Tag: M.W=100-200

61-70-1, 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. 61-70-1, name is 1-Methylindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: An oven-dried reflux tube equipped with a magnetic stir bar and a Teflon stopcock was charged with aryl halide (1 mmol), oxindole (1 mmol),potassium carbonate (1.1 mmol), catalyst nanoparticles (0.05 mmol)and 1,4-dioxane (2 ml) and heated at 70 C. The mixture was vigorously stirred under these reaction conditions and completion of the reaction was monitored by TLC (EtOAc: n-hexane, 25:75). After completion of the reaction, the reaction mixture was cooled to room temperature, the magnetic nanoparticles of the catalyst were collected using a magnet. Ethyl acetate (5 mL) and water (10 mL)were added to the mixture in the next step. The aqueous layer was furtherextracted by ethyl acetate (2*5 mL). The combined organic layerswere washed with saturated brine, dried over CaCl2, filtered, and concentrated to give a residue which was purified by recrystallization from ethanol and water or by column chromatography on silica gelusing EtOAc: n-hexane, 1:7.

The synthetic route of 61-70-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Moghaddam, Firouz Matloubi; Tavakoli, Ghazal; Latifi, Fatemeh; Saeednia, Borna; Catalysis Communications; vol. 75; (2016); p. 37 – 41;,
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222036-66-0, A common compound: 222036-66-0, name is 5-Aminoisoindolin-1-one, belongs to indolines-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

5-Aminoisoindolin-1-one (5.92 g, 40 mmol) was added to a mixed solvent of concentrated hydrochloric acid/glacial acetic acid (13.3/4.0 mL), and cooled in an ice bath. A solution of sodium nitrite (3.04 g, 28 mmol) in water (4.4 mL) was added dropwise, and stirred at low temperature for 30 minutes. At the same time, glacial acetic acid was added in another flask and purged with sulfur dioxide until saturation. Thereto was added cuprous chloride (0.99 g, 10 mmol), and continuously purged with sulfur dioxide under stirring until the solid was almost completely dissolved. Diazonium salt solution prepared above was added dropwise slowly, and stirred at low temperature for half an hour and then at room temperature for 1 hour. The resulting mixture was extracted with dichloromethane, washed with water, and dried to give 1-oxoisoindoline-5-sulfonyl chloride (8.33 g). Yield: 90percent. MS m/z[ESI]: 232.0[M+1].

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-Aminoisoindolin-1-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Centaurus BioPharma Co., Ltd.; Chai Tai Tianqing Pharmaceutical Group Co., Ltd.; Lianyungang Runzhong Pharmaceutical Co., Ltd.; XU, Xinhe; SHEN, Yu; XIAO, Dengming; LUO, Hong; PENG, Yong; HAN, Yongxin; ZHANG, Aiming; YANG, Ling; (51 pag.)EP3257857; (2017); A1;,
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Adding a certain compound to certain chemical reactions, such as: 32372-82-0, name is Isoindoline hydrochloride, belongs to indolines-derivatives compound, 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 32372-82-0, 32372-82-0

General procedure: To a solution of 10 (371 mg, 1.00 mmol) in DMF (5 mL) was added EDC (195 mg, 1.02 mmol), and the resulting mixture was stirred at room temperature for 1 h. Then, to the reaction mixture stirred under ice-cooling was added 12n (192 mg, 1.04 mmol) and N,N-diisopropylethylamine (0.180 mL, 1.06 mmol), and the mixture was stirred at 0 C for 1 h. To the reaction mixture was added 1-(2-aminoethyl)pyrrolidine (0.140 mL, 1.12 mmol), HOBt (174 mg, 1.14 mmol), and EDC (220 mg, 1.15 mmol), and the resulting mixture was stirred at room temperature for 6 h. The reaction mixture was diluted with EtOAc, and the organic layer was washed with H2O, saturated aqueous NaHCO3, and brine, and dried over Na2SO4. The insoluble material was filtered off, and the solution was concentrated under reduced pressure. The residue oil was purified by NH silica gel column chromatography (hexane/EtOAc = 50:50 to 0:100) to afford 14n (497 mg, 83%) as a colorless solid.

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, Isoindoline hydrochloride, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Nakao, Akira; Suzuki, Hiroko; Ueno, Hiroaki; Iwasaki, Hiroshi; Setsuta, Tomofumi; Kashima, Akiko; Sunada, Shinji; Bioorganic and Medicinal Chemistry; vol. 23; 15; (2015); p. 4952 – 4969;,
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59-48-3, 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 59-48-3 as follows.

A solution of 2-indole ketone (5 g, 37.6 mmol ) in H2SO4 (50 mL) was stirred at 0 C for 30 min, then a solution of KNO3 (3.04 g, 30 mmol ) in H2SO4 (5 mL) was added slowly, and then the mixture was stirred for 15 min. The mixture was poured in ice water, and the product was precipitated from solution, collected by suction filtration, washed with methanol and dried to give 4.5 g as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) delta: 11.04 (s, 1H), 8.15 (dd, J = 8.6, 2.3 Hz, 1H), 8.09 (d, J = 2.2 Hz, 1H), 6.98 (d, J = 8.6 Hz, 1H), 3.64 (s, 2H); 13C NMR (100 MHz, DMSO-d6) delta: 177.0, 150.7, 142.2, 127.5, 125.3, 120.4, 109.4, 36.0.

According to the analysis of related databases, 59-48-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Han, Weina; Huang, Jian; Jiang, Jin; Ruhan, A.; Wang, Jinhui; Yao, Dahong; Bioorganic and medicinal chemistry letters; vol. 30; 17; (2020);,
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317-20-4, A common compound: 317-20-4, name is 7-Fluoroisatin, belongs to indolines-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

N,N-dimethylformamide (540.0 mL, 6980 mmol, 100 mass%) was added to a 2-L ChemGlass reactor equipped with a mechanical agitator, a temperature probe, and a cooling/heating circulator. Next, 7-fluoroindoline-2,3-dione (135.0 g, 817.6 mmol, 100 mass%) was added at 25 C and dissolved to form a dark red solution. The charging ports and the beaker that contained the 7-fluoroindoline-2,3-dione were washed with N,N-dimethylformamide (135.0 mL, 1750 mmol, 100 mass%) and the rinse solution was poured into the reactor. Next, cesium carbonate 60-80 mesh (203.66 g, 625.05 mmol, 100 mass%) was added portion-wise to the reaction mixture. The addition was exothermic and the temperature of the reaction mixture increased from 20 to 25.5 C. The color of the reaction mixture changed from a dark red solution to a black solution. The reactor jacket temperature was set to 0 C. Next, iodomethane (56.5 mL, 907 mmol, 100 mass%) was added slowly via an additional funnel at ambient temperature, (iodomethane temperature) while maintaining the batch temperature at less than 30 C. Upon stirring, the reaction was exothermic, reaching a temperature of 29.3 C. The batch temperature decreased to 26.3 C after 85% of iodomethane was added, and the reaction mixture turned from black to an orange. After the addition of the iodomethane was completed, the jacket temperature was raised to 25.5 C. The reaction mixture was stirred at 25 C for 2 hrs. The reddish orange-colored reaction mixture was transferred to a 1 L Erlenmeyer flask. The reaction mixture was filtered through a ceramic Buchner funnel with a No.1 Whatman filter paper to remove solid CS2CO3 and other solid by-products. In addition to a light-colored powder, there were yellow to brown colored rod-shaped crystals on top of the cake, which were water soluble. The filtrate was collected in a 2-L Erlenmeyer flask. The solids cake was washed with N,N-dimethylformamide (100.0 mL, 1290 mmol, 100 mass%). The DMF filtrate was collected in a 2-L Erlenmeyer flask. To a separate 5-L ChemGlass reactor was charged water (3000.0 mL, 166530 mmol, 100 mass%). Next, 1.66 g of 7-fluoro-l-methylindoline-2,3-dione was added as seed to the water to form an orange colored suspension. The DMF filtrate was charged to the 5-L reactor slowly while maintaining the batch temp, at less than 29 C over a period of 60 min. Stirring was maintained at 290 rpm. The orange solids precipitated instantly. The 2-L Erlenmeyer flask was rinsed with N,N-dimethylformamide (55.0 mL, 711 mmol, 100 mass%) and charged to the 5-L reactor. The slurry was cooled to 25 C and agitated at 200 rpm for 12 hrs. The mixture remained as a bright orange-colored suspension. The slurry was filtered over a No. l Whatman filter paper in a 9 cm diameter ceramic Buchner funnel to a 4L Erlenmeyer flask to provide a bright orange-colored cake. The cake was washed with 1200 mL of water via rinsing the 5000 mL reactor (400 mL x 2), followed by 300 mL of deionized water introduced directly on the orange cake. The wet cake was dried under suction for 40 min at ambient temperature until liquid was not observed to be dripping from the cake. The cake was introduced into a vacuum oven (800 mbar) with nitrogen sweeping at ambient temperature for 1 hr, at 40-45 C for overnight, and at 25 C for 1 day to provide 7-fluoro-l-methylindoline-2,3-dione (Q, 130.02 g, 725.76 mmol, 100 mass%, 88.77% yield) as a bright orange-colored solid. NMR (400 MHz, DMSO- de) delta 7.57 (ddd, J=12.0, 8.5, 1.0 Hz, 1H), 7.40 (dd, J=7.3, 1.0 Hz, 1H), 7.12 (ddd, J=8.5, 7.5, 4.0 Hz, 1H), 3.29 (d, J=3.0 Hz, 3H). 13C NMR (101 MHz, DMSO-de) delta 182.3, 158.2, 148.8, 146.4, 137.2, 125.9, 124.3, 120.6, 28.7.

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, 7-Fluoroisatin, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; CARRASQUILLO, Ronald; GENG, Peng; HUANG, Eric C.; KATIPALLY, Kishta; LEE, Andrew; MUDRYK, Boguslaw; QIAN, Xinhua; RAZLER, Thomas M.; WANG, Jianji; WEI, Carolyn S.; WISNIEWSKI, Steven R.; ZHU, Ye; (79 pag.)WO2018/118830; (2018); A1;,
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The chemical industry reduces the impact on the environment during synthesis 603-62-3, name is 3-Nitrophthalimide, I believe this compound will play a more active role in future production and life. 603-62-3

4-Nitroisoindoline (1): To a solution of 4-nitroisoindoline-l,3-dione (1.0 g, 5.2 mmol) in dry THF (20 mL) was added 1M borane solution in THF (21.0 mL, 20.8 mmol) at 0 C and then heated to 80-85 C for 12 h. The reaction mixture was treated with MeOH (2 mL) and 6N HC1 (5 mL) and refluxed for 1 h. The reaction mass was brought to room temperature and volatiles were removed under reduced pressure. The residue was dissolved in EtOAc (50 mL) and basified with saturated NaHC03 (10 mL). Organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 1 (500 mg, 59%) as white solid. 1H NMR (500 MHz, DMSO-d6): delta 4.15 (s, 2H), 4.45 (s, 2H), 7.49 (t, J = 8.0 Hz, 1H), 7.71 (d, J = 8.0 Hz, 2H), 8.02 (d, J = 7.5 Hz, 1H).

The chemical industry reduces the impact on the environment during synthesis 603-62-3. I believe this compound will play a more active role in future production and life.

Reference:
Patent; CELGENE AVILOMICS RESEARCH, INC.; ALEXANDER, Matthew David; MCDONALD, Joseph John; NI, Yike; NIU, Deqiang; PETTER, Russell C.; QIAO, Lixin; SINGH, Juswinder; WANG, Tao; ZHU, Zhendong; WO2014/149164; (2014); A1;,
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59-48-3, A common heterocyclic compound, 59-48-3, name is Indolin-2-one, molecular formula is C8H7NO, 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.

5-Bromo-2-Oxindole 2-Oxindole (1.3 g) in 20 mL acetonitrile was cooled to -10 C. and 2.0 g N-bromosuccinimide was slowly added with stirring. The reaction was stirred for 1 hour at -10 C. and 2 hours at 0 C. The precipitate was collected, washed with water and dried to give 1.9 g (90% yield) of the title compound.

The synthetic route of 59-48-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sugen. Inc.; US2003/100555; (2003); A1;,
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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 118-29-6 as follows. 118-29-6

200 mL of sulfuric acid were cooled to 0 0C. 48 g of 2,3,3 – trimethylindolenine were added to the sulfuric acid followed by the addition of 54 g of N-hydroxymethyl-phthalimide. The reaction mixture was stirred at room temperature for 7 days. The reaction mixture then was added to 500 g of crushed ice in a 2000-mL conical flask immersed in ice-salt bath. A solution of about 225 g of sodium hydroxide in 500 mL of water was cooled to 10 0C and then added dropwise to the magnetically stirred mixture in the conical flask. A white precipitate starts to form after addition of about half of the solution of sodium hydroxide. Addition of the sodium hydroxide is continued until the pH of the reaction mixture is strongly basic (pH > 12). The white solid is then filtered, washed with water (3×100 mL) and air- dried on a Buchner funnel for about 1 hour. The solid is then transferred to a 1000- mL one -neck round bottom flask, 300 mL of acetone is added and the mixture is stirred under reflux for 30 min. The flask is then cooled to 10 0C and the white product is filtered with suction on a Buchner funnel, washed with acetone (1 x50 mL), and air dried.The yield of the pure product is 70-75% (67-7O g). NMR: (DMSO-d6, 300 MHz) delta 1.33 (s, 6H, 2xCH3), 2.31 (s, 3H, CH3), 4.91 (s, 2H, CH2), 7.32 (dd, 3JH-H =8.7 Hz, 5Jn-H – 1.2 Hz, IH), 7.48 (dd, 5JH-H = 8.7 Hz, IH), 7.51 (dd, 5JH-H = 1.2 Hz, IH, 7.9-8.1 (m, 4H).; 6.1 2-(2, 3, 3-Trimethyl-3H-indol-5-ylmethyl)-isoindole-l, 3-dione, 1Sulfuric acid (420.0 mL, 7.879 mol; Sigma-Aldrich) was placed to the 1 L one -neck, round-bottom flask equipped with magnetic stirrer. The flask was cooled in ice-water bath and 2,3,3-trimethyl-3H-Indole, (100.0 g, 0.6280 mol; Sigma-Aldrich) was added to the sulfuric acid by drops during 45 min with stirring. The reaction mixture becomes a very viscous upon addition of 2,3,3-trimethyl-3H-indole, so stirring plate with adequate power and large magnetic stir bar is required. When addition of 2,3,3-trimethyl-3H-Indole was completed the ice bath was removed and 2- (hydroxymethyl)-lH-Isoindole-l,3(2H)-dione, (112 g, 0.632 mol; Aldrich) was added to the reaction mixture at once. The flask was closed with a glass stopper and the stirring was continued for 168 hours at room temperature. In about 12 hours all solid, 2-(hydroxymethyl)-lH-Isoindole-l,3(2H)-dione dissolved and clear brown solution formed.After 168 hours the content of the flask was poured into 4-L conical flask containing 1 kg of ice. The 4-L flask was immersed in ice-salt bath, equipped with mechanical stirrer. A cooled to 10 0C solution of 550g of NaOH in 1.5 L of water was slowly added to the reaction mixture at such rate that temperature inside of flask didn’t increase higher than 20 0C. The addition takes about 1 hour. The white precipitate formed was filtered on Buchner funnel with suction and dried on air for 12 hours.The crude 2-(2,3,3-Trimethyl-3H-indol-5-ylmethyl)-isoindole-l,3-dione was placed in conical 2 L flask, 1 L of acetone was added and the mixture was magnetically stirred with heating until acetone start to boil. The heating was reduced to maintain a very gentle boiling and the content of the flask was stirred for additional 10 min. Flask was cooled using ice-water bath and the separated crystals were filtered, washed with acetone and dried. The yield of the first crop with m.p. = 186-187 0C was 82 g. The mother liquor was reduced in volume to about 300 mL and cooled at -10 0C overnight. The separated crystals were filtered, washed with acetone and dried. The yield of the second crop with m.p. = 184-185 0C was 45 g. The total yield was 126 g (63% of theoretical).Analytical Results for 1:M.p. = 186-187 0C1H NMR (CDCl3, 300 MHz) delta 1.28 (s, 6H), 2.25 (s, 3H), 4.87 (s, 2H), 7.38- 7.45 (m, 3H), 7.68-7.71 (m, 2H), 7.83-7.86 (m, 2H). 13C NMR (CDCl3, 75 MHz) delta 15.4, 23.0, 41.7, 53.7, 119.8, 122.0, 123.3, 128.4,132.2, 133.3, 133.9, 146.1, 153.5, 168.0, 188.5.

According to the analysis of related databases, 118-29-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL; WO2008/157762; (2008); A2;,
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20876-36-2,Some common heterocyclic compound, 20876-36-2, name is 5-Aminoindolin-2-one, molecular formula is C8H8N2O, 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.

A THF (20 mL) solution of 5-aminoindolin-2-one (200 mg, 1.3 mmol) and di-t-butyl dicarbonate (300 mg, 1.4 mmol) at rt under N2, was treated with Et3N (0.37 mL, 2.7 mmol). The stirring was continued at rt overnight; the reaction mixture was concentrated under reduced pressure, taken into DCM and washed (H2O 2x, brine). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Trituration with hexanes provided the title compound as a white solid (260 mg, 77 percent). 1H NMR (400 MHz, CDCl3) delta ppm 7.43 (br. s., 2 H), 7.07 (dd, J=8.84, 1.26 Hz, 1 H), 6.77 (d, J=8.59 Hz, 1 H), 6.39 (br. s., 1 H), 3.52 (s, 2 H), 1.52 (s, 9 H); MS ESI 249.0 (80) [M + H]+, calcd for [C13H16N2O3 + H]+ 249.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 20876-36-2, its application will become more common.

Reference:
Patent; UNIVERSITY HEALTH NETWORK; WO2009/79767; (2009); A1;,
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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 59-48-3 as follows. 59-48-3

5-Nitro-2-oxindole 2-Oxindole (6.5 g) was dissolved in 25 mL concentrated sulfuric acid and the mixture maintained at -10 to -15 C. while 2.1 mL of fuming nitric acid was added dropwise. After the addition of the nitric acid the reaction mixture was stirred at 0 C. for 0.5 hr and poured into ice-water. The precipitate was collected by filtration, washed with water and crystallized from 50% acetic acid. The crystalline product was then filtered, washed with water and dried under vacuum to give 6.3 g (70%) of 5-vitro-2-oxindole.

According to the analysis of related databases, 59-48-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sugen, Inc.; US6878733; (2005); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem