethyl)-2-formyl-3-methylpyrrole (90 mg), 74 mg 4-methyl-2-oxindole, and 75 muL piperidine in 2 mL of ethanol were heated at 95 C. for 5 hours. The reaction mixture was cooled and concentrated. The residue was suspended in 6 N aqueous hydrochloric acid. The precipitate was filtered, washed with water to pH 6 and dried in a vacuum oven to give 80 mg (52%) of the title compound as a brown solid.1HNMR (360 MHz, DMSO-d6): delta 13.33 (s, br, 1H, NH-1′), 10.84 (s, br, 1H, NH-1), 7.54 (s, 1H, H-vinyl), 7.12 (d, J=2.0 Hz, 1H, H-2′), 7.01 (t, J=7.75 Hz, 1H, H-6), 6.79 (d, J=7.75 Hz, H-5), 6.74 (d, J=7.75 Hz, 1H , H-7), 2.64 (t, J=7.65 Hz, 2H, CH2CH2COOH), 2.57 (s, 3H, CH3), 2.42 (t, J=7.65 Hz, 2H, CH2CH2COOH), 2.19 (s, 3H, CH3); MS m/z (relative intensity, %) 311 ([M+1]+, 100).

The synthetic route of 13220-46-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sugen, Inc.; US6878733; (2005); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 56341-37-8, 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. 56341-37-8 name is 6-Chlorooxindole, 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.

[Step 1] (3E/Z)-6-chloro-3-[(2-chloro-3-fluoropyridin-4-yl)methylene]-1,3-dihydro-2H-indol-2-one [0083] N,N-Diisopropylethylamine (0.46 ml, 2.63 mmol) was added to a methanol (130 ml) solution of 6-chloro-1,3-dihydro-2H-indol-2-one (2.20 g, 13.11 mmol) and 2-chloro-3-fluoroisonicotinaldehyde (2.20 g, 13.8 mmol) and the resulting mixture was heated to reflux for 16 hours. After cooling, the precipitate was collected by filtration, washed with cold methanol and dried to give 3.37 g (83%) of the title compound as a solid. MS (APCI) m/z: 309 (M+H)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Chlorooxindole, and friends who are interested can also refer to it.

Reference:
Patent; Daiichi Sankyo Company, Limited; YOSHIDA, Shoko; SUGIMOTO, Yuuichi; EP2894156; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem