Author: tianli

104618-32-8, Name is 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, 104618-32-8, 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.

EXAMPLE 3 3-Amino-6-methoxy-1,2,3,4-tetrahydrocarbazole hydrochloride Reaction of 4-methoxyphenyl hydrazine hydrochloride (0.87 g, 5.0 mmol) with 4-phthalimido-cyclohexanone (1.22 g, 5.0 mmol) in ethanol (20 ml) heated under reflux for 2 hr, followed by cooling and removal of the precipitated solid by filtration gave 3-phthalimido-6-methoxy-1,2,3,4-tetrahydrocarbazole (1.62 g).

Statistics shows that 2-(4-Oxocyclohexyl)isoindoline-1,3-dione is playing an increasingly important role. we look forward to future research findings about 104618-32-8.

Reference:
Patent; SmithKline Beecham P.L.C.; US5464864; (1995); A;,
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. 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, This compound has unique chemical properties. The synthetic route is as follows., 118289-55-7

2. Preparation of ZPR in glycerol In a three necked flask was charged BITP HC1 (25g, 0. 098 mol), glycerol (62 ml), Na2C03 (13g) and the mixture was stirred for 10 minutes. CEI (5.9g) was added and the reaction mixture was heated for 3h at 115-120C. After 3h, the reaction was almost complete; after cooling to room temperature the solid was filtrated and was triturated in water and dried. The dried solid weights 42 g and the purity was 89.03%.

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; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2005/40160; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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-Bromo-2-Oxindole 2-Oxindole (1.3 g) in 20 mL acetonitrile was cooled to -10 C. and 2.0 g N-bromosuccinimide was slowly added with stirring. The reaction was stirred for 1 hour at -10 C. and 2 hours at 0 C. The precipitate was collected, washed with water and dried to give 1.9 g (90% yield) of the title compound.

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

Reference:
Patent; Sugen. Inc.; US2003/100555; (2003); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

A common compound: 4403-36-5, name is 2-(1,3-Dioxoisoindolin-2-yl)ethanesulfonylchloride, belongs to indolines-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 4403-36-5

To a solution of 2-{3-exo-[(R)-1-((S)-2-methyl-propane-2-sulfinylamino)-2-(2,4,5-trifluoro- phenyO-ethylJ-beta-aza-bicyclop^.ijoctane-beta-sulfonylJ-ethylamine (100 mg, 0.202 mmol) in dichloromethane / 2N NaOH (2 mL, 1/1) are 2-phtalimidoethanesulfonyl chloride (167 mg, 0.605 mmol). The resulting solution is stirred at 500C during 2h before extraction and evaporation of organic phase to yield the crude compound. It is purified by preparative HPLC (Column Waters C18 ODB 5mum 19×50, Gradient: 0-2.5 min 5% ACN, 2.5-12.5 min 5-100% ACN, 12.5-15 min 100% ACN) to yield title compound. MS: 734 [M+H]+HPLC (Zorbax SB C18, 2min method (0-0.8min 10-95%ACN, 0.8-1.5min 95%ACN, 1.5- 1.6min 95-10%ACN, 1.6-2min 10%ACN): 1.43 min.

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, 4403-36-5, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2007/115821; (2007); A2;,
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 118-29-6 as follows. 118-29-6

200 mL of sulfuric acid were cooled to 0 0C. 48 g of 2,3,3 – trimethylindolenine were added to the sulfuric acid followed by the addition of 54 g of N-hydroxymethyl-phthalimide. The reaction mixture was stirred at room temperature for 7 days. The reaction mixture then was added to 500 g of crushed ice in a 2000-mL conical flask immersed in ice-salt bath. A solution of about 225 g of sodium hydroxide in 500 mL of water was cooled to 10 0C and then added dropwise to the magnetically stirred mixture in the conical flask. A white precipitate starts to form after addition of about half of the solution of sodium hydroxide. Addition of the sodium hydroxide is continued until the pH of the reaction mixture is strongly basic (pH > 12). The white solid is then filtered, washed with water (3×100 mL) and air- dried on a Buchner funnel for about 1 hour. The solid is then transferred to a 1000- mL one -neck round bottom flask, 300 mL of acetone is added and the mixture is stirred under reflux for 30 min. The flask is then cooled to 10 0C and the white product is filtered with suction on a Buchner funnel, washed with acetone (1 x50 mL), and air dried.The yield of the pure product is 70-75% (67-7O g). NMR: (DMSO-d6, 300 MHz) delta 1.33 (s, 6H, 2xCH3), 2.31 (s, 3H, CH3), 4.91 (s, 2H, CH2), 7.32 (dd, 3JH-H =8.7 Hz, 5Jn-H – 1.2 Hz, IH), 7.48 (dd, 5JH-H = 8.7 Hz, IH), 7.51 (dd, 5JH-H = 1.2 Hz, IH, 7.9-8.1 (m, 4H).; 6.1 2-(2, 3, 3-Trimethyl-3H-indol-5-ylmethyl)-isoindole-l, 3-dione, 1Sulfuric acid (420.0 mL, 7.879 mol; Sigma-Aldrich) was placed to the 1 L one -neck, round-bottom flask equipped with magnetic stirrer. The flask was cooled in ice-water bath and 2,3,3-trimethyl-3H-Indole, (100.0 g, 0.6280 mol; Sigma-Aldrich) was added to the sulfuric acid by drops during 45 min with stirring. The reaction mixture becomes a very viscous upon addition of 2,3,3-trimethyl-3H-indole, so stirring plate with adequate power and large magnetic stir bar is required. When addition of 2,3,3-trimethyl-3H-Indole was completed the ice bath was removed and 2- (hydroxymethyl)-lH-Isoindole-l,3(2H)-dione, (112 g, 0.632 mol; Aldrich) was added to the reaction mixture at once. The flask was closed with a glass stopper and the stirring was continued for 168 hours at room temperature. In about 12 hours all solid, 2-(hydroxymethyl)-lH-Isoindole-l,3(2H)-dione dissolved and clear brown solution formed.After 168 hours the content of the flask was poured into 4-L conical flask containing 1 kg of ice. The 4-L flask was immersed in ice-salt bath, equipped with mechanical stirrer. A cooled to 10 0C solution of 550g of NaOH in 1.5 L of water was slowly added to the reaction mixture at such rate that temperature inside of flask didn’t increase higher than 20 0C. The addition takes about 1 hour. The white precipitate formed was filtered on Buchner funnel with suction and dried on air for 12 hours.The crude 2-(2,3,3-Trimethyl-3H-indol-5-ylmethyl)-isoindole-l,3-dione was placed in conical 2 L flask, 1 L of acetone was added and the mixture was magnetically stirred with heating until acetone start to boil. The heating was reduced to maintain a very gentle boiling and the content of the flask was stirred for additional 10 min. Flask was cooled using ice-water bath and the separated crystals were filtered, washed with acetone and dried. The yield of the first crop with m.p. = 186-187 0C was 82 g. The mother liquor was reduced in volume to about 300 mL and cooled at -10 0C overnight. The separated crystals were filtered, washed with acetone and dried. The yield of the second crop with m.p. = 184-185 0C was 45 g. The total yield was 126 g (63% of theoretical).Analytical Results for 1:M.p. = 186-187 0C1H NMR (CDCl3, 300 MHz) delta 1.28 (s, 6H), 2.25 (s, 3H), 4.87 (s, 2H), 7.38- 7.45 (m, 3H), 7.68-7.71 (m, 2H), 7.83-7.86 (m, 2H). 13C NMR (CDCl3, 75 MHz) delta 15.4, 23.0, 41.7, 53.7, 119.8, 122.0, 123.3, 128.4,132.2, 133.3, 133.9, 146.1, 153.5, 168.0, 188.5.

According to the analysis of related databases, 118-29-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL; WO2008/157762; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

20876-36-2,Some common heterocyclic compound, 20876-36-2, name is 5-Aminoindolin-2-one, molecular formula is C8H8N2O, 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.

A THF (20 mL) solution of 5-aminoindolin-2-one (200 mg, 1.3 mmol) and di-t-butyl dicarbonate (300 mg, 1.4 mmol) at rt under N2, was treated with Et3N (0.37 mL, 2.7 mmol). The stirring was continued at rt overnight; the reaction mixture was concentrated under reduced pressure, taken into DCM and washed (H2O 2x, brine). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Trituration with hexanes provided the title compound as a white solid (260 mg, 77 percent). 1H NMR (400 MHz, CDCl3) delta ppm 7.43 (br. s., 2 H), 7.07 (dd, J=8.84, 1.26 Hz, 1 H), 6.77 (d, J=8.59 Hz, 1 H), 6.39 (br. s., 1 H), 3.52 (s, 2 H), 1.52 (s, 9 H); MS ESI 249.0 (80) [M + H]+, calcd for [C13H16N2O3 + H]+ 249.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 20876-36-2, its application will become more common.

Reference:
Patent; UNIVERSITY HEALTH NETWORK; WO2009/79767; (2009); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. 2058-72-2

General procedure: Triethanolamine (20 mol %) wasadded to a solution of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide(1) (0.198 g, 0.001 mol), malononitrile (2) (0.066 g,0.001 mol), and appropriate isatin 3a-n (0.001 mol) in EtOH (5-10 ml). The mixture was refluxed for 1 h. The obtained precipitates of compounds 4a-n were filtered off,washed with EtOH, dried in air, and recrystallized from EtOH-DMF, 1:1.

The synthetic route of 2058-72-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Grygoriv, Galina V.; Lega, Dmitry A.; Zaprutko, Lucjusz; Gzella, Andrzej K.; Wieczorek-Dziurla, Ewa; Chernykh, Valentine P.; Shemchuk, Leonid A.; Chemistry of Heterocyclic Compounds; vol. 55; 3; (2019); p. 254 – 260;,
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. 99365-40-9, name is 6-Bromoindolin-2-one, A new synthetic method of this compound is introduced below., 99365-40-9

Sodium hydride (4.53 g, 94.3 mmol, Eq: 4) and dry tetrahydrofuran (20 ml) were mixed under argon. A suspension of 6-bromoindolin-2-one (5 g, 23.6 mmol, Eq: 1.00) in dry tetrahydrofuran (50 ml) was added in portions. The mixture was stirred at room temperature for 20 min. Then iodomethane (13.4 g, 5.87 ml, 94.3 mmol, Eq: 4) was added dropwise at 23-26 C. The light brown suspension was stirred at room temperature overnight. The reaction mixture was carefully quenched with 10 ml of saturated ammonium chloride. The mixture was diluted with 200 ml of ethyl acetate, 100 ml of water and 50 ml of saturated sodium bicarbonate. The mixture was extracted with 100 ml of ethyl acetate (2x) and the organic layers were washed with 50 ml of saturated sodium bicarbonate. The combined organic layers were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the desired product a white solid (4.16g, 69 %). MS (m/z) = 254.4/256.4 [M + H]+.

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; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; GAUFRETEAU, Delphine; KOLCZEWSKI, Sabine; PLANCHER, Jean-Marc; STOLL, Theodor; (99 pag.)WO2017/76842; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-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. 2058-72-2

General procedure: A mixture of isatin (1) (2.0 mmol), L-proline (2) (2.0 mmol) and acrylonitrile/methyl acrylate (3/5) (2.0 mmol) in 10 mL of water was heated in an oil bath at 80 C for 3 to 6 hours. Initially reaction mixture appeared to be homogeneous but with the progress of reaction the solid precipitated out. TLC indicated the consumption of L-proline and acrylonitrile while isatin was remaining in small portion. The reaction mixture was extracted many times with ethylacetate (EA). The combine organic layer was dried over anhydrous Na2SO4 and evaporated on rotary evaporator to provide yellow colour solid. The solid was purified by silica gel column chromatography using EA:hexane (4:6) as an eluent to provide desired product 4 and 6 as white solid. The yield mentioned in the analytical data has been calculated after recovering the unreacted isatin (amount mentioned in characterization data).

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 2058-72-2.

Reference:
Article; Tiwari, Keshri Nath; Pandurang, Taur Prakash; Pant, Suyash; Kumar, Rahul; Tetrahedron Letters; vol. 57; 21; (2016); p. 2286 – 2289;,
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 59-48-3 as follows. 59-48-3

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-vitro-2-oxindole.

According to the analysis of related databases, 59-48-3, the application of this compound in the production field has become more and more popular.

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