Category: indolines-derivatives

Application of 3783-77-5, A common heterocyclic compound, 3783-77-5, name is 2-(3-Oxobutyl)isoindoline-1,3-dione, molecular formula is C12H11NO3, 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 mixture of 50 g of 2- (3-oxobutyl) isoindoline-1,3-dione, 14.3 g of ethylene glycol and 7.4 g of p-toluenesulfonium tetrahydrate were dissolved in 500 ml of anhydrous toluene and treated with a water separator Reflux for 24 hours. After completion of the reaction, the reaction system was saturatedNaHCO3 aqueous solution 500 ml twice. The aqueous phase was extracted twice with 500 ml of ethyl acetate. The organic phase is combined with anhydrous sulfur Dried over sodium carbonate, and the solvent was distilled off under reduced pressure to obtain a distillation residue which was recrystallized from ethanol to give 45 g of a yellow solid: 2- (2-(2-methyl-1,3-dioxolan-2-yl) ethyl) isoindoline-1,3-dione, yield: 74.8%.

The synthetic route of 3783-77-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Wuhan Yao Ming Kant, Immanuel New Drug Development Co., Ltd.; Yu Lingbo; Wang Ruile; Zhou Qiang; Xu Xueqin; Zhang Dawei; Bai Youyin; Chen Dongzhi; Gao Mingfei; Yao Baoyuan; Han Huaxin; Fu Xinyu; Ma Rujian; (5 pag.)CN106939001; (2017); A;,
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Synthetic Route of 423116-18-1, A common heterocyclic compound, 423116-18-1, name is 2-(4-Oxocyclohexylmethyl)isoindole-1,3-dione, molecular formula is C15H15NO3, 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.

Sodium cyanoborohydride (48.5 g, 772 mmol) was added portionwise to a solution of 2-((4-oxocyclohexyl)methyl)isoindoline-1,3-dione (100 g, 389 mmol, Intermediate 34) in AcOH (1.0 L), and the resulting mixture was stirred at rt for 16 h. After this time, the mixture was concentrated, and the concentrate was dissolved in EtOAc. The resulting solution washed twice with a saturated aqueous NaHCO3 solution, dried with anhydrous Na2SO4, filtered, and concentrated to afford the title compound as a colorless solid, which was used in the next step without further purification.

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; Janssen Pharmaceutica NV; Goldberg, Steven; Martin, Connor L.; Fennema, Elizabeth G.; Wolin, Ronald L.; Fourie, Anne M.; Xue, Xiaohua; (85 pag.)US2019/382350; (2019); 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 17702-83-9 as follows. Application In Synthesis of 2-(8-Bromooctyl)isoindoline-1,3-dione

step 1 8-(Benzoxazol-2-ylsulfanyl)-octylamine To a round bottom flask with 2-mercaptobenzoxazole (2.14 g, 14.2 mmol) andDMF (100 mL) at room temperature was added K2CO3 (2.61 g, 18.9 mmol) followed by N-(8-bromooctyl)phthalimide (4.00 g, 11.8 mmol). The resulting solution was heated to 60° C. for 0.5 h and then cooled back to room temperature. At this point, the reaction mixture was quenched with H2O (100 mL) and then diluted with EtOAc (600 mL). The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20percent EtOAc/petroleum ether gradient) to afford the thioether intermediate. To this thioether intermediate (3.02 g, 7.39 mmol) in MeOH (40 mL) at room temperature was added hydrazine monohydrate (0.860 mL, 17.7 mmol) and the resulting mixture was heated to reflux. After 18 h at this temperature, the reaction was concentrated, taken up in EtOAc (300 mL), and filtered to remove insoluble materials. This phthalimide byproduct was washed with excess EtAOc, and the filtrate was washed with H2O (40 mL) and brine (40 mL). The organic layer was then dried (Na2SO4) and concentrated to afford the product (1.87 g, 57percent) as an oil; 1H NMR (CDCl3) delta1.14-1.67 (m, 12H), 1.72-1.92 (m, 2H), 2.69 (t, J=9.6 Hz, 2H), 3.32 (t, J=8.5 Hz, 2H), 7.16-7.34 (m, 2H), 7.38-7.47 (m, 1H), 7.54-7.66 (m, 1H); mass spectrum [(+) ESI], m/z 279(M+H)+.

According to the analysis of related databases, 17702-83-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Butera, John A.; Caufield, Craig E.; Graceffa, Russell F.; Greenfield, Alexander; Gundersen, Eric G.; Havran, Lisa Marie; Katz, Alan H.; Lennox, Joseph R.; Mayer, Scott C.; McDevitt, Robert E.; US6214877; (2001); B1;,
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. 3335-98-6, name is 1-Phenyloxindole, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C14H11NO

General procedure: A mixture of oxindoles (2.0102 mmol), cinnamaldehyde,a base and a prescribed amount of TIPS-b-CDwas stirred in solvents(2 mL) at 10 C. After the removal of solvent in vacuo, the residuewas analyzed by 1H NMR to determine the reaction conversion andproduct distributions. The product was isolated by silica gel columnchromatography with a hexane/ethyl acetate (4:1, v/v) eluent. 4.5.12 (E)-N-Phenyl-3-(3′-phenylallylidene)-indolin-2-one ((E)-3g) Yellow prisms: mp 158-159 C, 1H NMR (DMSO-d6) delta 6.79 (d, J=7.7 Hz, 1H), 7.16 (dd, J=7.7, 7.7 Hz, 1H), 7.28 (dd, J=7.7, 7.7 Hz, 1H), 7.40-7.50 (m, 7H), 7.51 (s, 1H), 7.56-7.61 (m, 2H), 7.82-7.89 (m, 3H), 8.17 (d, J=7.7 Hz, 1H). 13C NMR (DMSO-d6) delta 109.0, 121.5, 122.7, 123.2, 124.2, 124.4, 126.9, 127.9, 128.3, 129.0, 129.2, 129.6, 130.0, 134.4, 135.8, 136.2, 142.8, 145.8, 166.9. IR: 1699.82 (C=O). HRMS (EI) m/z calcd for C23H17NO: 323.1310, found 323.1313.

According to the analysis of related databases, 3335-98-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Asahara, Haruyasu; Kida, Toshiyuki; Hinoue, Tomoaki; Akashi, Mitsuru; Tetrahedron; vol. 69; 45; (2013); p. 9428 – 9433;,
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. 1914-02-9, name is 3,3-Dimethylindoline, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 3,3-Dimethylindoline

Sodium bicarbonate (5.41 g, 64.39 mmol) and3,3-dimethylindoline (0.79 g, 5.37 mmol)Was suspended in dichloromethane (10 mL)The mixture was cooled to 0 C,Acetyl chloride (0.76 mL, 10.73 mmol) was added dropwise thereto.The reaction solution was stirred at room temperature for 2 hours and then filtered. The filtrate was concentrated under reduced pressure,The title compound was obtained as a white solid (0.99 g, 97.1%).

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 1914-02-9.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; Wang Ruyong; Wang Liang; (112 pag.)CN104016979; (2017); B;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 6341-92-0,Some common heterocyclic compound, 6341-92-0, name is 6-Chloroisatin, molecular formula is C8H4ClNO2, 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 isatin 1 (1.0 mmol), malononitrile or cyanoacetic ester 2 (1.0 mmol), phthalhydrazide (1.0 mmol), and NiCl2 (0.2 mmol) in PEG 600 (5 mL) was stirred at 100 C for the appropriate time (refPreviewPlaceHolderTable 2). After complete conversion as indicated by TLC, water was added and the product was extracted with ethyl acetate (2×10 ml). The organic phase was dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was recrystallized from ethanol to afford the pure product.

The synthetic route of 6341-92-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Xiao-Nan; Li, Yong-Xiao; Zhang, Zhan-Hui; Tetrahedron; vol. 67; 38; (2011); p. 7426 – 7430;,
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 60434-13-1 as follows. HPLC of Formula: C9H6ClNO2

General procedure: To a mixture of isatin (1 equiv.) and phenyl acetylene (1.2 equiv.) in water (3 mL), CuWO4 (10 mol%) and DABCO (40 mol%) were added at room temperature and the mixture was heated at 60 C for 2 to 5 h. After completion of reaction (monitoring by TLC) mixture was cooled to room temperature and extracted with EtOAc (2×10 mL). The organic layers were washed with brine, dried using sodium sulfate. Evaporation of the solvent gave the crude product which was purified by silica gel column chromatography to give 3-hydroxy-3-(phenylethynyl)indolin-2-ones (3a-3u).

According to the analysis of related databases, 60434-13-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Paplal, Banoth; Sathish, Kota; Nagaraju, Sakkani; Kashinath, Dhurke; Catalysis Communications; vol. 135; (2020);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 20870-90-0, The chemical industry reduces the impact on the environment during synthesis 20870-90-0, name is 5-Bromo-1-methyl-2-oxoindoline, I believe this compound will play a more active role in future production and life.

A mixture of 5-bromo-N-methyloxindole(5 g, 22 mmol) and POCl3 (40 mL) was stirred and refluxed for 2h. After cooling, themixture was poured into ice water, and then extracted with dichloromethane (MC) forthree times. The combined organic layers were dried over anhydrous magnesium sulfate,filtered, and concentrated. The solid was washed with MC, white solid NMT (2.6 g) wasprepared. Yield was 61%.1H-NMR (300MHz, THF) delta(ppm) : 8.58 (s, 3H), 7.63-7.60 (d, 3H), 7.57-7.53 (d, 3H),4.40 (s, 9H).

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-Bromo-1-methyl-2-oxoindoline, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Kang, Hyeonmi; Lee, Hayoon; Shin, Hwangyu; Kang, Seokwoo; Kim, Beomjin; Park, Jongwook; Molecular Crystals and Liquid Crystals; vol. 618; 1; (2015); p. 47 – 54;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 141452-01-9, 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. 141452-01-9 name is Methyl indoline-5-carboxylate, 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.

(R)-l-(4-cyclopentyl-3-ethyl-l-methyl-2-oxo-l,2,3,4-tetrahydropyrido[2,3-6]pyrazin-6- yl)indoline-5-carboxylic acid (i?)-6-chloro-4-cyclopentyl-3-ethyl-l-methyl-3,4-dihydropyrido[2,3-]pyrazin- 2(lH)-one (20.2 mg, 0.0688 mmol, 1 eq), methyl indoline-5-carboxylate (14.6 mg, 0.0825 mmol, 1.2 eq), Pd2dba3 (3.2 mg, 0.00344 mmol, 5 mol%), XPhos (4.9 mg, 0.0103 mmol, 15 mol%) and K2C03 (38 mg, 0.275 mmol, 4 eq) were dissolved in tBuOH (0.69 mL, 0.1 M) and heated to 100 C for 18 hours. The mixture was filtered through celite, washed with DCM/EtOAc/MeOH and condensed. Purification by column chromatography (ISCO, 4 g silica column, 0-10%MeOH/DCM, 15 minute gradient) gave a mixture of the desired methyl ester and the (inconsequential) ethyl ester, which was used without further purification (29.64 mg). LCMS 434.48 (M+H), 449.47 (ethyl ester M+H). The resulting material was dissolved in THF (0.34 mL) and water (0.17 mL). LiOH (2.4 mg) was added and the mixture was stirred at room temperature. Due to poor solubility and sluggish conversion, an additional 2.4 mg LiOH, 0.17 mL water and 0.17 mL MeOH were added. After 2 days, the mixture was diluted with MeOH and purified by preparative HPLC to give a dark brown oil (16.78 mg, 0.0399 mmol, 59% over 2 steps. 1H NMR (400 MHz, Chloroform-;/) delta 8.10 (d, J= 8.6 Hz, 1H), 7.83 (dd, J= 8.6, 1.7 Hz, 1H), 7.79 – 7.74 (m, 1H), 7.16 – 7.1 1 (m, 1H), 6.21 (d, J= 8.4 Hz, 1H), 4.62 – 4.54 (m, 1H), 4.13 – 4.00 (m, 3H), 3.31 – 3.30 (m, 3H), 3.20 (t, J = 8.7 Hz, 2H), 2.14 – 2.04 (m, 2H), 1.80 – 1.54 (m, 8H), 0.86 (td, J = 7.6, 2.8 Hz, 3H). LCMS 421.51 (M+H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl indoline-5-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; BRADNER, James, E.; GRAY, Nathanael; QI, Jun; MCKEOWN, Michael, R.; BUCKLEY, Dennis; WO2015/117055; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 20870-79-5,Some common heterocyclic compound, 20870-79-5, name is 5-Nitroindolin-2-one, molecular formula is C8H6N2O3, 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.

Preparation of 5-amino-oxindole (2) To a solution of 5-nitro-oxindole (25 g) in 120 mL of dimethylacetamide in a Parr bottle was added 10% Pd/C (0.5 g). The mixture was hydrogenated (40 psi H2) for 16 hours. The catalyst was removed by filtration and the filtrate was diluted with ether (2 L) to provide 5-amino-oxindole (10.5 g; 50%).

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

Reference:
Patent; Pfizer Inc; US2005/256145; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem