Author: tianli

The chemical industry reduces the impact on the environment during synthesis 446292-07-5, name is (R)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)amino)propyl)isoindoline-1,3-dione, I believe this compound will play a more active role in future production and life. 446292-07-5

Add 28 kg of rivaroxaban intermediate IV to 280 L of absolute ethanol, and add 36.5 kg of 40% methylamine solution.After refluxing for 1 h, the temperature was lowered to 50-60 C.Add 6N hydrochloric acid to adjust the pH to 2~3,Cool down to room temperature, centrifuge,Drying the filter cake to obtain rivaroxaban intermediate V(4-[4-[(5S)-5-(Aminomethyl)-2-oxo-3-oxazolidinyl]phenyl]-3-morpholinone hydrochloride) 19.66kg,The yield is 90.3%,The purity is 99.78%.

The chemical industry reduces the impact on the environment during synthesis 446292-07-5. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Qilu Pharmaceutical Co., Ltd.; Fan Chuanwen; Leng Chuanxin; Wang Yubing; Liu Peiyuan; (6 pag.)CN109553611; (2019); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

3335-98-6, A common heterocyclic compound, 3335-98-6, name is 1-Phenyloxindole, molecular formula is C14H11NO, 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.

General procedure: A mixture of isatins (1, 1.0 mmol), indolin-2-ones (2, 1.0 mmol) and ZrCl4 (23 mg, 0.1 mmol) was heated in anhydrous ethanol (5 mL) under reflux. After the disappearance of the reactants (8-12 h, monitored by TLC), the mixture was slowly cooled to room temperature. The red solids precipitated and were collected by filtration, then washed by a small amount of anhydrous ethanol to deliver pure compounds 3.

The synthetic route of 3335-98-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Liu, Meilin; Qiu, Shaozhong; Ye, Yu; Yin, Guodong; Tetrahedron Letters; vol. 57; 52; (2016); p. 5856 – 5858;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

3416-57-7, The chemical industry reduces the impact on the environment during synthesis 3416-57-7, name is 2-(2-Oxopropyl)isoindoline-1,3-dione, I believe this compound will play a more active role in future production and life.

A solution of 2-(2-oxopropyl)isoindoline-1,3-dione (101.0 g, 500.0 mmol) in 1,1- dimethoxy-N,N-dimethylmethanamine (400 mL) was heated at 70 C for about 16 h. Cooled to ambient temperature, PE (200 mL) was added, the mixture was stirred at ambient temperature for 1 h. The precipitate was collected by filtration. The solids were placed into a 500 ml round-bottom flask, HOAc (120 mL) was added, the mixture was stirred at ambient temperature for 40 mm and filtrated, the filtrate was concentrated to remove HOAc. The residue was recrystallized from EA (150 mL) to give the product as a yellow solid (18 g, 14.0%). MS (ESI, m/e) [M+1] 258.9.

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

Reference:
Patent; BEIGENE, LTD.; WANG, Zhiwei; GUO, Yunhang; YU, Desheng; (98 pag.)WO2019/34009; (2019); 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. 6326-79-0 name is 6-Bromoisatin, 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. 6326-79-0

Step 1: Into the ice cooled solution of 6-bromoindoline-2,3-dione (0.5 g) in DCM (20 mL), was added neat deoxo-fluor (1.5 g), after 30 min., the reaction was warm to room temperature and stirred for overnight. After being quenched with sodium bicarbonate solution, the reaction mixture was extracted with ethyl acetate and washed with brine. The solvent was removed. the residue was purified by silica gel chromatography to provide 0.48 g of 6-bromo-3,3-difluoroindolin-2-one.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromoisatin, and friends who are interested can also refer to it.

Reference:
Patent; Gilead Scientific Systems, Inc.; Cory, Kevin S; Doo, Jimin; Farrand, Julie; Guerrero, Juan A; Katana, Ashley A; Cato, Daryl; Laisaweed, Scott I; Lee, Jiayao; Lingco, John O; Nicolaus, May; Notte, Gregory; Phyen, Hyeoung-Jung; Sangy, Michael; Sumit, Arun C; Adam J, Surayyah; Stephens, Cork L; Venkatraman, Chandrasekar; Watkins, William J; Yang, Jong Yu; Jabloki, Jeff; Jifel, Shiela; Ro, Jennifer; Lee, Sung H; Jao, Chung Dong; Grove, Jeffery; Su, Jianjun; Blomgren, Peter; Mitchell, Scott A; Shyung, Jin Ming; Chandrasekar, Jayaraman; (460 pag.)KR2016/37198; (2016); A;,
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. 52351-75-4 name is 6-Methoxyindoline-2,3-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. 52351-75-4

A mixture of NaH (11.3 mmol, 2.0 eq) and ylide salt (11.3 mmol, 2.0 eq) was stirred at 0 C for 1h under N2 protection. Then 6-methoxyindoline-2,3-dione (5.6 mmol, 1.0 eq) was added and the mixture was stirred under 80 C for 2h. The resulting solution was poured into satd.aq. NH4Cl, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the product was dissolved in CH3CN, follwed by DMAP (11.3 mmol, 2.0 eq), (Boc)2O (11.3 mmol, 2.0eq) were added, the mixture was stirred under room temperature for 20 min. The crude product product was also obtained after the solvent was removed under reduced pressure and then dissloved in EA and stirred with Pd/C (20% w/w) under H2 condition for 4h under room temperature. The mixture was filtered and purified by silica gel chromatography (petroleum ether/ethyl acetate = 8/1-5/1) to afford the product 1t.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Methoxyindoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Article; Jin, Qiaowen; Zheng, Changwu; Zhao, Gang; Zou, Gang; Tetrahedron; vol. 74; 30; (2018); p. 4134 – 4144;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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

To the suspension of methyl 2-oxoindoline-6-carboxylate (50 gm, 0.261 mol) in IPA (350 ml) was added slowly SMO-powder (33.8 gm, 0.626 mol) and stirred for about 15 min. Benzyl chloride (44 g, 0.313 mol) was added after completion of the reaction at a reaction temperature of -5 to -10C for about 5hrs. The reaction mixture was quenched into ice-water (700 ml) and acidified with Cone. HC1 (2.0-2.5 ml). Filtered the reaction mixture, washed with water (2X100 ml) and dried the precipitate to obtain crude product which can be recrystallized from acetonitrile (28 ml) to obtain methyl-3-(hydroxy(phenyl)methylene)-2- oxoindoline-6-carboxylate pure crystalline solid (32 gm) (61%) (HPLC purity >97%). The filtrate was evaporated in vacuum to give unreacted methyl 2-oxoindoline-6-carboxylate. MR: 216-223C; IR (KBr, cm”1): 3178, 1711, 1651; 1H-NMR (400 MHz, DMSO): delta 3.80 (s, 3H), 7.17 (s, 1H), 7.28-7.31 (m, 2H), 7.46-7.50 (m, 3H), 7.72 (d, 2H, J = 6.0 Hz), 9.52 (s, 1H), 11.53 (s, 1H); 13C-NMR (100 MHz, DMSO): delta 22.12, 52.41, 101.13, 111.13, 119.23, 123.06, 126.65, 127.06, 128.65, 129.21, 132.26, 134.47, 136.99, 166.58, 172.52 and 175.80; MS: m/z 294 [M]”1

The synthetic route of 14192-26-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUVEN LIFE SCIENCES LIMITED; ARAVA, Veera Reddy; GOGIREDDY, Surendra Reddy; JASTI, Venkateswarlu; (45 pag.)WO2016/178064; (2016); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

A common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, molecular formula is C10H9Cl2NO, 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. 118289-55-7.

To a flask equipped with mechanical stirrer, thermometer, condenser and nitrogen inlet was added 6-cUoro-5-(2-cHoroethyl)-l,3-dihydro-2H-indol-2- one (9.0 g, 39.1 mrnol), 3-(l-pirhoerazinyl)-l,2-benzoisothiazole hydrochloride (10.0 g, 39.1 mmol), sodium carbonate (9.96 g, 117.5 mmol) and poly(ethylene glycol) methyl ether (Mn= 350, 40 mL) and the suspension was heated to 120- 1250C under nitrogen for about 48 hrs. The suspension was cooled and poured into water. The suspension was cooled to 20-250C, the product was collected by filtration on a Buchner funnel and the filter cake was rinsed with water at 20-250C. The damp product was transferred to a flask equipped with mechanical stirrer, 100 mL of water were added and the suspension stirred at ambient temperature for 1 h. The suspension was filtered, washed with water and transferred to a drying oven and dried in vacuo. This afforded 14.2 g (88% yield) of crude ziprasidone.

The synthetic route of 6-Chloro-5-(2-chloroethyl)indolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; APOTEX PHARMACHEM INC.; WO2006/47893; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

496-12-8, A common compound: 496-12-8, name is Isoindoline, 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.

A 1.0 g (8.4 mmol) amount of isoindoline was dissolved in 25 mL of acetonitrile. After addition of potassium carbonate (2.3 g ,16.8 mmol), the resulting mixture was heated at 70 C. After 30 min, the solution was allowed to cool to room temperature. A 4.2 mL (47.2 mmol) amount of 1-bromo-3-chloropropane was added and the reaction mixture stirred at room temperature for 24 h. The solvent was removed under reduced pressure and 60 mL water added to the residue. The product was extracted with 3×30 mL dichloromethane. The combined organic fractions were washed with water and dried over sodium sulphate. The solvent was evaporated under reduced pressure. Purification by column chromatography (DCM:MeOH(NH3), 99:1 (v/v)) was performed and enabled collection of the product as a brown liquid (1.27 g,77%). TLC: Rf 0.7 (DCM:MeOH(NH3), 9:1, v/v). 1H NMR (300 MHz,CDCl3) delta: 7.21 (s, 4H, Haro); 3.95 (s, 4H, 2 CH2); 3.69 (t, J 6.8 Hz, 2H,CH2); 2.90 (t, J 7.1 Hz, 2H, CH2); 2.07 (p, J 7.0 Hz, 2H, CH2). 13C NMR (75 MHz, CDCl3) delta: 140.0 (2 Caro); 126.7 (2 Caro); 122.3 (2 Caro); 59.1 (2 CH2); 53.0 (CH2); 43.1 (CH2); 31.9 (CH2). LCMS (ESI+): Calc.for [M+H]: 196.05; 198.07. Found: 195.95; 197.91.

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

Reference:
Article; Donnier-Marechal, Marion; Larchanche, Paul-Emmanuel; Le Broc, Delphine; Furman, Christophe; Carato, Pascal; Melnyk, Patricia; European Journal of Medicinal Chemistry; vol. 89; (2015); p. 198 – 206;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 143262-17-3, name is tert-Butyl 7-bromoindoline-1-carboxylate, 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 143262-17-3, 143262-17-3

tert-butyl 7-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)indoline-l- carboxylate (2): A solution of tert-butyl 7-bromoindoline-l -carboxylate (300 mg, 1.0 mmol) in 1,4-dioxane (6.0 rnL) was treated with bis-pinacolatodiborane (307 mg, 1.2 mmol), potassium acetate (297 mg, 3.0 mmol), and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (41 mg, 0.05 mmol) at 100 ¡ãC for 6 h. After completion of the reaction, the solvent was removed under reduced pressure. The resulting residue was diluted with ethyl acetate and filtered through celite. The filtrate was concentrated under reduced pressure and the residue obtained purified by silica gel column chromatography to afford 2 (260 mg, 75percent) as a pale yellow liquid. MS m/z (M+H): 346.2.

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, tert-Butyl 7-bromoindoline-1-carboxylate, other downstream synthetic routes, hurry up and to see.

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

774-47-0, 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. 774-47-0, name is 5,6-Difluoroindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: Isatins (1a-j, 3.0 g), hydrazine hydrate (80%, 13 mL) and water (13 mL) were added to a flask equipped with a thermometer with vigorous stirring. The reaction mixture was kept at 140 C in an oil bath for 6 h before being cooled to r.t., when hydrochloric acid (2.0 mol L-1) was added to bring the pH to pH 2. The reaction mixture was stirred at r.t. for 12 h. Compounds 2a-j were obtained by filtering under vacuum and recrystallisation from absolute ethanol.

The synthetic route of 5,6-Difluoroindoline-2,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Chao; Xu, Juan; Zhao, Xinyu; Kang, Congmin; Journal of Chemical Research; vol. 41; 9; (2017); p. 537 – 540;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem