Month: March 2021

Electric Literature of 346-34-9, A common heterocyclic compound, 346-34-9, name is 4-Fluoroindoline-2,3-dione, molecular formula is C8H4FNO2, 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.

Intermediate 1 A6-bromo-2-(trifluoromethyl)quinoline-4-carboxylic acid 300 mg (1.33 mmol) of 5-bromo-1 H-indole-2,3-dione was suspended in 3 mL water in a microwave vial. 82 mg ( 1.46 mmol) potassium hydroxide, 152 muL (2.65 mmol) acetic acid and 152 mg (1.86 mmol) sodium acetate were added so that the pH was around 5. The solution was cooled to 10 C and 238 muL (2.65 mmol) 1 ,1,1 -trifluoroacetone was added rapidly, the microwave vial was sealed and heated in the microwave for 2 h at 120 C. The reaction was stopped by the addition of 10% aqueous hydrochloric acid solution and the resulting precipitate was isolated by filtration, washed with water and dried in a vacuum drying cabinet at 50 C overnight to obtain 409 mg (1.28 mmol, 96%) of the desired title compound .1 H NMR (300 MHz, DMSO d6): delta (ppm) = 8.14 (dd, 1 H), 8.21 (d, 1 H), 8.32 (s, 1 H), 9.09 (d, 1 H), 14.50 (br. s. , 1 H)._In analogy to intermediate l, 300 mg (1.81 mmol) 4-fluoro-1H-indole-2,3-dione washeated with 326 pL (3.63 mmoL) 1,1,1-trifluoroacetone, 112 mg (1.99 mmoL)potassium hydroxide, 208 pL (3.63 mmo[) acetic acid and 209 mg (2.54 mmoL) sodium acetate in 3 mL water for 2 h at 100CC in the microwave to obtain 315 mg (1.22 mmol, 67%) of the desired title compound after aqueous work-up.1H NMR (400MHz, DMSO d6): 6 (ppm) = 783 -7.92 (m, 1 H), 8.09 (dd, 1 H), 8.25 (s, 1 H), 8.90 (dd, 1 H), 14.50 (br. 5., 1 H).

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:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; HEISLER, Iring; MUeLLER, Thomas; SIEBENEICHER, Holger; BUCHMANN, Bernd; CLEVE, Arwed; GUeNTHER, Judith; KOPPITZ, Marcus; HEROULT, Melanie; NEUHAUS, Roland; PETRUL, Heike; QUANZ-SCHOeFFEL, Maria; WO2015/91428; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 4403-36-5, name is 2-(1,3-Dioxoisoindolin-2-yl)ethanesulfonylchloride, 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 4403-36-5, Computed Properties of C10H8ClNO4S

Example 42 N-({(2R,3S)-3-[(4-azepan-1-ylpyrimidin-2-yl)amino]-1-cyclohexylpyrrolidin-2-yl }methyl)-2-(1,3 -dioxo-1,3-dihydro-2H-isoindol-2-yl)ethanesulfonamide (compound 42) N-[(2R,3S)-2-(aminomethyl)-1-cyclohexylpyrrolidin-3-yl]-4-azepan-1-ylpyrimidine-2-amine (33.2 mg) was dissolved in anhydrous tetrahydrofuran (0.8 mL) and dimethylformamide (0.4 mL) under an argon atmosphere at room temperature, trietylamine (24.8 muL) and 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethanesulfonyl chloride (48.8 mg) were added into the solution and the solution was stirred at room temperature for overnight. The reaction solution was added aqueous saturated sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and then concentrated. The residue was purified by Flash tube (trade mark) to obtain sulfonamide compound (49.0 mg). TLC: Rf 0.67 (chloroform: methanol = 5:1).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(1,3-Dioxoisoindolin-2-yl)ethanesulfonylchloride, and friends who are interested can also refer to it.

Reference:
Patent; ONO PHARMACEUTICAL CO., LTD.; EP1852432; (2007); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 87-48-9, 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 87-48-9 as follows.

In a 5L four-necked flask, add 5-bromoisatin 250.0g,1000ml absolute ethanol, stirring, and then slowly add hydrationHydrazine (80%) 81.4g, heated to reflux (80 C)Reaction 2h,Sampling HPLC test, no raw material remaining, the reaction liquid coolingTo about 15 , crystallization 15min, filtered, the filter cake was washed with a small amount of cold ethanol or mother liquor,Then at 50 oven drying 12h, get hydrazone crude. In a 5L four-necked flask, put the crude hydrazide obtained above,Ethylene glycol 1000ml, stirring, adding sodium hydroxide 32.5g,Heated to reflux,Reflux temperature gradually increased from 95 to 115 , the reaction 7h,Sample HPLC test, no raw material remaining, stop heating, cooling to below 30 , the reaction solution was transferred to a 10L bottle, add water 1500ml, with concentrated hydrochloric acid to adjust PH = 2.5 or so, adding methylene chloride 1500ml, The floc was precipitated, filtered, and the layers were separated. The aqueous layer was further extracted with 500 ml of dichloromethane, and the organic layers were combined.The solvent was distilled off under reduced pressure to give 402.4 g of bromoindolinone (Formula II).

According to the analysis of related databases, 87-48-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ningbo Jiu Sheng Chuangxin Pharmaceutical Technology Co., Ltd.; Li Changlong; Yu Lihuang; He Guojin; Tao Weijian; (7 pag.)CN104693019; (2017); B;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 56341-37-8, name is 6-Chlorooxindole belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. name: 6-Chlorooxindole

EXAMPLE 9b; Preparation of intermediate E/Z-2-[4-bromo-2-(6-chloro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-phenoxy]-2-methyl-propionic acid ethyl ester; To the mixture of 6-chlorooxindole (10.6 g, 63 mmol) and 2-(4-bromo-2-formyl-phenoxy)-2-methyl-propionic acid ethyl ester (20 g, 63 mmol) in methanol (150 mL) was added pyrrolidine (4.5 g, 6 3 mmol) dropwise. The mixture was then heated at 70 C. for 1 h. After cooled to 4 C., the mixture was filtered and the precipitate was collected, dried to give a mixture of E/Z-2-[4-bromo-2-(6-chloro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-phenoxy]-2-methyl-propionic acid ethyl ester (18.5 g, 63%).

The synthetic route of 56341-37-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chen, Li; Han, Xingchun; He, Yun; Yang, Song; Zhang, Zhuming; US2009/163512; (2009); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 959235-95-1,Some common heterocyclic compound, 959235-95-1, name is 6-(Trifluoromethoxy)indoline, molecular formula is C9H8F3NO, 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 a stirring solution of 2-(4-chloro-2-(4-methoxy-3,3-dimethyl-4- oxobutoxy)phenyl)acetic acid 14b (576 mg, 1 .83 mmol), 6- (trifluoromethoxy)indoline [CAS 959235-95-1 ] (409 mg, 2.01 mmol) anddiisopropylethylamine (907 muIota_, 5.49 mmol) in DMF (7.5 ml_) under N2-atm was added HATU (1 .07 g, 2.75 mmol), and the reaction mixture was stirred at room temperature for 5 h. Water (30 ml_) was added, and the product was extracted (2x) with Et2O. The combined organic layers were washed with brine, dried overMgSO4, filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (40 g) using a gradient of heptane/EtOAc 100/0 to 0/100. The desired fractions were combined and evaporated under reduced pressure, and co-evaporated with toluene. The residue was dried under vacuum at 45C to provide methyl 4-(5-chloro-2-(2-oxo-2-(6- (trifluoromethoxy)indolin-1 -yl)ethyl)phenoxy)-2,2-dimethylbutanoate 14c (790 mg) as a powder.

The synthetic route of 959235-95-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICALS, INC.; KATHOLIEKE UNIVERSITEIT LEUVEN; KESTELEYN, Bart Rudolf Romanie; BONFANTI, Jean-Francois; COESEMANS, Erwin; RABOISSON, Pierre Jean-Marie Bernard; MARCHAND, Arnaud Didier M; BARDIOT, Dorothee Alice Marie-Eve; (92 pag.)WO2018/178240; (2018); A1;,
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. 3484-35-3, name is 5-Methylindolin-2-one, A new synthetic method of this compound is introduced below., SDS of cas: 3484-35-3

General procedure: Equimolar quantity of 5-substituted-1H-indolin-2-ones and 2-(4-formylphenoxy)-N-substituted-phenyl-acetamide was taken into round bottom flask containing 50 mL of methanol, followed by 2-3 drops of piperidine. The reaction mixture was refluxed for 1-4 h or till the end of reaction as confirmed by TLC. Then, it was cooled to room temperature and, the solution was filtered. The obtained residue was recrystallized by using dimethylformamide and ethanol.

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; Bhadauria, Vivek Singh; Sravanthi, Vishnu; Kumar, Sujeet; Das, Debajyoti; De Clercq, Erik; Schols, Dominique; Tokuda, Harukuni; Karki, Subhas S.; Acta poloniae pharmaceutica; vol. 74; 1; (2017); p. 137 – 145;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 2913-97-5, name is N-(2-Oxoethyl)phthalimide, 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. category: indolines-derivatives

EXAMPLE 3F tert-butyl(2S,3S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3-methylpentanoate A solution of the product of Example 3E (36.81 g) in methanol (50 mL) was treated with L-iso-leucine tert-butyl ester hydrochloride (30 g, 134 mmol), sodium cyanoborohydride (16.9 g, 268 mmol), and acetic acid (4.6 ml, 80.4 mmol), stirred at 25¡ã C. for 3 hours and concentrated. The concentrate was partitioned between dichloromethane and saturated NaHCO3. The organic phase was washed with brine and dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel, eluding with a gradient starting with 10percent-66percent ethyl acetate in hexanes to give the title compound (28.44 g, 59percent yield).

The synthetic route of N-(2-Oxoethyl)phthalimide has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DeGoey, David A.; Flentge, Charles A.; Flosi, William J.; Grampovnik, David J.; Kempf, Dale J.; Klein, Larry L.; Yeung, Ming C.; Randolph, John T.; Wang, Xiu C.; Yu, Su; US2005/148623; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 104618-31-7, name is 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione, 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 104618-31-7, Quality Control of 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione

Step 2 A solution of 2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (3.10 g, 12.6 mmol) in CH2Cl2 (25.0 mL) was added to a slurry of PCC (4.10 g, 19.0 mmol) in CH2Cl2 (15.0 mL) and stirred at room temperature for 3.5 hours. The reaction was diluted with Et2O (60.0 mL), decanted and the residue swirled with Et2O (2*40.0 mL). The combined ether layers were filtered through florisil and concentrated in vacuo to dryness, and the residue was recrystallized from ethyl acetate/hexane to give 2.01 g (65%) of 2-(4-oxocyclohexyl)-1H-isoindole-1,3(2H)-dione as colorless needles: mp 140.3-142.1 C.; 1H NMR (400 MHz, CDCl3) delta7.84, 7.74, 4.64, 2.72, 2.54, 2.09; 13C NMR (100 MHz, CDCl3) delta208.9, 168.1, 134.1, 131.9, 123.3, 48.4, 39.9, 28.6; IR (mull) 3062, 3031, 2958, 2949, 2919, 2885, 1775, 1762, 1721, 1708, 1611, 1465, 1436, 1419, 1393, 1379, 719 cm-1; HRMS (FAB) calcd for C14H14NO3: 244.0974, found 244.0976; Anal. Calcd for C-14H14NO3: C, 69.12; H, 5.39; N, 5.76. Found: C, 68.87; H, 5.47; N, 5.73.

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, 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Fu, Jian-Min; US2003/100596; (2003); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 169037-23-4, 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. 169037-23-4 name is 5-(Trifluoromethoxy)indoline-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.

General procedure: A mixture of beta-nitrostyrenes, isatin and tyrosine (1:1:1) was stirredunder heating at 100 C for 1 h in [bmim]Br (200 mg). After the reaction was completed, 10 mL of ethyl acetate was added to the reaction mixture and stirred for 15 min. The organic layer was separated, washed with water, and dried. The cycloadduct was further purified using hexane: ethyl acetate (3:2 v/v) as eluent employing column chromatography technique. After extraction of the cycloadduct, [bmim]Br wasdried under vacuum at 80 C for 2 h to exclude any water trapped from moisture and reused for subsequent runs.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-(Trifluoromethoxy)indoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Article; Kumar, Raju Suresh; Almansour, Abdulrahman I.; Arumugam, Natarajan; Mohammad, Faruq; Kotresha; Menendez, J. Carlos; Bioorganic and Medicinal Chemistry; vol. 27; 12; (2019); p. 2487 – 2498;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 20870-79-5, name is 5-Nitroindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Computed Properties of C8H6N2O3

5-Amino-2-oxindole 5-Nitro-2-oxindole (6.3 g) was hydrogenated in methanol over 10% palladium on carbon to give 3.0 g (60% yield) of the title compound as a white solid.

The synthetic route of 20870-79-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUGEN, Inc.; US2003/69421; (2003); A1;; ; Patent; Pharmacia Corporation; US2003/216410; (2003); A1;; ; Patent; Sugen, Inc.; US6051593; (2000); A;; ; Patent; Tang, Peng Cho; Miller, Todd A.; Li, Xiaoyuan; Sun, Li; Wei, Chung Chen; Shirazian, Shahrzad; Liang, Congxin; Vojkovsky, Tomas; Nematalla, Asaad S.; Hawley, Michael; US2002/156292; (2002); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem