Category: indolines-derivatives

Electric Literature of 1168150-46-6, A common heterocyclic compound, 1168150-46-6, name is (E)-Methyl 3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate, molecular formula is C18H15NO4, 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.

N-methyl-2-(4-methylpiperazin-1-yl)-N-(5-amino-2-yl)acetamide (466m9,1.6mmo1) and (E) -3- (methyl group (phenyl) methylene) -2-oxo-indoline-6-carboxylate (500mg, 1.6mmol) placed in 15mL of methanol was heated to 70 C, 13h of holding, and then cooled to room temperature, washed with suction, the product of cold ethanol, and dried to give a bright yellow solid, methyl (Z)-3-((4-(N-cyclopropyl-2-(4-methylpiperazin-1-yl)acetylamino)anilino)(phenyl)methylene)-2-oxoindoline-6-carboxylate (500mg, 80%).

The synthetic route of 1168150-46-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shandong Hengli medical science and Technology Co Ltd; Luo, haoxian; Wang, aichen; (42 pag.)CN103848814; (2016); B;,
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. 25369-33-9, name is 7-Chloroindolin-2-one, This compound has unique chemical properties. The synthetic route is as follows., Formula: C8H6ClNO

To a cooled (0 C.) solution of 7-chioroindolin-2- one (1.0 g, 6.0 mmol) in TFA (11 mE) was added N-bromosuccinimide (1.0 g, 6.0 mmol) in portions. The reaction mixture was stirred at 0 C. for 6 h. The solvent was removed in vacuo and the residue was diluted with DCM (25 mE) and concentrated, followed by a similar sequence with EtOAc. The crude product was triturated with ethanol to provide the title compound as a white solid (861 mg, 58% yield). MS (ESI): mass calcd. for C8H5I3rC1NO, 244.9; mlz found, 246.0 [M+H]. ?H NMR (500 MHz, DMSO-d5) oe 10.92 (s, 1H), 7.52-7.48 (m, 1H), 7.38 (d, J=1.2 Hz, 1H),3.62 (s, 2H).

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 25369-33-9.

Reference:
Patent; Janssen Pharmaceutica NV; Ameriks, Michael K.; Laforteza, Brian Ngo; Savall, Brad M.; Wade, Warren Stanfield; Meyer, Stephen Todd; Gyuris, Mario; (39 pag.)US2018/111925; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 5332-26-3,Some common heterocyclic compound, 5332-26-3, name is 2-(Bromomethyl)isoindoline-1,3-dione, molecular formula is C9H6BrNO2, 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 solution of LiHMDS (4.54 mL, M in THF) in THF (11 mL) was added at -78C a solution of intermediate E.ii (1.0 g, 3.78 mmol) in THF (3 mL) over 10 min. After stirring for 1 h at -78C a solution of N-(bromomethyl)phthalimide (1-09 g, 1.2 eq.) in THF (4 mL) was added dropwise over 10 min. The mixture was stirred at -78C for 1 h and then at rt overnight. The resulting solution was quenched with INHCl and extracted with DCM. The combined org. layers were washed with water, dried over MgSO4, concentrated and purified by CC (Hept/EA 1 :1) to afford the title intermediate as an off- white solid (0.361 g, 43% yield).MS (ESI, m/z): 424.4 [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 2-(Bromomethyl)isoindoline-1,3-dione, its application will become more common.

Reference:
Patent; ACTELION PHARMACEUTICALS LTD; HUBSCHWERLEN, Christian; RITZ, Daniel; RUEEDI, Georg; SURIVET, Jean-Philippe; ZUMBRUNN ACKLIN, Cornelia; WO2010/41194; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 102359-00-2, A common heterocyclic compound, 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, molecular formula is C9H7NO3, 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.

After standing overnight the filtrate yielded 2 g of 5-carboxy-2-oxindole as a yellow solid. The crude dark brown product was dissolved in hot methanol, the insoluble material removed by filtration and the filtrate concentrated to give 5.6 g of 5-carboxy-2-oxindole as a brown solid. The combined yield was 97%. 1H-NMR (360 MHz, DMSO-d6) delta 12.56 (s, br, 1 H, COOH-5), 10.70 (s, 1 H, NH-1), 7.82 (dd, J=1.57, 7.79 Hz, 1 H, H-6), 7.74 (s, br, 1 H, H-4), 6.87 (d, J=7.79 Hz, 1 H, H-7), and 3.53 (s, 2 H, CH2-3). MS m/z (relative intensity, %) 178 ([M+1]+, 100).

The synthetic route of 102359-00-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sugen, Inc.; US6395734; (2002); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 19155-24-9, 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 19155-24-9 as follows.

5-bromo-1,3-dihydro-3,3-dimethyl-2H-indol-2-one 3,3-dimethyl-indol-2-one (0.65 g, 4.03 mmol) and sodium acetate (0.33 g, 4.07 mmol) were stirred in acetic acid (5 cm3) then bromine (0.66 g, 4.13 mmol) in acetic acid (5 cm3) was added drop-wise to the reaction mixture. The reaction was stirred for 50 min., and then poured into water. The mixture was basified with sodium carbonate and then extracted with ethyl acetate (*3), dried (MgSO4), filtered, and evaporated to the title compound (0.89 g, 92percent) 1H NMR (DMSO-d6) delta1.21 (s, 6H), 6.76 (d, 1H, J=8.22 Hz), 7.29 (dd, 1H, J=2.12 Hz, 8.23 Hz), 7.49 (d, 1H, J=2.03 Hz), 10.4 (s, 1H).

According to the analysis of related databases, 19155-24-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; American Home Products Corporation; Ligand Pharmaceuticals, Inc.; US6391907; (2002); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 84575-27-9,Some common heterocyclic compound, 84575-27-9, name is 7-Methoxyindoline-2,3-dione, molecular formula is C9H7NO3, 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 suspension of 7-methoxyindoline-2,3-dione (1 g, 5.6 mmol) in AcOH (5.6 mL) was added bromine (0.35 mL, 6.7 mmol) at 0 C. The mixture was allowed to stir at ambient temperature for 2 hours and then poured into ice and stirred for 30 minutes. The resulting mixture was filtered and the solids were washed with H2O to afford the title compound as an orange solid (1.3 g, 92%). MS (ESI): mass calcd. for C9H6BrNO3, 256.0; m/z found, 257.6 [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta 11.22 (s, 1H), 7.48 (d, J=1.7 Hz, 1H), 7.25 (dd, J=1.8, 0.7 Hz, 1H), 3.90 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7-Methoxyindoline-2,3-dione, its application will become more common.

Reference:
Patent; Janssen Pharmaceutica NV; Ameriks, Michael K.; Laforteza, Brian Ngo; Lebold, Terry Patrick; Ravula, Suchitra; Savall, Brad M.; Shireman, Brock T.; (70 pag.)US2018/111942; (2018); 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. 99365-40-9, name is 6-Bromoindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of 6-Bromoindolin-2-one

n-BuLi (2.5M in hexane, 158 mL, 396 mmol) was added dropwise to a stirred and cooled (-40C) suspension of 6-bromoindolin-2-one (21.0 g, 99 mmol) and i-Pr2NH (29.4 mL, 208 mmol) in dry THE (225mL) under Ar. During addition the temperature is maintained below -20C. After complete addition, the temperature was allowed to warm to 0C, then a solution of 1 ,2-dibromoethane (25.6 mL, 297 mmol) in dry THF (25 mL) was added dropwise maintaining a temperature of below 10C. After complete addition, the reaction mixture was stirred at room temperature for 1 8h. The reaction mixture was concentrated to a smaller volume (-75 mL) under reduced pressure.The residue was diluted with EtOAc (200 mL) and brine (100 mL). The biphasic mixture was then stirred vigorously. The pH of the solution was brought to a value of 5 by slowly adding 4M aqueous HCI (-50 mL). The biphasic system was filtered through a glass filter in order to remove the solids which appeard in the bisphasic system. The solids were rinsed with EtOAc (-10 mL), collected and dried on the air to give a first batch of INT-1 as a pale solid (13.99 g, 58.8 mmol, 59.3%).The filtrate layers were separated. The aqueous phase was extracted with EtOAc (2x 100 mL). The combined organic phases were washed with brine (100 mL), dried over Na2SO4 and the solvent was distilled off. The viscous dark-brown residue was stirred with EtOAc (25 mL) for 5 mm at rt. The suspension was then slowly diluted with heptane (75 mL) while stirring which again resulted in solids which were filtered off, rinsed with heptane (10 mL), collected and air-dried to give a second batch of INT-1 (1)as a brown solid (6.04 g, 25.4 mmol, 25.6%).LCMS: calculated for [M+H]: 238/240, found: 238/240, mono-Br isotope pattern observed.

The synthetic route of 99365-40-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GRUeNENTHAL GMBH; NARDI, Antonio; JAKOB, Florian; KONETZKI, Ingo; CRAAN, Tobias; HESSLINGER, Christian; DOODEMAN, Robin; (0 pag.)WO2016/8593; (2016); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 17564-64-6, 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. 17564-64-6 name is 2-(Chloromethyl)isoindoline-1,3-dione, 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.

General procedure: The initial carbonyl compound (50 mmol) was dissolved/suspended in ethanol (50 mL) and magnetically stirred with thiosemicarbazide (50 mmol) and catalytic amounts of acetic acid for 8-24 h at room temperature. The obtained thiosemicarbazone was filtered, washed with appropriate solvent (n-hexane, petroleumether or diethyl ether) and dried under vacuum. The intermediate thiosemicarbazone (50 mmol) reacted with ethyl bromoacetate (50 mmol), in methanol (50 mL) and sodium acetate (50 mmol) at room temperature under magnetic stirring for 24 h. The resulting 4-thiazolidinone was poured on ice, filtered or extracted with chloroform (3 x 100 mL) and purified by column chromatography (SiO2, ethyl acetate/n-hexane). Then, the obtained thiazolidinone (50 mmol) was dissolved/suspended in 50 mL of anhydrous acetone in the presence of anhydrous potassium carbonate (50 mmol), and reacted with equimolar amounts of 4-nitrobenzyl bromide, 1-(chloromethyl)naphthalene and N-(chloromethyl)phthalimide for 24-48 h. The product was poured on ice, filtered or extracted with chloroform (3 x 50 mL) and purified by column chromatography (SiO2, ethyl acetate/n-hexane) in order to obtain the title compoundsin high yields. 7.1.63 2-((2-(2-(2-Methylcyclopentylidene)hydrazono)-4-oxothiazolidin-3-yl)methyl)isoindoline-1,3-dione (11C) White powder, mp 158-162 C, 83% yield; 1H NMR (400 MHz, CDCl3): delta 1.14-1.17 (d, J = 10 Hz, 3H, CH3), 1.28-1.31 (m, 2H, cyclopentane), 1.83 (bs, 1H, cyclopentane), 1.98-2.02 (m, 1H, cyclopentane), 2.25-2.30 (m, 1H, cyclopentane), 2.48-2.54 (m, 2H, cyclopentane), 3.83 (s, 2H, CH2, thiazolidinone), 5.71 (s, 2H, ArCH2), 7.76-7.77 (m, 2H, Ar), 7.86-7.88 (m, 2H, Ar). 13C NMR (100 MHz, CDCl3): delta 16.9, 22.5, 30.3, 32.5, 33.7, 39.6, 45.1, 123.6, 131.7, 134.3, 157.9, 166.7, 171.0, 182.3.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(Chloromethyl)isoindoline-1,3-dione, and friends who are interested can also refer to it.

Reference:
Article; De Monte, Celeste; Carradori, Simone; Bizzarri, Bruna; Bolasco, Adriana; Caprara, Federica; Mollica, Adriano; Rivanera, Daniela; Mari, Emanuela; Zicari, Alessandra; Akdemir, Atilla; Secci, Daniela; European Journal of Medicinal Chemistry; vol. 107; (2016); p. 82 – 96;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 32372-82-0, name is Isoindoline hydrochloride, molecular formula is C8H10ClN, 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. Recommanded Product: 32372-82-0

a. 2-chloro-4-(2,3-dihydro-1H-isoindol-2-yl)-pyrimidine A mixture of 0.5 g (3.35 mmol) of 2,4-dichloro-pyrimidine, 0.5 g (3.2 mmol) of 2,3-dihydro-1H-isoindol-hydrochloride and 0.6 ml (3.4 mmol) of N-ethyl-diisopropylamine is stirred in 40 ml dichloromethane for 3 hours. Then the mixture is concentrated by evaporation, the residue is distributed in ethyl acetate/water, the organic phase is separated off and concentrated by evaporation. Yield: 0.4 g (55% of theory), Rf value: 0.4 (silica gel; dichloromethane/ethanol=19:1)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 32372-82-0, its application will become more common.

Reference:
Patent; Boehringer Ingelheim Pharma KG; US2003/55263; (2003); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 41663-84-7, A common heterocyclic compound, 41663-84-7, name is 2-Methyl-5-nitroisoindoline-1,3-dione, molecular formula is C9H6N2O4, 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 4 To a reaction vessel containing dimethylacetamide (25 ml) were added 4-nitro-N-methylphthalimide (0.50 g, 0.00243 mol), biphenyl (0.204 g, 0.00132 mol) and sodium hydrogen sulfide (0.14 g, 0.0025 mol). The reaction was allowed to proceed at 70 C. for 24 hours. Samples of the reaction mixture were taken and examined by HPLC methods. A yield of 16.3% 4,4’bis(N-methylphthalimide)sulfide was indicated. The isolated yield was 15% (0.035 g).

The synthetic route of 41663-84-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; General Electric Company; US4625037; (1986); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem