Category: indolines-derivatives

Application of 13220-46-7, 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. 13220-46-7 name is 4-Methylindolin-2-one, 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.

5-Chloro-4-methyl-2-oxindole A suspension of 3.0 g of 4-methyl-2-oxindole was stirred in 50 mL of acetonitrile at room temperature while 3.3 g of N-chlorosuccinimide was added in portions. Trifluoroacetic acid (1 mL) was then added. The suspension was stirred at room temperature for 3 days during which time solid was always present. The white solid was collected by vacuum filtration, washed with a small amount of cold acetone and dried overnight in a vacuum oven at 40 C. to give 2.5 g (68%) of 5-chloro-4-methyl-2-oxindole.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Methylindolin-2-one, and friends who are interested can also refer to it.

Reference:
Patent; Sugen, Inc.; US6878733; (2005); B1;,
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Related Products of 264916-06-5, 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. 264916-06-5, name is tert-Butyl 5-aminoisoindoline-2-carboxylate belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a cooled solution of 2.0 M of lithium tetrahydroborate in tetrahydrofuran (13 mL, 26 mmol) at 5C was added dropwise a solution of 5-amino-l,3-dihydro-isoindole-2- carboxylic acid tert-butyl ester (1.0 g, 4.3 mmol) in tetrahydrofuran (50 mL). Gas evolution was noted. The mixture was stirred for 1 hour at 5C then warmed to room temperature and stirred for 24 hours. The mixture was cooled to 5C in a ice/water bath and the reaction was quenched by addition of sodium sulfate decahydrate (3 g). Gas evolution noted. The mixture was stirred for 2 hours at room temperature. The suspension was filtered through a plug of diatomaceous earth and rinsed with with tetrahydrofuran. The filtrate was dried over magnesium sulfate, filtered and evaporated. The residue was purified via flash chromatography (silica gel column and 0%?20% methanol: dichloromethane). 2-Methyl-2,3-dihydro-lH-isoindol-5-ylamine was isolated as an orange solid (0.271 g, 43%). 1H NMR (400 MHz, (D3C)2SO, delta, ppm): 6.82 (d, J=I .9 Hz, IH), 6.41 (s, IH), 6.37 (d, J=8.1 Hz, IH), 4.86 (br s, 2H), 3.64 (s, 2H), 3.62 (s, 2H), 2.42 (s, 3H). MS = 149 (MH)+.

The synthetic route of tert-Butyl 5-aminoisoindoline-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CEPHALON, INC.; CURRY, Matthew A.; DORSEY, Bruce D.; DUGAN, Benjamin J.; GINGRICH, Diane E.; MESAROS, Eugen F.; MILKIEWICZ, Karen L.; WO2010/141796; (2010); A2;,
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Application of 112656-95-8,Some common heterocyclic compound, 112656-95-8, name is 7-Nitroindoline-2,3-dione, molecular formula is C8H4N2O4, 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.

The solution of 7-nitro-isatin (15) (3 g, 0.016 mol), cyanoacetic acid (1.33 g, 0.016 mol) and piperidine (0.10 ml) in pyridine (15 ml) was refluxed for 30 hours. After cooling to room temperature, concentrated hydrochloric acid (1 ml) and water (10 ml) were added. The product was obtained by extraction with ethylacetate. Organics were dried under sodium sulfate, solvent was removed in vacuum to give 2 g (60 % yield) of (7-nitro-2-oxindole-3-yliden)acetonitrile. mp (exp.) = 224-225 0C. Spectrum NMR 1 (DMSO-d6, delta, ppm, J, Hz): 6.94 (s, 1H), 7.28 (dd, J = 7.45; J = 8.34, 1H); 7.86 (d, J = 7.20, 1H), 8.10 (d, J = 8.59, 1H), 11.33 (s, 1H). Spectrum NMR 13C (DMSO-d6, delta, ppm): 70.99; 117.17; 122.89; 125.25; 130.77; 131.62; 133.82; 138.63; 177.50. IR spectrum (sm-1): 1535; 1598; 1626 (NO2), 1727 (C=O), 2926; 2958 (C=C-H), 3239; 3348 (NH). MS (EI, 70 eV), m/z (I, %): 233 (77, [M*H2O]+), 215 (26, M+), 193 (86), 189 (44), 175 (50), 149 (32), 145 (60), 118 (70), 90 (31), 63 (31), 41 (40), 30 (100).

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

Reference:
Article; Zaryanova, Ekaterina V.; Lozinskaya, Nataly A.; Beznos, Olga V.; Volkova, Maria S.; Chesnokova, Nataly B.; Zefirov, Nikolay S.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 16; (2017); p. 3787 – 3793;,
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Related Products of 100510-65-4, A common heterocyclic compound, 100510-65-4, name is 6-Amino-3,3-dimethylindolin-2-one, molecular formula is C10H12N2O, 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 solution of compound 8 (100 mL, compound 7, 23.7 mmol from 5.3 g) at 0 to 5 degrees, a methylene chloride solution of compound 23 (4.0 g, 18.8 mmol) and triethylamine (2.6 mL, 18.8 mmol) was added dropwise. The reaction solution was stirred at room temperature overnight, washed with aqueous sodium bicarbonate solution, washed with water, the organic phase was concentrated under reduced pressure, filtered, and the filter cake was washed with a small amount of dichloromethane, and dried in vacuo to give an off-white solid compound 24 (5.2 g, yield 65.7%).

The synthetic route of 100510-65-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Suzhou Ruiming Drug Discovery Co., Ltd.; Zhang Fei; Feng Zixia; (33 pag.)CN110950868; (2020); A;,
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Synthetic Route of 17564-64-6, 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. 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of phthalimide (41.14 g, 0.30 mol) and distilled water (100 mL) was stirred for 10 min at room temperature. After addition of formaldehyde solution (40%, 27 mL, 0.36 mol), the resulting solution was refluxed for 1.5 h. After cooling to 0-5 C, the resulting precipitate was collected by filtration, washed with cold water (0-5 C, 200 mL) and dried in air to give the corresponding N-hydroxymethylphthalimide (51.01 g, 96% yield).(0010)A solution of thionyl chloride (23.0 mL, 37.7 g, 0.32 mol) in dichloromethane (50 mL) was slowly added to a mixture of the resulting N-hydroxymethylphthalimide and dichloromethane (550 mL) and N,N-dimethylformamide (350 mL) during 30 min at room temperature with stirring. The resulting mixture was further stirred for 2 h at room temperature. After cooling to 0 C, water (200 mL) was added slowly. And the solution was neutralized to pH 6.7-7.0 by using saturated aqueous NaHCO3 solution. The organic layer was separated and then was dried over anhydrous magnesium sulfate. After evaporation of the solvent under the reduced pressure, the residue was washed with n-hexane (100 mL) to give N-chloromethylphthalimide (51.4 g, 93% yield).(0011) N-Chloromethylphthalimide (51.0 g, 0.26 mol) was dissolved in acetone (500 mL) and potassium O-ethyl xanthate (43.9 g, 274 mmol) was added portionwise in an ice water bath under stirring. The resulting solution was further stirred for 10 h at room temperature. After removal of the solvent, the residue was dissolved in dichloromethane. The resulting solution was washed with water and dried over sodium sulfate. After removal of the solvent under the reduced pressure, pale yellow solid was obtained and recrystallized from ethyl acetate to afford the xanthate 1 as colorless crystals 67.2 g, 92% yield, mp: 99-100 C. Lit.20 mp: 94-95 C. 1H NMR (CDCl3, 400 MHz) (delta, ppm) 1.47 (t, J=7.1 Hz, 3H, CH3), 4.68 (q, J=7.1 Hz, 2H, CH2), 5.34 (s, 2H, CH2), 7.75 (dd, J=5.5, 3.1 Hz, 2H, ArH), 7.88 (dd, J=5.5, 3.1 Hz, 2H, ArH). 13C NMR (CDCl3, 100 MHz) (delta, ppm) 13.7, 41.2, 70.5, 123.6, 131.8, 134.4, 166.6, 210.2.

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

Reference:
Article; Huang, Zhongyan; Xu, Jiaxi; Tetrahedron; vol. 69; 3; (2013); p. 1050 – 1056;,
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These common heterocyclic compound, 550-44-7, name is 2-Methylisoindoline-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. Application In Synthesis of 2-Methylisoindoline-1,3-dione

Add a nitrating agent to N-methylphthalimide at -5 C, and react at 40 C for 4h, then extract with an extraction solvent dry,N-methyl-4-nitrophthalimide is formed.The extraction solvent is ethyl acetate and dichloromethane, and the weight ratio is 1: 0.6. The weight ratio of the extraction solvent and N-methylphthalimide is 1: 1.

The synthetic route of 2-Methylisoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shandong Juancheng Fangyuan Bearing Chemical Co., Ltd.; Li Zhi; Zhang Hongyuan; Zhang Heji; (13 pag.)CN110437131; (2019); A;,
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Adding a certain compound to certain chemical reactions, such as: 675109-26-9, name is 6-Bromoisoindolin-1-one, 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 675109-26-9, Quality Control of 6-Bromoisoindolin-1-one

A mixture of 6-bromoisoindolin-i-one (5 g, 23.6 mmol), sodium azide (3.07 g, 47.2 mmol), sodium ascorbate (234 mg, 1.18 mmol), Cul (450 mg, 2.36 mmol) and trans-N,N-dimethyl- 1 ,2-diaminocyclohexane (504 mg, 3.54 mmol) in ethanol (35 mE) and water (15 mE) was stirred at reflux for 5.5 h under nitrogen. The reaction mixture was allowed to cool to room temperature and extracted with EtOAc (100 mEx3). The combined organic fractions were washed with brine and dried with anhydrous sodium sulfate.The solvent was evaporated under reduced pressure and the residue was purified by chromatography on silica gel (10- 50% EtOAc in pet. ether) to give iSA (1.2 g, 29% yield) as an off-white solid. ESI mlz 175.0 [M+i].

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromoisoindolin-1-one, and friends who are interested can also refer to it.

Reference:
Patent; Seal Rock Therapeutics, Inc.; BROWN, Samuel David; US2018/291002; (2018); A1;,
Indoline – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-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 2058-72-2, Computed Properties of C9H6BrNO2

General procedure: To a stirring mixture of catalyst 1a (0.005 mmol) and cyclohexanone/acetone (5 mmol) in water (500 muL), additive DNP (0.920 mg, 0.005 mmol) was added at 25 C and the mixture was allowed to stir for 5 min followed by addition of isatin derivative (0.5 mmol). The mixture was stirred for 20-96 h and the progress of the reaction was monitored at regular intervals by TLC. On the completion of reaction, saturated solution of NH4Cl (5 mL) was added to it and resulting mixture was extracted with ethyl acetate (3×15 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain crude aldol product. The column chromatography on silica gel (60-120 mesh) using hexane/ethyl acetate as an eluent gave the corresponding aldol adducts as a syn/anti mixture. The enantiomeric excess of aldol addition products was determined by chiral HPLC. The diastereoselectivity of product was determined by HPLC of crude reaction mixture. Racemic standards were prepared using (±) 3-methyl-1-morpholinobutan-2-amine catalyst synthesized form (±) valine.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Article; Kumar, Akshay; Chimni, Swapandeep Singh; Tetrahedron; vol. 69; 25; (2013); p. 5197 – 5204;,
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169037-23-4, name is 5-(Trifluoromethoxy)indoline-2,3-dione, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Computed Properties of C9H4F3NO3

General procedure: The title compound was synthesized in one step from commercially available starting materials according to the following procedure. Into a 20mL microwave reaction vial, containing a magnetic stir bar, were weighed 5-(trifluoromethoxy)isatin (460mg, 2.0mmol), K2CO3 (550mg, 4.0mmol), KI (33mg, 0.20mmol), followed by acetonitrile (20mL, 0.1M) and 2-bromoethyl phenyl ether (480mg, 2.4mmol). After being sealed with a crimp cap, the vessel was placed in a microwave reactor and heated to 160C for 10min, with magnetic stirring. After cooling to ambient temperature, the reaction was diluted with CH2Cl2 (?20mL) and washed with brine. The organic layer was separated and dried over Na2SO4. Solvent was removed under reduced pressure and the crude product was purified via flash column chromatography (silica gel, hexane/ethyl acetate, 0-50% ethyl acetate gradient). Product containing fractions were combined and the solvents removed under reduced pressure to obtain 583mg of ML326 (83% yield) as a red-orange powder. TLC Rf=0.79 (hexane/ethyl acetate 1:1); 1H NMR (400MHz, CDCl3 calibrated to 7.26) delta 7.52-7.46 (m, 2H), 7.31-7.25 (m, 3H), 6.98 (t, J=7.4Hz, 1H), 6.82 (d, 2H), 4.28 (t, J=5.0Hz, 2H), 4.17 (t, J=5.0Hz, 2H); 13C NMR (125MHz, CDCl3 calibrated to 77.16) delta 182.25, 158.27, 157.93, 150.01, 145.44, 131.02, 129.78, 121.75, 118.32, 114.39, 112.89, 65.94, 40.62; HRMS calcd for C17H13NO4F3[M+H+]; 352.0797 found: 352.0795.

The synthetic route of 169037-23-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Gentry, Patrick R.; Bridges, Thomas M.; Lamsal, Atin; Vinson, Paige N.; Smith, Emery; Chase, Peter; Hodder, Peter S.; Engers, Julie L.; Niswender, Colleen M.; Scott Daniels; Jeffrey Conn; Wood, Michael R.; Lindsley, Craig W.; Bioorganic and Medicinal Chemistry Letters; vol. 23; 10; (2013); p. 2996 – 3000;,
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Related Products of 5428-09-1, The chemical industry reduces the impact on the environment during synthesis 5428-09-1, name is 2-Allylisoindoline-1,3-dione, I believe this compound will play a more active role in future production and life.

Under argon, a solution of [5-(4-bromo-2,6-dimethyl-phenyl)-[1,2,4]triazin-3-yl]-(5-methoxy-benzothiazol-2-ylmethyl)-amine (46 mg, 0.1 mmol, prepared as in example 79), N-allyl phtalimide (22.5 mg, 0.12 mmol, prepared as in Tetrahedron 2006, 62, 12247), triethylamine (28 muL, 0.2 mmol), tri-o-tolylphosphine (3.6 mg, 0.012 mmol), palladium(II) acetate (1.4 mg, 0.006 mmol) in degassed anhydrous acetonitrile (0.2 mL) was stirred at 100°C overnight. The reaction mixture was filtered over a pad of celite, rinsed with dichloromethane, methanol, ethyl acetate, and evaporated. The crude product was purified by preparative TLC (silica gel, dichloromethane/methanol 95/5) to afford 2-[3-(4-{3-[(5-methoxy-benzothiazol-2-ylmethyl)-amino]-[1,2,4]triazin-5-yl}-3,5-dimethyl-phenyl)-allyl]-isoindole-1,3-dione (43 mg, 76percent) as a beige solid. ESI-MS m/z 563 (M+H)+.

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-Allylisoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Mutabilis; EP2141164; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem