Category: indolines-derivatives

Synthetic Route of 14389-06-1, A common heterocyclic compound, 14389-06-1, name is 5-Chloro-7-methylindoline-2,3-dione, molecular formula is C9H6ClNO2, 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: To a mixture of 5-chloroisatin (182 mg, 1.0 mmol) and N-carboxyethylrhodanine (205 mg, 1.0 mmol) was added DMSO-d6 (3.0 mL). The reaction was followed by proton NMR until the disappearance of the starting material.

The synthetic route of 14389-06-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Xue, Fengtian; MacKerell Jr., Alexander D.; Heinzl, Geoffrey; Hom, Kellie; Tetrahedron Letters; vol. 54; 13; (2013); p. 1700 – 1703;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 102359-00-2, The chemical industry reduces the impact on the environment during synthesis 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, I believe this compound will play a more active role in future production and life.

2-Oxoindoline-5-carboxylic acid (0.470 g, 2.66 mmol), O-(benzotriazol-1-yl)-N,N,N’,N’- TETRAMETHYLURONIUM TETRAFLUOROBORATE (1. 010 g, 3.15 mmol), 1-hydroxybenzotriazole hydrate (0.417 g, 3.09 mmol) and N, N-diisopropylethylamine (0.7 ML, 4.0 mmol) were suspended in ACETONITRILE/N-DIMETHYLFORMAMIDE, (10 mL: 2 mL), and stirred at room temperature for 30 min. 2-Methoxyethanamine (0.516 g, 6.88 mmol) was added and stirring was continued for 2 h. Saturated aqueous sodium hydrogencarbonate was added (10 mL) and the solvents were removed M vacuo. The residue was purified on a silica gel column using a gradient chloroform/methanol, (100: 1 to 1: 1), as the eluent to give 0.355 g (57% yield) of the title compound as a solid : 1H NMR (DMSO-DE, 400 MHz) 8 10.59 (s, 1 H), 8.31 (m, 1 H), 7.72 (d, J = 7 Hz, 1 H), 7.71 (s, 1 H), 6.83 (d, Y= 8 HZ, 1 H), 3.51 (s, 2 H), 3.42 (m, 2 H), 3.39 (m, 2 H), 3.24 (s, 3 H); MS (ES) TIL/Z 235 (M++1).

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-Oxoindoline-5-carboxylic Acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ASTRAZENECA AB; WO2005/27823; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 6341-92-0, 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. 6341-92-0, name is 6-Chloroisatin belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 39a rac-6-Chloro-3-hydroxy-3-pyridin-3-yl-1,3-dihydro-indol-2-one To a solution of n-butyllithium (2.0 M in hexanes, 3.45 mL, 7.5 mmol) (Aldrich) in tetrahydrofuran (3 mL) at -78 C. was added a solution of 3-bromo-pyridine (0.96 g, 8.1 mmol) (Aldrich) in tetrahydrofuran (6 mL) dropwisely. After the addition, the resulting dark solution was stirred for additional 15 minutes. A solution of 6-chloroisatin (0.5 g, 2.76 mmol) (Crescent) in tetrahydrofuran (5 mL) was added dropwisely and the crude was warmed up to room temperature and stirred at room temperature for 3 hours. The reaction was quenched with water. The mixture was extracted with ethyl acetate three times. The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated. The residue was purified by chromatography to give rac-6-Chloro-3-hydroxy-3-pyridin-3-yl-1,3-dihydro-indol-2-one as a yellow solid. (Yield 0.27 g, 37%).

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, 6-Chloroisatin, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Luk, Kim-Chun; So, Sung-Sau; Zhang, Jing; Zhang, Zhuming; US2006/293319; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 3676-85-5, name is 5-Aminoisoindoline-1,3-dione, molecular formula is C8H6N2O2, 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. COA of Formula: C8H6N2O2

To 100 parts of nitrobenzene,4-aminophthalimide10 parts,And cyanuric chloride11 parts were added,And heated at 100 to 110 C. for 5 hours.After cooling it was filtered,Washed with methanol and water.And dried at 80 C. to obtain a compound represented by the formula (2)To obtain 17 parts of the intermediate (2) represented.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3676-85-5, its application will become more common.

Reference:
Patent; DAINICHISEIKA COLOR & CHEMICALS MANUFACTURING COMPANY LIMITED; IGUCHI, KAZUKI; YANAGIMOTO, HIROMITSU; (19 pag.)JP5823431; (2015); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 825-70-7, name is 5-Fluoro-2-methylindoline, 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 825-70-7, Computed Properties of C9H10FN

Example 13c and Example 14c Synthesis of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one and of (-)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one 430 mg of 5-fluoro-2-methyl-2,3-dihydro-1H-indole (reference example 4c, step 1c) and 872 mg of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride are added to a solution of 743 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2c of example 1c) in 25 ml of N,N-dimethylformamide and 25 ml of pyridine. The reaction mixture is stirred at ambient temperature for 48 hours and then 100 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with a 0.1N hydrochloric acid solution, water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol (95/05: v/v), so as to give 580 mg of 2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one.The enantiomers are separated by chiral chromatography on a Whelk 01 SS, 10 mum column (10 mum, 80×350 mm), elution being carried out with a mixture of: heptane/dichloromethane/ethanol/methanol: 70/20/5/5; flow rate: 200 ml/min.252 mg of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained, as first enantiomer, in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.26 (d, J=6.4 Hz, 3H); 2.70 (m, 1H); 3.34 to 3.48 (m, 5H); 3.60 (m, 4H); 3.71 (d, J=15.9 Hz, 1H); 3.91 (d, J=15.9 Hz, 1H); 4.73 (m, 1H); 5.20 (s, 1H); 7.00 (dt, J=3.0 and 9.1 Hz, 1H); 7.15 (dd, J=3.0 and 9.1 Hz, 1H); 7.95 (dd, J=5.0 and 9.1 Hz, 1H); 11.65 (broad m, 1H)Mass spectrometry: method ARetention time Tr (min)=0.72;[M+H]+: m/z 373; [M-H]-: m/z 371;Optical rotation: alphaD=+60.4 (c=1.939 mg/0.5 ml CH3OH)Then the second enantiomer, 246 mg of (-)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one, is obtained in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.26 (d, J=6.5 Hz, 3H); 2.69 (m, 1H); 3.35 to 3.47 (m, 5H); 3.60 (m, 4H); 3.71 (d, J=15.9 Hz, 1H); 3.91 (d, J=15.9 Hz, 1H); 4.72 (m, 1H); 5.20 (s, 1H); 7.00 (td, J=3.0 and 9.1 Hz, 1H); 7.15 (dd, J=3.0 and 9.1 Hz, 1H); 7.95 (dd, J=5.0 and 9.1 Hz, 1H); 11.66 (broad m, 1H)Mass spectrometry: method ARetention time Tr (min)=0.72;[M+H]+: m/z 373; [M-H]-: m/z 371;Optical rotation: alphaD=-57.9+/-1.1 (c=1.833 mg/0.5 ml CH3OH)

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:
Patent; SANOFI; Brollo, Maurice; Carry, Jean-Christophe; Certal, Victor; Didier, Eric; Doerflinger, Gilles; EL Ahmad, Youssef; Filoche-Romme, Bruno; Halley, Frank; Karlsson, Karl Andreas; Schio, Laurent; Thompson, Fabienne; US2013/274253; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 446292-08-6,Some common heterocyclic compound, 446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, molecular formula is C22H19N3O6, 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.

20.0 g (23.80 mmol) of (5)-2-({2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-l,3- oxazolidin-5-yl}methyl)-lH-isoindole-l,3(2H)-dione (compound III, obtained from compound II following the process disclosed in the ‘823 patent) were suspended in 600 mL of acetonitrile and cooled to 0 C. A solution of 3.6 g (7.20 mmol) of sodium sulfide in 60 mL of water was added dropwise to the suspension over 1 hour. The reaction mixture was then stirred for 30 minutes between 5-10 C. The pH was adjusted to 7 using 1.5 M hydrochloric acid solution whilst maintaining the temperature at 5-10 C. The mixture was filtered and 40.0 g of sodium chloride were added to the filtrate. The aqueous phase was collected and kept aside. The organic phase and the solid obtained from the filtration were loaded into the reactor and cooled to 0 C. A solution of 3.6 g (7.20 mmol) of sodium sulfide in 60 mL of water was added dropwise to the suspension over 1 hour. The reaction mixture was then stirred for 30 minutes between 5-10 C. The pH was adjusted to 7 using 1.5 M hydrochloric acid solution whilst maintaining the temperature at 5-10 C. The mixture was filtered and 40.0 g of sodium chloride were added to the filtrate. The aqueous phase was collected and combined with the previous one which was kept aside. The combined aqueous phase was cooled to 0 C. The pH was adjusted to 4-5 using 1.5 M hydrochloric acid solution whilst maintaining the temperature at 5-10 C. 40.0 g of sodium chloride were added and the solution was extracted twice with 600 mL of acetonitrile. The combined organic phases were dried with 60 g of anhydrous sodium sulfate, filtered and concentrated under vacuum without exceeded 38 C . 1 1 .0 g of (5)-2-[({2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-l,3- oxazolidin-5-yl}methyl)carbamoyl]benzoic acid (compound V) were obtained as a pale yellow foam-like solid. Yield: 56.0 %. HPLC chromatographic purity: 95.29% (% area).

The synthetic route of 446292-08-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDICHEM S.A.; MANGION, Bernardino; DURAN LOPEZ, Ernesto; WO2012/35057; (2012); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 603-62-3, 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. 603-62-3 name is 3-Nitrophthalimide, 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.

Step 1): An ice cooled solution of bromine (2.5 ml, 48.5 mmol) in 1N KOH aq.solution was added to the solution of 3-nitrophthalimide (9.66 g, 50 mmol) in 1N KOH aq.solution (150 ml) followed by 1N KOH at 0. The mixture was refluxed for 1.5 hours. After cooling, the mixture was neutralized with 2N HCl and stirred at 0 to precipitate 2-amino-6-nitrobenzoic acid, 6.23 g (68%): mp 190 C.

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

Reference:
Patent; Grelan Pharmaceutical Co. Ltd.; Laboratoires Fournier S.C.A.; US5872115; (1999); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, 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. Recommanded Product: 2-Oxoindoline-5-carboxylic Acid

To A NN-DIMETHYLFORMAMIDE/ACETONITRILE, (2 mL: 10 mL), mixture containing ethyldiisopropylamine (0.52 ML, 3 mmol) was added 2-oxoindoline-5-carboxylic acid (0.354 g, 2.0 mmol; described in: Sun L. et al. J. MED. Chem. 2000, 43 (14), 2655:), O- (BENZOTRIAZOL-1-YL)-N, N, N, N-TETRAMETHYLURONIUM tetrafluoroborate (0.77 g, 2.4 mmol) and 1-HYDROXYBENZOTRIAZOLE hydrate (0.324 g, 2.4 mmol) and stirred for 5 min at room temperature. Thereafter, 2- (AMINOMETHYL) pyridine (0.562 g, 5.2 mmol) was added and the resulting reaction mixture was stirred for 90 min followed by addition of a saturated aqueous NAHCO3 solution (10 ML). The solvents were removed in vacuo and 0.364 g (68% yield) of the title product was obtained as a white solid after purification on a silica gel column using chloroform/methanol, (9: 1), as the eluent : 1H NMR (DMSO-d6, 400 MHz) 8 10. 66 (s, 1 H), 8.96 (t, 7= 5. 6 HZ, 1 H), 8.55 (d, J = 4.4 Hz, 1 H), 7. 85 (d, J = 8. 0 HZ, I H), 7.83 (s, 1 H), 7. 78 (t, J = 7.6 Hz, 1 H), 7.34 (d, J = 8.0 Hz, 1 H), 7.29 (t, J= 6. 4 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 4.59 (d, J = 6.0 Hz, 2 H), 3. 58 (s, 2 H); MS (EI) MLZ 268 (M++1).

The synthetic route of 2-Oxoindoline-5-carboxylic Acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WO2005/27823; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 20870-78-4,Some common heterocyclic compound, 20870-78-4, name is 5-Bromoindolin-2-one, molecular formula is C8H6BrNO, 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 10 ml schlenk bottle by adding 5 – bromo -2 – indolone (1 a, 0.3 mmol), tert-butyl nitrite (t – BuONO, 2 a, 0.6 mmol) and THF (2 ml), then oxygen atmosphere (1 atm) next, the reactor is placed 25 C stirring under the conditions of reaction, monitoring the reaction by TLC or GC process, to the reaction raw material 5 – bromo -2 – indolone reaction is complete, to stop the reaction, the reaction the fluid uses full and salt water washing, recovering the organic phase, the aqueous phase is extracted with ethyl acetate, the combined organic phase; organic phase was dried with anhydrous sodium sulfate, filtered, distilled under reduced pressure, the residue by column chromatography (petroleum ether/ethyl acetate) separation to obtain the target product 5 – […], I – 6, the isolation yield is 76%

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

Reference:
Patent; Ningbo University; Huang Yiling; Wei Wenting; Ying Weiwei; Wu Yi; Wu Kewei; Cao Yiqi; Wang Yining; Zhu Liwei; (8 pag.)CN107141246; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 3484-35-3,Some common heterocyclic compound, 3484-35-3, name is 5-Methylindolin-2-one, molecular formula is C9H9NO, 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.

4-(2-Carboxyethyl)-2-formyl-3-methylpyrrole (90 mg), 74 mg 5-methyl-2-oxindole, and 75 muL piperidine in 2 mL of ethanol were heated at 95 C. for 5 hours. The reaction mixture was cooled and concentrated. The residue was suspended in 6 N aqueous hydrochloric acid. The precipitate was filtered, washed with water to pH 6 and dried in a vacuum oven to give 65 mg (42%) of the title compound as a brown solid. 1H-NMR (360 MHz, DMSO-d6): delta 13.30 (s, br, 1H, NH-1′), 12.05 (s, br, 1H, COOH), 10.67 (s, br, 1H, NH-1), 7.57 (s, 2H, H-vinyl, H-4), 7.12 (d, J=2.65 Hz, 1H, H-2′), 6.91 (d, J=7.82 Hz, 1H, H-6), 6.74 (d, J=7.82 Hz, 1H, H-7), 2.65 (t, J=6.94 Hz, 2H, CH2CH2COOH), 2.46 (t, J=6.94 Hz, 2H, CH2CH2COOH), 2.30 (s, 3H, CH3), 2.25 (s, 3H, CH3); MS m/z (relative intensity, %), 311 ([M+1]+, 100).

The synthetic route of 3484-35-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sugen, Inc.; US6878733; (2005); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem