Indolines-derivatives

Electric Literature of 18711-13-2,Some common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, molecular formula is C8H3Cl2NO2, 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: The NiO-SiO2 catalyst (6.5 mol%) was added to a mixture of isatin (1 mmol), malononitrile (1 mmol), and 3-methyl-1-phenyl-1H-pyrazol-5-amine (1 mmol) in EtOH, and the reaction flask was placed in an oil bath and refluxed for the appropriate time. The progress of reaction was monitored by TLC. After the completion of the reaction, the heterogeneous catalyst was recovered from the reaction mixture by filtration. The filtrate was evaporated to afford the crude solid product which was later purified by column chromatography. The solid catalyst was washed with hot EtOH and then dried in oven to reuse.

The synthetic route of 18711-13-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yagnam, Swetha; Akondi, Adinarayana Murthy; Trivedi, Rajiv; Rathod, Balaji; Prakasham, Reddy Shetty; Sridhar; Synthetic Communications; vol. 48; 3; (2018); p. 255 – 266;,
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. 32692-19-6, name is 5-Nitroindoline, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 32692-19-6

5-Nitro-1-(2-(pyrrolidin-1-yl)ethyl)indoline (3) A solution of compound 2 (500 mg, 3.05 mmol) in DMF (10 mL) was treated with NaH (390 mg, 9.75 mmol, 60% wt in mineral oil) at 0 C. resulting in a bright orange suspension. The mixture stirred for 10 minutes, then 2-chloroethyl-pyrrolidine hydrochloride (566 mg, 3.33 mmol) was added and the reaction turned into a bright red suspension. The reaction was heated to 90 C. for 1 hour. After 1 hour, the reaction was allowed to cool to room temperature. Then it was diluted with water (20 mL), transferred to a separatory funnel and extracted with ethyl acetate (2*15 mL). The combined the organic layers were washed with brine (3*5 mL), dried (Na2SO4), filtered and concentrated. The residue was subjected to flash chromatography on silica gel using: 2.5% 2M NH3 in methanol: 97.5% CH2Cl2 to give a brown solid (400 mg, 50%). 1H-NMR (DMSO-d6) delta 7.96 (dd, J=2.4, 9.0 Hz, 1H), 7.80 (d, J=2.1 Hz, 1H), 6.47 (d, J=9.0 Hz, 1H), 3.73 (t, J=9.0 Hz, 2H), 3.41 (t, J=6.9 Hz, 2H), 3.04 (t, J=8.1 Hz, 2H), 2.62 (t, J=6.9 Hz, 2H), 2.58-2.48 (m, 4H), 1.70-1.64 (m, 4H).

According to the analysis of related databases, 32692-19-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MADDAFORD, Shawn; RAMNAUTH, Jailall; RAKHIT, Suman; PATMAN, Joanne; ANNEDI, Subhash C.; ANDREWS, John; DOVE, Peter; SILVERMAN, Sarah; Renton, Paul; US2008/234237; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 89-40-7, The chemical industry reduces the impact on the environment during synthesis 89-40-7, name is 5-Nitroisoindoline-1,3-dione, I believe this compound will play a more active role in future production and life.

General procedure: The substrate (0.5 mmol), NiPd/MIL-101 catalyst (0.023g, Pd 0.2 mol%), and ethyl acetate (4 mL) were added to a Schlenk tube, and the mixture was vigorously stirred with an affixed hydrogenation balloon at room temperature. Following the reaction, the solid catalyst was removed from the solution by filtration and washed with ethyl acetate. The product yields were determined by gas chromatography-mass spectrometry (GC/MS, Shimadzu GCMS- QP5050A) with a 0.25 mm ¡Á 30 mDB-WAX capillary column. Parameters were as follows: initialoven temperature, 100 C, 1 min; ramp, 20 C/min; final temperature, 280 C; final time, 5 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, 5-Nitroisoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Jian, Siping; Li, Yingwei; Cuihua Xuebao/Chinese Journal of Catalysis; vol. 37; 1; (2016); p. 91 – 97;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 14192-26-8, 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. 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

The intermediate from Step D was esterified by heating in acidic methanol overnight. The resulting solution was concentrated under vacuum and the residue was dissolved in hot ethanol (75 mL). Methanol (20 mL) was added to redissolve some material that precipitated as the solution cooled. Sodium nitrite (1.50 g) was added, followed by concentrated hydrochloric acid (5 mL). The reaction was stirred for 2 h, and a further concentrated hydrochloric acid (2 mL) was added. The reaction was stirred overnight. Volatiles were removed under reduced pressure, water added, and the resulting yellow orange product was isolated by filtration and dried under vacuum to give the intermediate (2.1 g) as a yellow orange solid. [MH]+=221.

The chemical industry reduces the impact on the environment during synthesis Methyl 2-oxoindoline-6-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Alantos Pharmaceuticals, Inc.,; US2006/173183; (2006); 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 7699-18-5 as follows. COA of Formula: C9H9NO2

General procedure: To the 3-subtitutedphenyl-1H-pyrazole-5-carbaldehydes 11(a-d) prepared in the above step was added corresponding substituted oxindoles and catalytic amount of piperdine (1.0ml) in ethanol. Heated the reaction mixture to reflux for 4h at 85C. The solid compounds obtained in the reaction vessel were filtered and washed with ethanol for 4-5 times. After complete air drying the final compounds (Z)-3-((3-phenyl-1H-pyrazol-5-yl)methylene)indolin-2-one analogs 12(a-u) were obtained as pure solids (yield 75-80%).

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; Kamal, Ahmed; Shaik, Anver Basha; Jain, Nishant; Kishor, Chandan; Nagabhushana, Ananthamurthy; Supriya, Bhukya; Bharath Kumar; Chourasiya, Sumit S.; Suresh, Yerramsetty; Mishra, Rakesh K.; Addlagatta, Anthony; European Journal of Medicinal Chemistry; vol. 92; (2015); p. 501 – 513;,
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. 65826-95-1, name is 5-Methylindoline, A new synthetic method of this compound is introduced below., Product Details of 65826-95-1

EXAMPLE 54 2-(5-Methylindolin-1-yl)benzonitrile A slurry of 5-methylindoline (31 g, 0.23 mole), sodium hydride (11.3 g, 60% in oil) and dimethylsulfoxide (120 ml) was stirred at room temperature for 1 hour. A solution of o-fluorobenzonitrile (31 gm, 0.25 mole) in dimethylsulfoxide (25 ml) was added dropwise at a temperature below 20 C. Upon completion of the addition, the mixture was stirred for 2 hours at room temperture. The reaction mixture was partitioned between methylene chloride (700 ml) and ice-water (700 ml). The dichloromethane solutions were separated. The aqueous phase was extracted with dichloromethane (2 times, 600 ml). The combined dichloromethane solutions were washed with 2N hydrochloric acid (2 times, 500 ml), water (500 ml), brine (2 times, 400 ml), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was dissolved in ethanol (300 ml) and heptane (100 ml), and chilled in a freezer. The precipitate was collected. The mother liquor was concentrated and purified by flash chromatography on a silica gel column (400 g, 230-400 mesh) eluted with hexane:dichloromethane (3:1, 3 l); hexane:dichloromethane (1:1, 2 l) and dichloromethane (2 l). The fractions containing product were pooled and concentrated to yield 33 g (73% overall yield). The analytical sample was prepared by high-pressure liquid chromatography (Water Associates Prep 500, 10 g, 2 chamber, elution with hexane:dichloromethane, 9:1, 12 l) followed by crystallization from ethanol, mp 59-60 C. ANALYSIS: Calculated for C16 H14 N2: 82.02%C 6.02%H 11.96%N. Found: 82.47%C 6.08%H 12.10%N.

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; Hoechst-Roussel Pharmaceuticals Inc.; US4663453; (1987); A;,
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 675109-26-9 as follows. SDS of cas: 675109-26-9

6-Bromoisoindolin-l-one (4 g, 18.9 mmol) was suspended in 70 ml of THF and cooled to 0-5C. Sodium hydride (60% in mineral oil) (1.5 g, 37.7 mmol, 2 equiv.) was added in portions at 0-5C and after 5 minutes (2RS)-2-bromo-2-phenyl-acetic acid (4.34 g, 20.2 mmol, 1.07 equiv.) were added and the mixture was stirred at 0-5 C for 2 hours. The reaction mixture was extracted with 1M HC1 solution and twice with ethyl acetate. The organic layers were dried over sodium sulfate and evaporated to dryness to obtain the desired (2RS)-2-(6-bromo-l-oxo-isoindolin-2-yl)-2- phenyl-acetic acid (5.78 g, 89 % yield) as a white solid, MS: m/e = 345.9/347.9 (M+H+).

According to the analysis of related databases, 675109-26-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; C4 THERAPEUTICS, INC.; DUPLESSIS, Martin; JAESCHKE, Georg; KUHN, Bernd; LAZARSKI, Kiel; LIANG, Yanke; NAGEL, Yvonne Alice; RICCI, Antonio; RUEHER, Daniel; STEINER, Sandra; (46 pag.)WO2019/149922; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 959235-95-1, 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. 959235-95-1 name is 6-(Trifluoromethoxy)indoline, 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.

To a solution of 2-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4-chlorophenyl)-2-((3-methoxy-5-(methylsulfonyl)phenyl)amino)acetic acid 5d (1 .07 g, 1 .97 mmol) inDMF (10 mL) were added HATU (1 .12 g, 2.95 mmol), diisopropylethylamine (976 pL, 5.91 mmol) and 6-(trifluoromethoxy)indoline [CAS 959235-95-1] (400 mg, 1 .97 mmol). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water. The precipitate was filtered off, washed with waterand taken up with EtOAc. The organic layer was washed with a 10% solution ofK2003, water, dried over MgSO4, filtered and the solvent was concentrated under reduced pressure to give 2-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4-chlorophenyl)-2-((3-methoxy-5-(methylsulfonyl)phenyl)amino)-1 -(6-(trifluoromethoxy)indolin-1-yl)ethanone 6a (1.36 g). The crude compound wasused without purification in the next reaction step.

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

Synthetic Route of 114041-16-6,Some common heterocyclic compound, 114041-16-6, name is 5,6-Dimethoxyisoindoline, molecular formula is C10H13NO2, 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.

Step e: simultaneous preparation of 1-(5,6-dimethoxyisoindolin-2-yl)-6-[4-(3-trifluoromethyl-phenyl)piperazin-1-yl]hexan-1-one, 1-isoindolin-2-yl-6-[4-(2-cyanophenyl)piperazin-1-yl]hexan-1-one and 1-isoindolin-2-yl-6-[4-(2-methyl-phenyl)piperazin-1-yl]hexan-1-one A mixture of 0.3 mmol of dicyclohexylcarbodiimide and 0.3 mmol of 1-hydroxybenzotriazole is added to a solution of acid (0.3 mmol) in 2 mL of anhydrous N,N-dimethylformamide. The mixture is left whilst stirring for four hours at 70 C. It is then cooled at ambient temperature, filtered in order to eliminate the dicyclohexylurea. Amine (0.2 mmol) is then added, then it is left for twenty hours at ambient temperature. The N,N-dimethylformamide is evaporated out in a vacuum and the crude is taken up by 2 mL of dichloromethane. It is then washed twice with 1 mL of a normal aqueous solution of soda, then with 1 mL of water. The organic phase is dried then concentrated in a vacuum. Starting from 6-[4-(3-trifluoromethyl-phenyl)piperazin-1-yl]hexanoic acid and 5,6-dimethoxyisoindoline, 1-(5,6-dimethoxyisoindolin-2-yl)-6-[4-(3-trifluoromethylphenyl)piperazin-1-yl]hexan-1-one is obtained in this way. Rf: 0.76 dichloromethane/methanol 85/15

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5,6-Dimethoxyisoindoline, its application will become more common.

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. 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Formula: C10H9Cl2NO

Preparation of 5-(2-(4-(l ,2-benzisothiazol-3-yl)-1 -piperazinyl)ethvD-6-chloro-l ,3-dihydro-2H-indol-2-one(Ziprasidone)In a 50 ml 3 necked round bottom flask there were placed 1 gram (4.56 mmol) of 3-piperazinylbenzo[d]isothiazole; 1.25 grams (5.43 mmol) of 6-chloro-5-(2-chloroethyl)indolin-2-one; 50 mg of potassium iodide; 0.82 gram (5.94 mmol) ofpotassium carbonate and 3 ml of sulfolane. The contents of the flask were heated to 95C to 100 C. The reaction was monitored by HPLC. After completion of the reaction, 50ml of DM water was added to the reaction mixture and stirred. The product was filtered off and washed with water and dried to obtain 1.41 grams (75%) of 5-(2-(4-(l,2-benzisothiazol-3-yl)-l-piperazinyl)ethyl)-6-chloro-l,3-dihydro-2H-indol-2-one. The crude product was purified by IPA and/ or THF. The product matched the spectra of a standard NMR and showed the correct retention time by HPLC with 98.0% assay. The melting point of the compound was found to be 218C -220 C, and was found to conform with the melting point of 218 -220 C as disclosed in US. 5,206,366. Example 3Preparation of 5-(2-(4-(‘l,2-benzisothiazol-3-vD-l-piperazinvDethvl)-6-chloro-l,3-dihydro-2H-indol-2-one(Ziprasidone)In glass-lined reactor placed 21.1 Kg (96.34 mole) of 3-piperazinylbenzo [d]isothiazole; 31 kg (134.7 moles) of 6-chloro-5-(2-chloroethyl)indolin-2-one; 1.1 kg ofpotassium iodide; 20.0 kg (111.92 mole) of potassium carbonate and 63.2 lit ofsulfolane. The contents of the flask were initially heated to 75C to 80 C for 2 hrs.Then temperature was raised to 95C to 100 C and stirred till completion of thereaction. After completion of the reaction 210 lit of DM water was added to the reaction mixture and stirred. The product was filtered off and washed with water and dried to obtain 29.75 kg of 5-(2-(4-(l,2-benzisothiazol-3-yl)-l-piperazinyl)ethyl)-6-chloro-l,3-dihydro-2H-indol-2-one (Ziprasidone).

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