Author: Jessica.F

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. 6872-06-6, name is 2-Methylindoline, A new synthetic method of this compound is introduced below., Formula: C9H11N

Example 4Synthesis of 5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)sulfonyl)-1-((4-fluorophenyl)sulfonyl)-2-methylindolineReagents MW Mole Reagent/raw material (g/mole) Quantity moles ratio 2-methylindoline 161.20 177 mg 1.33 mmol 1 eq. 4-fluorobenzene-1- 194.61 235 mg 1.33 mmol 1.0 eq. sulfonyl chloride 1-((4-fluorophenyl)sulfo- 291.34 267 mg 0.88 mmol 1.0 eq. nyl)-2-methylindoline 2,3-dihydro- 234.66 206 mg 0.88 mmol 1.0 eq. benzo[b][1,4]dioxine- 6-sulfonyl chloride Aluminium chloride 133.3 147 mg 1.1 mmol 1.25 eq. Step I: 2-methylindoline was dissolved in 5 mL dry pyridine, and 4-methoxybenzene-1-sulfonyl chloride was dropped in 2 portions under N2. The reaction was stirred for 2 hours at room temperature and an intense red color developed. When the reaction was complete as determined by HPLC using the protocol described above, as well as by TLC (8/2 PE/EtOAC), the crude reaction mixture was poured into 100 mL cold 0.5M HCl, and extracted twice with 50 mL CH2Cl2. The organic phase was evaporated, and the evaporation residue was purified by passing through a silica plug (100 g silica gel in large sinter glass). The product eluted in 7/3 PE/EtOAC, while all of the pink polar byproduct was retained on silica. The organic phase was dried on Na2SO4, and then evaporated and used for the next step without further purification (Product 100% pure, 378 mg, yield 99%).

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; Becker, Oren M.; Shitrit, Alina; Schutz, Nili; Ben-Zeev, Efrat; Yacovan, Avihai; Ozeri, Rachel; Kehat, Tzofit; Mirilashvili, Sima; Aizikovich, Alex; Sherman, Daniel; Behar, Vered; Kashtan, Osnat; US2012/108631; (2012); 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 496-12-8 as follows. Application In Synthesis of Isoindoline

To a solution of 3,4-(methylenedioxy)aniline (150 mg, 1.09 mmol) in dry DCM (4 mL) was added dropwise phenyl chloroformate (0.138 ml, 1.09 mmol) and triethylamine (0.153 ml, 1.09 mmol). After the reaction mixture was stirred at r.t for 8 hr., isoindoline (0.123 ml, 1.09 mmol) and triethylamine (0.153 ml, 1.09 mmo) were added, and the reaction mixture was stirred overnight. The solvent was then removed under reduced pressure, and the residue was purified by chromatographed on silica gel (EtOAC/Hexane: 1:3) to give the title compound (185 mg, 60%) as a white solid: m.p:165-166 C. 1H NMR (CDCl3, 500 MHz): 4.82 (s, 4H); 5.93 (s, 2H); 6.20 (s, 1H); 6.73 (s, 2H); 7.17 (s, 1H); 7.30 (m, 4H). MS (MH+, 283).

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:
Patent; Tachdjian, Catherine; Patron, Andrew P.; Adamski-Werner, Sara L.; Bakir, Farid; Chen, Qing; Darmohusodo, Vincent; Hobson, Stephen Terrence; Li, Xiaodong; Qi, Ming; Rogers, Daniel Harry; Rinnova, Marketa; Servant, Guy; Tang, Xiao-Qing; Zoller, Mark; Wallace, David; Xing, Amy; Gubernator, Klaus; US2005/84506; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 20870-90-0, 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. 20870-90-0 name is 5-Bromo-1-methyl-2-oxoindoline, 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 5-bromo-1-methyl-1 ,3-diotahydro-iotandol-2-one (CASNo. 20870-90-0, 80 mg, 0 35 mmol) was added 5-methyl-3-pyndmyl boronic acid (CASNo. 173999-18-3 55 mg, 0 39 mmol), in 1 ,2-diotamethoxyethane (2 7 mL) and 2 M aqueous sodium carbonate (0 45 mL, 0 9 mmol) The reaction mixture was degassed and placed under an argon atmosphere, at which time resin bound tetrakiotas(triotaphenylphosphiotane)palladiotaum(0)( specifically polystyrene triphenytphosphine palladium (0) [PS-PPh3-Pd(O) (Biotage), 0 09 mmol/g loading (195 mg, 0 018 mmol)] was added The reaction vessel was sealed and was heated by microwave irradiation at 100 C for 1.5 hours The reaction mixture was cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane 0 to 6%) to afford 1-methyl-5-(5-methyl-pyridiotan-3-yl)-1 3- dihydro-iotandol-2-one, HRMS (ESI) m/z 239 1 181 (M+H)Phi, 1H NMR (400 MHz, CDCI3) delta ppm 2,42 (s, 3 H), 3 27 (s, 3 H), 3 61 (s, 2 H), 6 93 (d, J=8 1 Hz, 1 H) 7 45 – 7.58 (m, 2 H), 7 67 (S1 1 H), 8 42 (s, 1 H), 8.63 (s, 1 H)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromo-1-methyl-2-oxoindoline, and friends who are interested can also refer to it.

Reference:
Patent; NOVARTIS AG; ADAMS, Christopher Michael; CHAMOIN, Sylvie; HU, Qi-Ying; ZHANG, Chun; WO2010/130794; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

32692-19-6, name is 5-Nitroindoline, 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. Product Details of 32692-19-6

To a stirred solution of chlorosulfonyl isocyanate ( 3.67 g , 26 mmol) in DCM ( 5 ml ), t- butanol (2.07g , 28 mmol) was added dropwise at 0 C under nitrogen atmosphere and stirred for 15 min. This mixture was added to a solution of 5-Nitroindoline (3.7 g, 22 mmol) and TEA ( 6.66 g , 66 mmol) in DCM ( 50 ml ) at 0 C under nitrogen atmosphere and stirred at rt for 8 hr . Solvent was evaporated , water (30 ml ) was added to the residue & the yellow solid was filtered and dried (7.53 g , 90.24%). MS = m/z 343 [M-I].

The synthetic route of 32692-19-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LUPIN LIMITED; WO2009/109999; (2009); 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. 39755-95-8, name is 5-Methoxyisatin, A new synthetic method of this compound is introduced below., Formula: C9H7NO3

Description 11:5-Methoxyindolin-2-oneTo 5-methoxyisatin (0.25 g, 1.41 mmol) in ethylene glycol (1 ml) was added hydrazine hydrate (~50%, 1.5 equiv., 0.14 ml) and potassium hydroxide (1 equiv., 79 mg). The reaction mixture was heated in microwave (150C, 5 min). Tic (EtOAc : hexane, 1:1) indicated the completion of the reaction. The reaction mixture was diluted with water, acidified to pH~1 with 2M HCI and extracted into ethyl acetate. The organic layer was dried (MgS04), filtered and volatiles were removed in vacuo. The residue was purified by ISCO Combiflash (100% DCM – 5% MeOH/DCM) to give the product as an off-white solid. The results set out below indicate the final product was the title compound D1 .1H NMR (CDCI3): 8.08 (1H, br s), 6.83 (1H, s), 6.77-6.71 (2H, m), 3.75 (3H, s), 3.50 (2H, s). 13C NMR (CDCI3): 176.3, 159.5, 135.7, 126.6, 112.5, 111.8, 109.8, 55.8, 36.5.MS: (MH+41) 205.0

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; University of Greenwich; SPENCER, John; WO2012/25726; (2012); 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. 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, A new synthetic method of this compound is introduced below., Product Details of 14192-26-8

a) Methyl 3,3-dimethyl-2-oxoindoiln-6-carboxylate To a solution of Mel (7.42 g, 3.27 ml, 52.3 mmol) in DMF (75.0 ml) was added methyl 2- oxoindoline-6-carboxylate (5 g, 26.2 mmol). Once everything was disolved NaH (60 % in mineral oil, 1.05 g, 26.2 mmol) was added and the reaction mixture was stirred for 30 minutes at room temperature. Then again NaH (60 % on mineral oil, 523 mg, 13.1 mmol) was added and stirring was continued for another hour. Again NaH (60 % on mineral oil, 523 mg, 13.1 mmol)was added and stuffing was continued for 15 hours. The reaction was quenched with 1 M aqueous HC1 solution, the mixture was extracted with ethyl acetate and the organic layers were washed with water. The combined organic layers were dried with sodium sulfate, filtered and the obtained solution was concentrated in vacuo. The resulting solid was triturated with diisopropylether, filtered and the collected solid was dried. The title compound was obtained as red solid(4.61 g)MS ESI (m/z): 220.3 [(M+H)i.1H NMR (CDC13, 300 MHz): oe = 7.98 (br s, 1H), 7.78 (dd, J=1.3, 7.8 Hz, 1H), 7.58 (d, J=1.0 Hz,1H), 7.26 (d, J=7.7 Hz, 1H), 3.92 (s, 3H), 1.42 (s, 6H).

The synthetic route of 14192-26-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BRUNNER, Daniela; HILPERT, Hans; KOLCZEWSKI, Sabine; LIMBERG, Anja; MALBERG, Jessica; PRINSSEN, Eric; RIEMER, Claus; SHANKAR, Bavani G.; STOLL, Theodor; WO2014/202493; (2014); A1;,
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. 4403-36-5, name is 2-(1,3-Dioxoisoindolin-2-yl)ethanesulfonylchloride, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 2-(1,3-Dioxoisoindolin-2-yl)ethanesulfonylchloride

Bis(4-methoxybenzyl)amine (900 mg) was dissolved in dichloromethane (20 ml) and cooled to 0C. To this solution, triethylamine (1.02 ml) was added and compound 49 (1.05 g) was added in small portions, followed by stirring at room temperature for 3 hours. After addition of water, the reaction mixture was extracted with dichloromethane. The organic layer was washed with brine and dried over magnesium sulfate. After filtration and evaporation of the solvent under reduced pressure, the resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate:n-hexane 1:1 to ethyl acetate) to give the desired compound (compound 50) (1.4 g, yield 81%). 1H-NMR (300MHz, CDCl3) delta: 3.24(2H, t, J=6.8Hz), 3.81(6H, s), 4.10-4.14(2H, m), 4.29(4H, s), 6.88(4H, d, J=8.7Hz), 7.23(4H, d, J=8.7Hz), 7.73(2H, dd, J=3.1, 5.3Hz), 7.87(2H, dd, J=3.1, 5.3Hz). Rf value (silica gel plate, developing solvent: ethyl acetate:n-hexane = 1:1): 0.24.

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 4403-36-5.

Reference:
Patent; CHUGAI SEIYAKU KABUSHIKI KAISHA; EP1634874; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 769965-95-9, The chemical industry reduces the impact on the environment during synthesis 769965-95-9, name is 5′-Fluorospiro[cyclopropane-1,3′-indolin]-2′-one, I believe this compound will play a more active role in future production and life.

A sample of 5-fluoro-siprocyclopropyloxindole (172 mg, 97 jimol) was cooled in an ice/water bath and treated with a 1.0 M solution of LAH (1.94 ml, 1.9 mmol). The reaction was stirred at room temperature for 15 minutes and then at 50 C for 3 hours and finally was cooled back down with an icelwater bath. The reaction was treated with 1 M NaOH (1.9 mL) followed by water (1.9 mL). The reaction was filtered over celite and dried over MgS04. After filtration, the solvent was removed and the crude material of 5-fluoro- siprocyclopropylindoline was used without purification.

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′-Fluorospiro[cyclopropane-1,3′-indolin]-2′-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; IRM LLC; WO2005/34848; (2005); A2;,
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. 32692-19-6, name is 5-Nitroindoline, A new synthetic method of this compound is introduced below., Safety of 5-Nitroindoline

General procedure: 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.

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; 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

Application of 667463-64-1, 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. 667463-64-1, name is 6-Bromo-1-methylindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

1-4.1 (15.0 g, 63 mmol) and hydrazine hydrate (30 mL, 618 mmol) are heated to 125 C for 72 h. To the cool reaction mixture DCM is added and extracted with water and 1 M HC1. The organic layer is dried over MgS04 and concentrated. The crystallized residue is dissolved in DCM, methanol is added and the DCM is removed in vacuo. The crystallized product is filtered by sunction and washed with cold methanol. Yield 63%, m/z 226/228 [M+H]+, rt 1.16 min, LC-MS Method V001 003.

The synthetic route of 6-Bromo-1-methylindoline-2,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRUNDL, Marc; MORSCHHAEUSER, Gerd; OOST, Thorsten; PAUTSCH, Alexander; WO2014/140078; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem