Month: November 2020

14192-26-8,Some common heterocyclic compound, 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, molecular formula is C10H9NO3, 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.

In the four 3000mL round-bottomed flask, fitted with mechanical stirring, reflux condenser, thermometer, nitrogen was added to a 1500mL round bottom flask of toluene, 240g6- methoxycarbonyl-2-oxo-indoline, chlorine 272g acetic anhydride, open stirring, temperature was raised to 80 ~ 90 , the reaction was stirred for 6 hours incubation, naturally fell off the heating 80 , 600ml of cyclohexane was added, and stirring was continued to cool down to room temperature, solid precipitated, suction filtered, the filter cake washed with cold ethanol and dried under vacuum to give 233.6g.Yield: 78%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 2-oxoindoline-6-carboxylate, its application will become more common.

Reference:
Patent; Nanjing Aide Kai Teng biological medicine limited liability company; Wang, Xuegen; He, Lingyun; Li, Xiaojing; Li, Yiwen; Yu, Yang; Guo, Liqin; (8 pag.)CN105418483; (2016); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

317-20-4, Name is 7-Fluoroisatin, 317-20-4, 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.

Step 1: Preparation of 7-fluoro-1-methyl-1H-indole-2,3-dione 7-Fluoro-1H-indole-2,3-dione (prepared according to the method of Gassman as described in U.S. Pat. No. 4,188,325, 1.0 g, 6.05 mmol), iodomethane (1.13 ml, 18.2 mmol) and potassium carbonate (1.65 g, 12.1 mmol) in DMF (15 ml) are stirred at room temperature for 24 hours. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4), and evaporated to give the title compound as an orange solid. HPLC r.t. 3.79 min; MS for C9H1FNO2 m/z 180.0(M+H)+.

Statistics shows that 7-Fluoroisatin is playing an increasingly important role. we look forward to future research findings about 317-20-4.

Reference:
Patent; Luehr, Gary W.; Jain, Rama; Renslo, Adam; Josyula, Vara Prasad Venkata Nagendra; Gordeev, Mikhail F.; US2006/30609; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 317-20-4 name is 7-Fluoroisatin, 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. 317-20-4

General procedure: A sealed tube was charged with isatin 1 (1a 147 mg, 1.0 mmol), ammonia hydrate 2 (25%, 421 mg, 3.0 mmol) and H2O2 (30%, 227 mg, 2.0 mmol) at room temperature, and then solvent DMSO (4 mL) was added. The resulting mixture was stirred at 30 C in a sealed vessel under air after 4 h, then added 50 mL water to the mixture, extracted with CH3COOC2H5 3 times (3 x 50 mL). The extract was washed with 30% NaCl solution (V/V), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (Petroleum ether/Ethyl acetate = 3:1) to yield the desired product 3a as a yellow solid (89% yield).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 7-Fluoroisatin, and friends who are interested can also refer to it.

Reference:
Article; Wang, Yu-Wei; Zheng, Lei; Jia, Feng-Cheng; Chen, Yun-Feng; Wu, An-Xin; Tetrahedron; vol. 75; 11; (2019); p. 1497 – 1503;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

480-91-1, 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 480-91-1 as follows.

General procedure: A solution of POCl3 or POBr3 (30 mmol) in anhydrous DCM (7 mL) was added dropwise to DMF or DMA (30 mmol) in anhydrous DCM (15 mL) at 0 C. The mixture was stirred for 30 min at room temperature. Then, a solution of 1H-isoindolinone 1 (2 g, 15 mmol) in anhydrous DCM (75 mL) was added to the mixture, at 0 C. Subsequently, the reaction mixture was heated at reflux for 5 h, and then after cooling, the solvent was removed at reduced pressure. Ice-water was added, and the mixture was neutralized with NaOH 5 M. The precipitate was filtered out, washed with water and dried. The residue was recrystallized from MeOH/H2O (1:1) to give the following compounds.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 480-91-1, and friends who are interested can also refer to it.

Reference:
Article; Diana, Patrizia; Martorana, Annamaria; Barraja, Paola; Montalbano, Alessandra; Carbone, Anna; Cirrincione, Girolamo; Tetrahedron; vol. 67; 11; (2011); p. 2072 – 2080;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

2058-72-2, The chemical industry reduces the impact on the environment during synthesis 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-dione, I believe this compound will play a more active role in future production and life.

General procedure: A mixture of N-methylisatin 1a (161 mg, 1 mmol, 1 equiv), phenylacetylene 2a (0.12 mL, 1 mmol, 1.2 equiv), 1-aminoanthraquinone (0.266 g, 1 mmol, 1.2 equiv) 3a, cuprous chloride (9.9 mg, 10 mol %), and copper(II) triflate (36.1 mg, 10 mol %) in dry toluene (4 mL) was refluxed at 120 C for 24 h under nitrogen atmosphere. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, filtered through a pad of neutral alumina using ethyl acetate as a solvent. The solvent was evaporated in vacuo and the residue was chromatographed on neutral alumina using gradient elution of hexane/ethyl acetate as solvent to yield compounds 4a as pink powder, 183 mg, 39% yield and 5a as violet powder, 197 mg, 42% yield.

The chemical industry reduces the impact on the environment during synthesis 5-Bromo-1-methylindoline-2,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Article; Periyaraja, Somasundharam; Shanmugam, Ponnusamy; Mandal, Asit Baran; Senthil Kumar, Thiyagarajan; Ramamurthy, Perumal; Tetrahedron; vol. 69; 14; (2013); p. 2891 – 2899;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 15362-40-0, name is 1-(2,6-Dichlorophenyl)-2-indolinone, 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. 15362-40-0

General procedure: A finely ground mixture of 5-substituted indole-3-carboxaldehyde (1 mmol) and active methylene compound (indolinone/oxindole/barbituric acid/1-(3-chlorophenyl)-3-methyl-2-pyrazolin-5-one)/2-trifluoromethylbenzaldehyde (1.2 mmol) was irradiated in microwave oven for 1-5 min. The solid product was washed with diethyl ether and purified by column chromatography to get pure products 2-5 and 11-28 except compound 3. Compound 3 was prepared by treatment of 5-substituted indole-3-carboxaldehyde with indolinone in ethanol-water in presence of NaOH (1.5 mmol).

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 15362-40-0.

Reference:
Article; Shaveta; Singh, Palwinder; European Journal of Medicinal Chemistry; vol. 74; (2014); p. 440 – 450;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 603-62-3, name is 3-Nitrophthalimide, molecular formula is C8H4N2O4, 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. 603-62-3

To a solution of potassium hydroxide (16.1 g, 286 mmol) in water (500 mL), was added 3-nitrophthalimide (25.0 g, 130 mmol) in portion at 0 C. The suspension was stirred at 0 C for 3 hrs, and then heated to 30 C for 3 hrs. To the solution, was added HCl (100 mL, 6N). The resulting suspension was cooled to 0 C for 1 hr. The suspension was filtered and washed with cold water (2 x 10 mL) to give 3-nitro-phthalamic acid as a white solid (24.6 g, 90% yield): 1H NMR (DMSO-d6) 7.69 (brs, 1H, NHH), 7.74 (t, J = 8 Hz, 1H, Ar), 7.92 (dd, J = 1, 8 Hz, 1H, Ar), 8.13 (dd, J = 1, 8 Hz, 1H, Ar), 8.15 (brs, 1H, NHH), 13.59 (s, 1H, OH); 13C NMR (DMSO-d6) 125.33, 129.15, 130.25, 132.54, 136.72, 147.03, 165.90, 167.31.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 603-62-3, its application will become more common.

Reference:
Patent; CELGENE CORPORATION; CHAMBERLAIN, Philip; CATHERS, Brian, E.; LOPEZ-GIRAONA, Antonia; (672 pag.)WO2015/200795; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 774-47-0, name is 5,6-Difluoroindoline-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. 774-47-0

5-Fluoro-6-methylthioindole-2,3-dione Sodium thiomethoxide (5.93 g, 84.6 mmol) was added to a solution of 5,6-difluoroindole-2,3-dione (7.75 g, 42.3 mmol) in dimethylformamide (400 mL). The reaction was stirred at room temperature for 1 h, then poured onto ice (2 L). The resulting solid was collected by filtration, washed with water and dried at 40 C. under vacuum to give a brown solid (3.12 g, 35%): mp 296 C.; C9H6F1NO2S requires: C, 51.18; H, 2.86; N, 6.63; S, 15.18%. Found C, 50.95; H, 2.85; N, 6.58; S, 15.35%; IR numax (Nujol)/cm-1 3285, 2925, 2854, 1760, 1714, 1611, 1465 and 1036; NMR deltaH (400 MHz, DMSO-d6) 2.58 (3H, s), 6.71 (1H, d, J 6.0 Hz), 7.38 (1H, d, J 9.0 Hz), 11.02 (1H, brs).

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 774-47-0.

Reference:
Patent; Vernalis Research Limited; US6380238; (2002); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

883-44-3, Adding some certain compound to certain chemical reactions, such as: 883-44-3, name is 2-(3-Hydroxypropyl)isoindoline-1,3-dione, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 883-44-3.

Step 2. Preparation of 3-(l,3-dioxoisoindolin-2-yl)propanal A mixture of 2-(3-hydroxypropyl)isoindoline-l,3-dione (2.0 g, 8.76 mmol) and IBX (8.2 g, 29.27 mmol) in 60 mL EA was refluxed for 2 h. The mixture was filtered and filtrate was concentrated to afford 3-(l,3-dioxoisoindolin-2-yl)propanal (2.0 g , yield: 100%) as white solid. NMR (500 MHz, CDC13): delta 9.82 (s, 2H), 7.84-7.86 (m, 2H), 7.72-7.74 (m, 2H), 4.04 (t, J = 7.0 Hz, 2H), 2.87-2.89 (m, 2H) ppm. MS (ESI): m/z 553.7 [M+l]+.

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 883-44-3.

Reference:
Patent; EPIZYME, INC.; CHESWORTH, Richard; KUNTZ, Kevin, Wayne; OLHAVA, Edward, James; PATANE, Michael, A.; WO2012/82436; (2012); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

324-03-8, Adding some certain compound to certain chemical reactions, such as: 324-03-8, name is 6-Fluoroindoline-2,3-dione, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 324-03-8.

Example 125 3-Cyclopentyl-2-(6-fluoro-2-oxo-2,3-dihydro-indol-1-yl)-N-thiazol-2-yl-propionamide A stirred suspension of sodium hydride (60% dispersion in oil, 290 mg) in N,N-dimethylformamide at 0 C. was treated with a solution of 6-fluoro-1H-indole-2,3-dione (1.0 g) in N,N-dimethylformamide (total volume, 20 mL). The reaction mixture was stirred for 30 min at 0 C. and then 2-bromo-3-cyclopentyl-propionic acid methyl ester (prepared as in Example 1, 1.71 g) was added and it was stirred for 1 h at 0 C. It was then slowly allowed to warm to room temperature and stirred for another 3 h at room temperature. After this time, the reaction mixture was diluted with water and extracted with methylene chloride (3*10 mL). The organic layers were combined and dried over sodium sulfate, filtered and the filterate concentrated in vacuo. The crude material was purified by column chromatography (silica gel, 5% ethyl acetate/hexanes) to afford 3-cyclopentyl-2-(6-fluoro-2,3-dioxo-2,3-dihydro-indol-1-yl)-propionic acid methyl ester (1.0 g, 52%).

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 324-03-8.

Reference:
Patent; Kester, Robert Francis; US2012/142705; (2012); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem