Month: September 2021

Application of 104618-31-7, These common heterocyclic compound, 104618-31-7, name is 2-(4-Hydroxycyclohexyl)isoindoline-1,3-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.

To a mixture of 7-bromoquinoxalin-5-ol (47.53 g, 211.2 mmol), 2-(4- hydroxycyclohexyl)isoindoline-l,3-dione (52.41 g, 213.7 mmol), and PPh3 (87.31 g, 332.9 mmol) in THF (740 mL) at 21 C was added tert-butyl (NZ)-N-tert- butoxycarbonyliminocarbamate (DTBAD) (79.51 g, 328.0 mmol) in portions over 40 min so as to maintain the temperature below 30 C and the resultant reaction mixture was stirred at room temperature for a further 20 h. The reaction was evaporated in vacuo. The residual reddish-brown viscous oil was dissolved in CH2C12 and filtered through a plug of silica in a glass column using applied air pressure (plug was made with 1L of dry silica suspended in CH2C12). The plug was eluted with CH2C12, the fractions were combined and evaporated in vacuo to afford a red-brown viscous oil/foam, that was then dissolved in 700 mL of MeOH before precipitating. The mixture was stirred at room temperature for 1 h, filtered, washed with cold MeOH (500 mL) and Et20 (100 mL), then dried in vacuo to yield a tan solid that was suspended in 300 mL MeOH and brought to reflux for 10 min. The suspension was cooled to room temperature and filtered, washed with a further MeOH and Et20 (4: 1), and dried in vacuo to provide 2-[4-(7- bromoquinoxalin-5-yl)oxycyclohexyl]isoindoline-l,3-dione (58.43 g, 126.6 mmol, 59.94%). 1H NMR (400 MHz, CDC13) d 8.96 (d, J = 1.8 Hz, 1H), 8.86 (d, J = 1.8 Hz, 1H), 7.91 (d, J = 1.9 Hz, 1H), 7.89 – 7.82 (m, 2H), 7.78 – 7.67 (m, 2H), 7.30 (d, J = 1.9 Hz, 1H), 4.95 (s, 1H), 4.29 (tt, J = 12.5, 3.7 Hz, 1H), 2.87 (qd, J = 13.1, 3.5 Hz, 2H), 2.44 (d, J = 15.2 Hz, 2H), 1.80 (t, J = 14.1 Hz, 2H), 1.67 (d, 2H). ESI-MS m/z calc. 451.05316, found 452.19 (M+l)+; Retention time: 0.92 minutes.

Statistics shows that 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione is playing an increasingly important role. we look forward to future research findings about 104618-31-7.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WEINBERG, Marc, Saul; D’ASTOLFO, Diego, Sebastian; MAHAJAN, Sudipta; (258 pag.)WO2019/143675; (2019); 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, Recommanded Product: 104618-31-7

To a solution of PPh3 (1.28 g, 4.9 mmol) in THF (12 mL) was added dropwise DEAD (852 mg, 4.9 mmol) at -10 C. After the white solid was appeared, compound 2-(4-hydroxycyclohexyl)isoindoline-1,3-dione (600 mg, 2.45 mmol) was added, followed by CH3COSH (0.35 mL, 4.9 mmol) at -10 C. The mixture was stirred at room temperature overnight. TLC (PE:EA=1:1) showed the reaction was complete. The mixture was poured into water (200 mL) and extracted with EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL×3). The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo to give S-(4-(1,3-dioxoisoindolin-2-yl)cyclohexyl) ethanethioate (600 mg, 81%) as a white solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; Tolero Pharmaceuticals, Inc.; Xu, Yong; Brenning, Benjamin Gary; Kultgen, Steven G.; Liu, Xiaohui; Saunders, Michael; Ho, Koc-Kan; (119 pag.)US9416132; (2016); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 87-48-9, 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. 87-48-9, name is 5-Bromoindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: Isatins I (3.0 mmol) was dissolved in anhydrous DMF (15 mL), and the resultant solution was cooled to 0 C (ice bath), whereupon sodium hydride (60% dispersion in mineral oil, 140mg, 3.5 mmol, 1.17 equiv) was added in one portion and stirred for 5 minutes. Iodomethane (497 mg, 3.5 mmol, 1.17 equiv) or benzyl bromide (564.3 mg, 3.3 mmol, 1.1 equiv) was added and the reaction was stirred at 0 C for 30min. The reaction was monitored by TLC until I was fully consumed. The reaction mixture was then poured into saturated aqueous NH4Cl and extracted with ethyl acetate. The combined organic portions were washed with water and brine, dried (MgSO4), filtered, and concentrated to give N-methyl isatins and N-benzyl isatins II (90%-100% yield).

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

Reference:
Article; Liang, Jin-Yan; Wang, Hui; Yang, Yan-Li; Shen, Shou-Jie; Chen, Jian-Xin; Tetrahedron Letters; vol. 58; 27; (2017); p. 2636 – 2639;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 611-09-6, name is 5-Nitroindoline-2,3-dione, This compound has unique chemical properties. The synthetic route is as follows., name: 5-Nitroindoline-2,3-dione

General procedure: A mixture of dimedone (0.140 g, 1 mmol), isatin (0.147 g, 1 mmol) and malononitrile (0.066 g, 1 mmol) was stirred in round bottom flask containing 5 mL of oxalic acid dihydrate:proline LTTM at room temperature for an appropriate time. After completion of the reaction, as indicated by TLC, 10 mL of water was added to the reaction mixture and the insoluble crude product was filtered off. The aqueous layer was evaporatedunder vacuumto recover the LTTM. The crude product was washed with distilled water(5 mL) and recrystallized from ethanol (10 mL).

According to the analysis of related databases, 611-09-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Chandam, Dattatray R.; Mulik, Abhijeet G.; Patil, Dayanand R.; Deshmukh, Madhukar B.; Research on Chemical Intermediates; vol. 42; 2; (2016); p. 1411 – 1423;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 114041-16-6, 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. 114041-16-6, name is 5,6-Dimethoxyisoindoline belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Compound 8 (70.6 mg, 0.24 mmol) and 5,6-dimethoxyisoindoline(68.5 mg, 0.38 mmol) were dissolved in CH3CN (30 mL), followed by addition of K2CO3 (138.8 mg, 1.00 mmol). The mixture was heated under reflux and stirred at 90 C for 6 h. After cooling and filtration, the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography (petroleum ether/ethyl acetate/triethyamine) = 10:10:1, v/v/v) to afford 13(56.8 mg, 59%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): d7.15-7.06 (m, 3H, Ar-H), 6.77 (s, 2H, Ar-H), 6.66 (dd, J = 3.1,0.5 Hz, 1H, Ar-H), 6.52 (d, J = 7.2 Hz, 1H, Ar-H), 4.84 (dt, J = 47.5,4.2 Hz, 2H, F-CH2), 4.37 (dt, J = 27.8, 4.3 Hz, 2H, O-CH2), 4.27 (t,J = 6.7 Hz, 2H, indole N-CH2), 3.87 (s, 10H, O-CH3, Ar-CH2-N), 2.65(t, J = 6.7 Hz, 2H, N-CH2), 2.08-2.05 (m, 2H, CH2). 13C NMR(100 MHz, CDCl3) d (ppm): 152.43, 148.63, 137.94, 131.86,127.08, 122.29, 119.61, 106.14, 103.84, 100.64, 98.63, 82.35(J = 169.2, F-CH2), 67.49 (J = 20.6, O-CH2), 59.32, 56.34, 52.75,44.12, 29.56. ESI-TOF MS calcd for C23H28FN2O3 [M+H]+:399.2084; found: 399.2076.

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

Reference:
Article; Wang, Liang; Ye, Jiajun; He, Yingfang; Deuther-Conrad, Winnie; Zhang, Jinming; Zhang, Xiaojun; Cui, Mengchao; Steinbach, Joerg; Huang, Yiyun; Brust, Peter; Jia, Hongmei; Bioorganic and Medicinal Chemistry; vol. 25; 14; (2017); p. 3792 – 3802;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 17564-64-6, These common heterocyclic compound, 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-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.

General procedure: The initial carbonyl compound (50 mmol) was dissolved/suspended in ethanol (50 mL) and magnetically stirred with thiosemicarbazide (50 mmol) and catalytic amounts of acetic acid for 8-24 h at room temperature. The obtained thiosemicarbazone was filtered, washed with appropriate solvent (n-hexane, petroleumether or diethyl ether) and dried under vacuum. The intermediate thiosemicarbazone (50 mmol) reacted with ethyl bromoacetate (50 mmol), in methanol (50 mL) and sodium acetate (50 mmol) at room temperature under magnetic stirring for 24 h. The resulting 4-thiazolidinone was poured on ice, filtered or extracted with chloroform (3 x 100 mL) and purified by column chromatography (SiO2, ethyl acetate/n-hexane). Then, the obtained thiazolidinone (50 mmol) was dissolved/suspended in 50 mL of anhydrous acetone in the presence of anhydrous potassium carbonate (50 mmol), and reacted with equimolar amounts of 4-nitrobenzyl bromide, 1-(chloromethyl)naphthalene and N-(chloromethyl)phthalimide for 24-48 h. The product was poured on ice, filtered or extracted with chloroform (3 x 50 mL) and purified by column chromatography (SiO2, ethyl acetate/n-hexane) in order to obtain the title compoundsin high yields. 7.1.53 2-((2-(2-(Propan-2-ylidene)hydrazono)-4-oxothiazolidin-3-yl)methyl)isoindoline-1,3-dione (1C) Yellow powder, mp 119-124 C, 99% yield; 1H NMR (400 MHz, DMSO-d6): delta 1.79 (s, 3H, CH3), 1.88 (s, 3H, CH3), 3.95 (s, 2H, CH2, thiazolidinone), 5.52 (s, 2H, ArCH2), 7.73-8.31 (m, 4H, Ar).

Statistics shows that 2-(Chloromethyl)isoindoline-1,3-dione is playing an increasingly important role. we look forward to future research findings about 17564-64-6.

Reference:
Article; De Monte, Celeste; Carradori, Simone; Bizzarri, Bruna; Bolasco, Adriana; Caprara, Federica; Mollica, Adriano; Rivanera, Daniela; Mari, Emanuela; Zicari, Alessandra; Akdemir, Atilla; Secci, Daniela; European Journal of Medicinal Chemistry; vol. 107; (2016); p. 82 – 96;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 147149-84-6, A common heterocyclic compound, 147149-84-6, name is 4-Bromo-5-methylindoline-2,3-dione, molecular formula is C9H6BrNO2, 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.

Hydrogen peroxide (40 ml, 391.60 mmol) was added to a solution of 4-bromo-5-methyl-1H-indole-2,3-dione (20 g, 83.31 mmol) in 2M NaOH (400 ml) at rt. The resulting solution was stirred at rt for 2 h. Sodium sulfite (48 g) was then added and the mixture was stirred for another 0.5 h at rt. The reaction mixture was extracted with EtOAc (200 mL) and the aqueous layer pH adjusted to pH 4 with concentrated HCl. A precipitate was collected by filtration, washed with water (300 ml) and dried under vacuum to afford 6-amino-2-bromo-3-methylbenzoic acid (12.4 g, 65%) as a pale yellow solid; 1H NMR (400 MHz, MeOD, 30 C.) 2.29 (3H, s), 6.70 (1H, d), 7.07 (1H, d); m/z: ES+ [M+H]+=230.

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; ASTRAZENECA AB; Kettle, Jason Grant; Bagal, Sharanjeet; Robb, Graeme Richard; Smith, James Michael; Goldberg, Frederick Woolf; Cassar, Doyle Joseph; Feron, James Lyman; US2019/177338; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 39603-24-2,Some common heterocyclic compound, 39603-24-2, name is 5,7-Dimethylindoline-2,3-dione, molecular formula is C10H9NO2, 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.

j0309j A. 6,8-Dimethyl-2-(3-methyl-1-benzofuran-2-yl)quinoline-4-carboxylic acid. To a100 ml. round-bottom flask was placed a solution of 1-(3-methyl-1-benzofuran-2-yl)ethan-1-one (1 g,5.74 mmol) in EtOH (20 mL) then 5,7-dimethyl-2,3-d1H ydro-1H -indole-2,3-dione(800 mg,4.57 mmol) and KOH (800 mg) were added. The resulting solution was heated to80C and stirred for 16 h. The reaction was cooled to rt and concentrated under reducedpressure. The residue was dissolved in 100 mL of H20,washed with MTBE (3×50 mL),and the pH of the solution was adjusted to 2-3 with 2N HC1. The resulting precipitate was isolated by filtration and washed with MeOH (3×50 mL) affording 485 mg (32%) of the title compound as a yellow solid. Mass Spectrum (LCMS,ESI pos): Calcd. for C2,H,8NO3: 332.1 (M+H); Found: 332.0. 1H NMR (300 MHz,DMSO-d6): oe 13.95 (s,1H ),8.43 (s,1H ),8.33 (s,1H ),7.80-7.77 (d,J= 7.5 Hz,1H ),7.73-7.70 (d,J= 8.1H z,1H ),7.61 (s,1H ),7.47-7.42 (t,J= 7.5 Hz,1H ),7.38-7.33 (t,J= 7.5 Hz,1H ),2.85 (s,3H),2.73 (s,3H),2.52 (s,3H). HPLC purity(254 nm): 99.5%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5,7-Dimethylindoline-2,3-dione, its application will become more common.

Reference:
Patent; PROTEOSTASIS THERAPEUTICS, INC.; MUNOZ, Benito; BASTOS, Cecilia, M.; PARKS, Daniel; KOMBO, David; (301 pag.)WO2017/62581; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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 5332-26-3 as follows. Recommanded Product: 5332-26-3

Methyl 3-(1 ,3-dioxoisoindolin-2-yl)-2-(4-(triisopropylsilyloxy)phenyl) propanoate (E3) was prepared from E2 according to the below:To a solution of LiHMDS in THF cooled to -78C was added a cooled solution (approx – 78C) of methyl-2-(4-(triisopropylsilyloxy) phenyl)acetate (E2) in THF via syringe. The solution was stirred at -78C for 30 min. Bromo-methyl phthalimide was added directly to the anion, and the solution was immediately removed from the -78C bath and placed in an ice bath and stirred for 2 h. The reaction was then poured into NH4CI(sat) and extracted with EtOAc. The organics were dried (Na2SO4), filtered, and evaporated. Column chromatography 0-20% EtOAc/Hexanes gave pure methyl 3-(1 ,3-dioxoisoindolin-2-yl)-2-(4- (triisopropylsilyloxy)phenyl)propanoate (E3).

According to the analysis of related databases, 5332-26-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AERIE PHARMACEUTICALS, INC.; DELONG, Mitchell, A.; STURDIVANT, Jill, Marie; ROYALTY, Susan, M.; HEINTZELMAN, Geoffrey, Richard; YINGLING, Jeffrey, D.; KOPCZYNSKI, Casey; WO2010/127329; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 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.

EXAMPLE I 5-acetyl-2-indolinone 171 g (1.28 mol) aluminium chloride in 500 ml 1,2-dichloroethane are cooled in the ice bath. Then 78 g (1.1 mol) acetylchloride are added dropwise, so that the temperature does not exceed 10 C. After 1 h, 71.3 g (0.53 mol) 2-indolinone (1,3-dihydro-indol-2-one) are added in 4 batches and the temperature is kept at 10-12 C. The reaction mixture is left overnight to warm up slowly to ambient temperature. Then the solution is slowly added to 1 kg ice with vigorous stirring. The slurry is diluted with 1 l water and stirred for another 30 min. Then the precipitate is suction filtered. Yield: 80.9 g (86.3% of theory) Rf=0.36 (silica gel, ethyl acetate/cyclohexane/methanol 9:9:2) C10HgNO2 (MG=175.19) Mass spectrum: m/z=174 (M-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; Boehringer Ingelheim International GmbH; US2005/234120; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem