Author: tianli

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. 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. 2058-72-2

General procedure: A mixture of substituted isatin 4a-v (1 mmol), sarcosine 5 (1 mmol) and 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene)propanenitrile 6 (1 mmol) were refluxed in ethanol (5 mL). After completion of the reaction as evidenced by TLC analysis, the reaction mixture was poured into ice-water, the resulting solid was filtered off and purified by column chromatography using ethyl acetate/petroleum ether (6:4) as an eluent to afford pure spirooxindoles 7a-v.

The synthetic route of 2058-72-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Arun; Bhaskar; Balachandran; Ignacimuthu; Perumal; Bioorganic and Medicinal Chemistry Letters; vol. 23; 6; (2013); p. 1839 – 1845;,
Indoline – Wikipedia,
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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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 923590-95-8, name is 4-Bromoisoindoline hydrochloride, molecular formula is C8H9BrClN, 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. 923590-95-8

Step a To a stirred solution of 4-bromoisoindoline hydrochloride (CAS Number 923590-95-8; 0.1 g, 0.426 mmol) in l,4-dioxane:water (5: 1; 6 ml) were added phenylboronic acid (0.078 g, 0.64 mmol) and K2C03 (0.176 g, 1.279 mmol) at rt. The reaction mixture was degassed with nitrogen for 10 min. Pd(PPh3)4 (0.024 g, 0.021 mmol) was added to the reaction and reaction mixture was heated at 100C for 16 h. The resulting reaction mixture was cooled to rt and combined with 2 other batches prepared on the same scale by an identical method. The reaction mixture was poured into water (100 ml) and extracted with EtOAc (2 x 20 ml). The combined organic phase was separated, dried over Na2S04, filtered and evaporated to dryness. The residue was re-dissolved in EtOAc (2 ml) and 4M HC1 in 1,4- dioxane (0.3 ml) was added at 0C. The mixture was stirred at rt for 30 min. The excess of solvent was distilled under vaccum and residue was triturated with diethyl ether (10 ml) and EtOAc (10 ml) yielding 4-phenylisoindoline hydrochloride (0.1 g, 0.512 mmol). This material was used for the next step without further purification. LCMS: Method A, 1.731 min, MS: ES+ 196.44; NMR (400 MHz, DMSO-d6) delta ppm 9.84 (br, s, 1H), 7.42 – 7.60 (m, 8 H), 4.49 – 4.63 (m, 4 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 923590-95-8, its application will become more common.

Reference:
Patent; MISSION THERAPEUTICS LIMITED; GIBSON, Karl Richard; JONES, Alison; KEMP, Mark Ian; MADIN, Andrew; STOCKLEY, Martin Lee; WHITLOCK, Gavin Alistair; WOODROW, Michael D; (241 pag.)WO2017/158388; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

99365-40-9, These common heterocyclic compound, 99365-40-9, name is 6-Bromoindolin-2-one, 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.

a) 6-(4,4,5,5-Tetramethyl-[1 ,3,2]dioxaborolan-2- l)-1 ,3-dihydro-indol-2-one6-Bromo-1 ,3-dihydro-2H-indol-2-one (150 mg, 0.71 mmol), bis(pinacolato)diboron (233 mg, 0.92 mmol), KOAc (104 mg, 1.07 mmol) and Pd(dppf)CI2 (29 mg) in anhydrous DMF (3 mL) were heated under N2 at 90C for 16 h. The mixture was diluted with EtOAc (40 mL) and washed with water (30 mL) then brine (30 mL). The organic layer was dried (Na2S04) and concentrated in vacuo. Purification by column chromatography (MeOH-DCM gradient) gave a yellow solid (72 mg, 39%); 1H NMR (400 MHz, DMSO-d6) delta 10.38 (s, 1 H), 7.27 (dd, J=7.3, 0.9 Hz, 1 H), 7.23 (d, J=7.3 Hz, 1 H), 7.07 (s, 1 H), 3.49 (s, 2H), 1.29 (s, 12H); m/z (ES+APCI)+: 260 [M+H]+.

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 99365-40-9.

Reference:
Patent; MEDICAL RESEARCH COUNCIL TECHNOLOGY; OSBORNE, Simon; CHAPMAN, Timothy; LARGE, Jonathan; BOULOC, Nathalie; WALLACE, Claire; WO2011/101640; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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);,
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. 1168150-46-6, name is (E)-Methyl 3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate, A new synthetic method of this compound is introduced below., 1168150-46-6

General procedure: A mixture of intermediate (3a, 3b, 6a, 6b, 10a, 10b, 11a-d, and14a-g, 1.5 mmol) and methyl (E)-3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate (1.5 mmol) in methanol (10 mL) wasstirred under reflux for 5-10 h. When TLC showed the completionof the reaction, the solution was cooled to room temperature. Theprecipitate was filtered off to give a crude product, which wasrecrystallized from methanol to provide the target compounds.

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; Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang; European Journal of Medicinal Chemistry; vol. 139; (2017); p. 492 – 502;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding some certain compound to certain chemical reactions, such as: 99365-40-9, name is 6-Bromoindolin-2-one, 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 99365-40-9. 99365-40-9

Example 20: 3-Amino-6- (4-12-hydroxy-2- [5- (2-oxo-2, 3-dihydro-lH-indol-6-yl)- pyridin-2-yl]-ethylamino}-piperidin-1-yl)-4-trifluoromethyl-thieno [2, 3-b] pyridine-2- carboxylic acid amide An N2-purged suspension of 3-Amino-6-{4-[2-(5-bromo-pyridin-2-yl)-2-hydroxy- ethylamino]-piperidin-1-yl}-4-trifluoromethyl-thieno [2, 3-b] pyridine-2-carboxylic acid amide (150 mg, 0.268 mmol), bis (pinacolato) diboron (153 mg, 0.590 mmol), [1,1′- bis (diphenylphosphino) ferrocene] dichloropalladium (II)-CH2Cl2 complex (33 mg, 0.040 mmol), and potassium acetate (133 mg, 1.34 mmol) in dry DMF (4 ml) was heated at 80 C for 2.5 h. The crude reaction mixture was then added directly via syringe to a stirring, N2- purged suspension of 6-bromo-2-oxindole (65 mg, 0.295 mmol), tetrakis (triphenylphosphine) palladium (0) (47 mg, 0.040 mmol), and potassium carbonate (74 mg, 0.536 mmol) in dry DMF (6 ml) and water (2 ml) at rt. The sealed mixture was heated to 85 C for 4 h. The crude reaction was applied direcly to a Si02 column and purified (0-25% MeOH/CH2Cl2 with NH4OH). Fractions containing desired product were pooled and concentrated. The yellow residue was dissolved in 2 ml DMF and applied to a 2 mm prep plate (Merck) eluting with 10% MeOH/CH2Cl2 with 1% NH40H. The yellow product crystallized at the origin and the impurities were removed by being carried up the plate. The recovered yellow residue was dissolved in 1 ml DMF, 2 ml MeOH, 5 ml EtOAc, and 5 ml CH2C12 and crystallized by the addition of 30 ml hexanes to give 20.5 mg, 11.9% of 3-Amino-6- (4-f2-hydroxy-2- [5- (2-oxo-2, 3-dihydro-lH-indol-6-yl)-pyridin-2-yl]- ethylamino}-piperidin-l-yl)-4-trifluoromethyl-thieno [2, 3-b] pyridine-2-carboxylic acid amide product. ES+ 612. 4 m/z (MH+).

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 6-Bromoindolin-2-one.

Reference:
Patent; BOEHRINGER INGELHEIM PHARMACEUTICALS, INC.; WO2005/56562; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem