Month: April 2021

Application of 13220-46-7,Some common heterocyclic compound, 13220-46-7, name is 4-Methylindolin-2-one, molecular formula is C9H9NO, 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 21 3-[2,4-Dimethyl-5-(4-methyl-2-oxo-1,2-dihydroindol-3-ylidene-methyl)-1H-pyrrol-3-yl]-propionic acid 3-(2-Carboxyethyl)-2,4-dimethyl-5-formylpyrrole (97.5 mg), 74 mg 4-methyl-2-oxindole, and 75 muL piperidine in 3 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 of aqueous hydrochloric acid. The precipitate was filtered, washed with water to pH 6 and dried in a vacuum oven overnight to give 60 mg (37%) of the title compound as a green solid. 1H-NMR (360 MHz, DMSO-d6): delta 13.41 (s, br, 1H, NH-1′), 12.03 (s, br, 1H, COOH), 10.72 (s, br, 1H, NH-1), 7.50 (s, 1H, H-vinyl), 7.01 (t, J=7.82 Hz, 1H, H-6), 6.79 (d, J=7.82 Hz, H-5), 6.74 (d, J=7.82 Hz, 1H, H-7), 2.64 (t, J=7.76 Hz, 2H, CH2CH2COOH), 2.56 (s, 3H, CH3), 2.34 (t, J=7.76 Hz, 2H, CH2CH2COOH), 2.29 (s, 3H, CH3), 2.18 (s, 3H, CH3); MS m/z (relative intensity, %) 325 ([M+1]+, 100).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Methylindolin-2-one, its application will become more common.

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

Application of 118289-55-7, 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 118289-55-7 as follows.

100.0 g of 6-Chloro-5-(2-chloroethyl) oxindole, 133.39 g of 3-(l-Piperazinyle)- 1,2-benzisothiazole hydrochloride, 105.94 g of sodium carbonate and 1500 mL of water were taken in round bottom flask and heated to 1000C to HO0C for 24-26 hours. The reaction mixture was cooled and maintained for 30 min. The solid was filtered and washed with water. The wet solid was further slurried with water followed by adjusting the pH of the reaction mass with dilute acetic acid to 6.0 to 7.5 and maintain the reaction mass for 1-2 hours. The solid was filtered and washed with water. The wet solid was treated with isopropanol 1100 mL in round bottom flask and heated at 750C to 850C for 2 hours. The reaction mixture was cooled, the obtained solid was filtered and washed with isopropanol. The wet solid was dried at 6O0C to 650C for 8-10 hours to obtain crude Ziprasidone base.

According to the analysis of related databases, 118289-55-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CADILA HEALTHCARE LIMITED; SHAH, Niraj, Shyamlal; DWIVEDI, Shriprakash, Dhar; WO2010/73255; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 446292-07-5,Some common heterocyclic compound, 446292-07-5, name is (R)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)amino)propyl)isoindoline-1,3-dione, molecular formula is C21H21N3O5, 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.

100 g (i?)-2-(2-hydroxy-3-(4-(3-oxo-morpholino) phenyl amino) propyl) isoindoline-l,3-dione of Formula (F) and MDC (1000 ml) were added to RBF at 25C to 35C and heated to 40C to 45C. Further, 61 g Nu,Nu-Carbonyl diimidazole (CDI) and 0.5 g DMAP were added and stirred for 3-4 hours. Excess MDC was evaporated under reduced pressure. The reaction mass was cooled to 25C to 35C followed by addition of dilute HCl solution and stirred for 1 hour and finally filtered and washed with 2 x 200 ml water to afford title compound as (S)-2-((2-oxo 3-(4-(3-oxo- mo holno)phenyl)oxazolidin-5-yl)methyl)isoindoline-l,3-dione of Formula (I).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)amino)propyl)isoindoline-1,3-dione, its application will become more common.

Reference:
Patent; CADILA HEALTHCARE LIMITED; DWIVEDI, Shriprakash, Dhar; PRASAD, Ashok; PAL, Daya, Ram; SHARMA, Mukul, Hari, Prasad; JAIN, Kuldeep, Natwarlal; PATEL, Naitik, Bharatbhai; WO2013/98833; (2013); 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 24566-79-8 as follows. Computed Properties of C14H16BrNO2

To a stirred solution of compound 3-i (6.39 g, 20.3 mol) in DMF (60 mL) was added potassium thioacetate (2.78 g, 34.3 mmol) portion wise and stirred for 20 mm at room temperature. After complete addition, the reaction mixture was stirred at room temperature for 30 mm. Reaction progress was monitored by TLC; after completion the reaction mixture was quenched with ice-cold water (250 mL) and stirred for 1 h. The resultant precipitated was filtered, washed with water (100 mL) and dried in vacuo to afford 4-i as an off-white solid(5.8 g, 93.5%). LCMS: 306.20 (M+1).

According to the analysis of related databases, 24566-79-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CV6 THERAPEUTICS (NI) LIMITED; SPYVEE, Mark; LADNER, Robert, D.; (340 pag.)WO2018/98207; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 20870-90-0, 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. 20870-90-0, name is 5-Bromo-1-methyl-2-oxoindoline, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: To a precooled stirring suspension of NaH (6.0 mmol, 0.144 g) in THF (10 mL) at -78 C was added a solution of N-methyloxindole (5a) (6.0 mmol, 0.883 g) in THF (10 mL) dropwise. Then the cooling bath was removed and stirring continued for 5 min (till the formation of clear solution). Then the reaction mixture was again cooled to -78 C and a solution of methyl 3-hydroxy-2-methylene-3-phenylpropanoate (6a) (2.0 mmol, 0.468 g) in THF (15 mL) was added dropwise over 30 min. After stirring for further 10 min at the same temperature, the cooling bath was removed and the reaction was quenched with saturated NH4Cl solution and extracted with EtOAc (3¡Á30 mL). Combined organic layer was dried over anhydrous Na2SO4.. Solvent was removed and the crude obtained was purified by column chromatography(10-15% EtOAc in hexanes) provided title compound (7a) (0.539 g) as a colorless solid in 84% yield.

The chemical industry reduces the impact on the environment during synthesis 5-Bromo-1-methyl-2-oxoindoline. I believe this compound will play a more active role in future production and life.

Reference:
Article; Basavaiah, Deevi; Lingam, Harathi; Babu, Thelagathoti Hari; Tetrahedron; vol. 74; 19; (2018); p. 2306 – 2313;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, 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. Quality Control of tert-Butyl 5-bromoisoindoline-2-carboxylate

0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of 5- bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at -780C under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 mul; 1.2 equiv.) was added and stirred at -780C for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia / DCM gave 111 mg of 5-(4-hydroxy-1-methyl- piperidin-4-yl)-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyi ester as a colourless oil.

The synthetic route of 201940-08-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2008/44041; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 32692-19-6, name is 5-Nitroindoline, molecular formula is C8H8N2O2, 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. Computed Properties of C8H8N2O2

Reference Example 49 7-bromo-5-nitro-1H-indoline 5-nitro-1H-indoline (2.0 g) was dissolved in acetic acid (15.0 mL), bromine (1.0 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water, and this was neutralized with a 1 mol/L aqueous sodium hydroxide solution. The produced crystal was filtered and washed with water, and the resulting crystal was then dried under reduced pressure to obtain the title compound (3.3 g). 1H NMR (CDCl3) delta (ppm): 3.27(2H,t), 3.86(2H,t), 7.90(1H,s), 8.19(1H,s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 32692-19-6, its application will become more common.

Reference:
Patent; Sanwa Kagaku Kenkyusho Co., Ltd; EP2036887; (2009); 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 366452-98-4 as follows. Safety of 4-Amino-2,3-dihydro-1H-isoindol-1-one

l Synthesis of isoindolinone (25): The suspension of 2,3-dihydro-1H-isoindol-1-one 4 (0.100 gm, 0.61 mmol.) in ethyl acetate and aq. NaHCO3 solution, was added m-nitrobenzoyl chloride (0.15 mg, 0.81 mmol.) at room temperature. The reaction mixture was stirred at room temperature for 30 min, and solid separated was filtered and dried under vacuum to give 2,3-dihydro-1H-isoindol-1-one 25 (0.041 gm, 36%).

According to the analysis of related databases, 366452-98-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Jagtap, Prakash; Southan, Garry; Salzman, Andrew; Szabo, Csaba; Ram, Siya; US2002/95044; (2002); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 20870-78-4,Some common heterocyclic compound, 20870-78-4, name is 5-Bromoindolin-2-one, molecular formula is C8H6BrNO, 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 (10 g, 47 mmol), 7.4 g (61 mmol) of benzeneboronic acid, 4.0 g (3.5 mmol) of tetrakis(triphenylphosphine)palladium(0), 17 g (160 mmol) of anhydrous sodium carbonate, 100 mL of toluene and 100 mL of ethanol were refluxed for 18 hours. The mixture was vacuum filtered hot to remove insolubles. The organic layer of the filtrate was separated while hot and concentrated. The solids were collected by vacuum filtration and washed with 5 mL of ethanol. The solids were triturated with 1 N hydrochloric acid, collected by vacuum filtration, washed with water and dried under vacuum. The crude solids were triturated with dichloromethane and dried under vacuum to give 8.3 g (63% yield) of the title compound. 1H-NMR (dimethylsulfoxide-d6) delta10.00 (s, 1H), 7.20-6.80 (multiplets, 9H), 3.50 (s, 3H).

The synthetic route of 20870-78-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUGEN, Inc.; US2004/186160; (2004); 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 2058-74-4 as follows. name: 1-Methylisatin

General procedure: A solution of N-methylisatin (322 mg, 2.0 mmol), phenylacetylene (306 mg, 3.0 mmol), CuI (76 mg, 0.4 mmol), and Cs2CO3 (978 mg, 3.0 mmol) in CH3CN (4.0 mL) was stirred at room temperature for 18 h. After aqueous extractive workup and column chromatographic purification process (CH2Cl2/EtOAc, 15:1) 1a was obtained as a pale yellow solid, 347 mg (66%).1-12 Other compounds were prepared similarly,1-12 and the propargylic alcohols were used in the next hydrogenation step without further identification process.

According to the analysis of related databases, 2058-74-4, the application of this compound in the production field has become more and more popular.

Reference:
Note; Seo, Da Young; Min, Beom Kyu; Roh, Hwa Jung; Kim, Jae Nyoung; Bulletin of the Korean Chemical Society; vol. 38; 10; (2017); p. 1231 – 1234;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem