Author: Jessica.F

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. 59-48-3, name is Indolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Product Details of 59-48-3

5-(Bromo)-1,3-dihydro-indol-2-one A solution of oxindole (2.0 g, 15.0 mmol) and sodium acetate (2.1 g, 25.5 mmol) in CHCl3 (20 cm3) was treated with bromine (2.4 g, 15.0 mmol) in CHCl3 (10 cm3). After 30 min. the mixture was allowed to warm to RT and stirred for 1 h. The reaction mixture was diluted with EtOAc (500 cm3) and poured into water. The aqueous layer was extracted with EtOAc (*2), the combined organic layers were washed with water, sat. sodium hydrogen carbonate solution, brine, dried (MgSO4), and evaporated to give the title compound (3.1 g, 14.6 mmol, 96 %) as an off-white solid which was used without further purification: mp. 221-223 C.; 1H NMR (DMSO-d6) delta3.51 (s, 2H), 6.76 (d, 1H, J=8.1 Hz), 7.33(dd, 1H, J=8.1, 1.7 Hz), 7.37 (s, 1H), 10.49 (br s, 1H); 13C NMR (DMSO-d6) delta36.10 (t), 111.21 (d), 113.16 (s), 127.54 (d), 128.3 (s), 130.40 (d), 143.34 (s), 176.24 (s); MS (EI) m/z 211, 213 (M)+.

The synthetic route of 59-48-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; American Home Products Corporation; Ligand Pharmaceuticals, Inc.; US6391907; (2002); B1;,
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Reference of 2058-72-2, 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. 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: A mixture of compound 3 (1 mmol) and the appropriate isatinderivative 4a-i (1 mmol) in absolute ethyl alcohol and catalyticamount of glacial acetic acid was heated under reflux for 4 hrs,filtered while hot and the collected solid was washed with ethanol.The crude products 5a-i were re-crystallized from ethanol/DMFmixture (3:1) to furnish the pure title compounds 5a-i in 43-94%yields.

The chemical industry reduces the impact on the environment during synthesis 5-Bromo-1-methylindoline-2,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Article; Almutairi, Maha S.; Zakaria, Azza S.; Ignasius, P. Primsa; Al-Wabli, Reem I.; Joe, Isaac Hubert; Attia, Mohamed I.; Journal of Molecular Structure; vol. 1153; (2018); p. 333 – 345;,
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Indoline | C8H9N – PubChem

Reference of 825-70-7, These common heterocyclic compound, 825-70-7, name is 5-Fluoro-2-methylindoline, 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 15c and Example 16c Synthesis of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-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}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one 430 mg of 5-fluoro-2-methyl-2,3-dihydro-1H-indole (reference example 4c) and 872 mg of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride are added to a solution of 1.1 g of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate 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 538 mg of 2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-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¡Á350 mm), elution being carried out with a mixture of: heptane/dichloromethane/ethanol/methanol: 60/20/10/10; flow rate: 240 ml/min.212 mg of (+)-2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-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): 1.28 (d, J=6.6 Hz, 3H); 2.70 (d, J=16.2 Hz, 1H); 3.33 (s, 3H); 3.36 to 3.44 (m, 5H); 3.58 (m, 4H); 4.02 (d, J=16.6 Hz, 1H); 4.27 (d, J=16.6 Hz, 1H); 4.73 (m, 1H); 5.36 (s, 1H); 7.00 (td, J=2.9 and 8.9 Hz, 1H); 7.16 (dd, J=2.9 and 8.9 Hz, 1H); 7.94 (dd, J=5.0 and 8.9 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.76;[M+H]+: m/z 387; [M-H]-: m/z 385;Optical rotation: alphaD=+72.0 (c=1.704 mg/0.5 ml CH3OH)Then the second enantiomer (Tr=17.61 min), 210 mg of (-)-2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-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): 1.28 (d, J=6.4 Hz, 3H); 2.70 (d, J=16.2 Hz, 1H); 3.33 (s, 3H); 3.37 to 3.44 (m, 5H); 3.59 (m, 4H); 4.02 (d, J=16.6 Hz, 1H); 4.27 (d, J=16.6 Hz, 1H); 4.72 (m, 1H); 5.36 (s, 1H); 7.00 (td, J=3.0 and 8.8 Hz, 1H); 7.16 (dd, J=3.0 and 8.8 Hz, 1H); 7.93 (dd, J=5.1 and 8.8 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.76;[M+H]+: m/z 387; [M-H]-: m/z 385;Optical rotation: alphaD=-59.5 (c=2.182 mg/0.5 ml CH3OH)

The synthetic route of 825-70-7 has been constantly updated, and we look forward to future research findings.

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

Some common heterocyclic compound, 20870-90-0, name is 5-Bromo-1-methyl-2-oxoindoline, molecular formula is C9H8BrNO, 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. Quality Control of 5-Bromo-1-methyl-2-oxoindoline

EXAMPLE 59A benzyl 1-methyl-oxindole-5-carboxylate A solution of 5-bromo-1-methyl oxindole (3.75 g, 16.6 mmol) and triethylamine (3.48 mL) in THF (40 mL) was treated with benzyl alcohol (2.58 mL) and PdCl2(dppf) (300 mg), stirred under carbon monoxide (680 psi) at 130 C. for 16 hours, depressurized, filtered through diatomaceous earth (Celite), and concentrated. The concentrate was purified on silica gel with 30% ethyl acetate/hexanes to provide 2.36 g of the desired product. MS (ESI(+)) m/z 299 (M+NH4)+; 1H NMR (CDCl3) delta 8.10-8.07 (m, 1H), 7.95 (s, 1H), 7.47-7.33 (m, 5H), 6.86 (d, J=8.1 Hz, 2H), 5.35 (s, 2H), 3.56 (s, 2H), 3.25 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 20870-90-0, its application will become more common.

Reference:
Patent; Abbott Laboratories; US6228868; (2001); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 3676-85-5, 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 3676-85-5 as follows.

6: A suspension of 4-amino-phthalimide 5 (6.48 g, 39.9 mmol) in hydrochloric acid (18%, 120 mL) was cooled to 0 C. A solution of sodium nitrite (3.25 g, 47.2 mmol) in H2O (8.0 mL) was added dropwise. The resulted yellow solution was stirred at 0 C for 1 h. A suspension of CuCl (5.90 g, 59.9 mmol) in H2O (8.0 mL) was added to the above solution slowly. The mixture was stirred at 0 C for 3 h and further stirred at 50 C for 1 h. The precipitate was collected by filtration washed by water, dried in vacuum affording a light yellow solid 6 (4.90 g, 68% yield). 1H NMR (DMSO-d6): delta (ppm) 11.50 (s, 1H, CONHCO), 7.88 (d, 1H, 1.6 Hz), 7.87-7.82 (m, 2H). 13C NMR (DMSO-d6): delta (ppm) 168.23, 167.83, 138.99, 134.57, 134.00, 131.12, 124.64, 122.95.

According to the analysis of related databases, 3676-85-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Song, Xiaoyu; Zhao, Jing; Zhang, Wandong; Chen, Long; Chinese Chemical Letters; (2018); p. 331 – 335;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route 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.

General procedure: To a 25 mL round bottomed flask was added different substituted oxindoles 8 (0.2 mmol, 1.0 equiv.) and bromoethylsulfonium salt 9 (132.99 mg, 0.3 mmol, 1.5 equiv.), DMF (2 mL). The mixture was stirred at room temperature for 5min and Et3N (61.88 mg, 0.6 mmol, 3.0 equiv.) was added into reaction system. The mixture was stirred for 6h at room temperature until the reaction completed, quenched with saturated ammonium chloride solution (5 mL), and was extracted with EtOAc (3¡Á30 mL). The combined organic layer washed with H2O (2¡Á10 mL), dried with anhydrous sodium sulfate. After concentration, product was purified using column chromatography on silica gel with suitable eluent.

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:
Article; Qin, Hui; Miao, Yuanyuan; Zhang, Ke; Xu, Jian; Sun, Haopeng; Liu, Wenyuan; Feng, Feng; Qu, Wei; Tetrahedron; vol. 74; 47; (2018); p. 6809 – 6814;,
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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. 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, A new synthetic method of this compound is introduced below., Computed Properties of C10H9NO3

Sodium hydroxide solution (1N, 20 ml) was added to a solution of methyl 2-oxoindoline-6-carboxylate (2 g, 10.46 mmol, 1.00 equiv) in methanol (20 ml). The resulting solution was stirred for 2 hours at 80 C. The reaction mixture was cooled to 30 C., diluted with 50 ml of H2O and extracted with 2*30 mL of dichloromethane. The aqueous layers were combined and the pH adjusted to 2 with aqueous hydrochloric acid (6 N). The solids were collected by filtration and dried to give the title product 1.28 g (69%) as a brown solid. 1H NMR (400 MHz, CDCl3) delta: 12.86 (s, 1H), 10.50 (s, 1H), 7.55 (m, 1H), 7.32-7.30 (m, 2H), 3.56 (s, 2H).

The synthetic route of 14192-26-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Auspex Pharmaceuticals, Inc.; Rao, Tadimeti; Zhang, Chengzhi; US2015/284327; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1029691-06-2, name is 2-(3-Oxocyclopentyl)isoindoline-1,3-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. Safety of 2-(3-Oxocyclopentyl)isoindoline-1,3-dione

Mix (+/-)-2-(3-oxo-cyclopentyl)-isoindole-1,3-dione (12.7 g, 55.3 mmol) and 4-cyanophenylhydrazine-HCl (8.53 g, 50.3 mmol) in HOAc (200 mL) and 4N HCl dioxane (50 mL). Using mechanical stirring, heat the reaction to 90 C. for 18 h, then add additional 4N HCl dioxane (20 mL). Heat the reaction to 100 C. for 18 h. Dilute the reaction mixture with water (600 mL) and collect a black solid by vacuum filtration. Sonicate the solid with MeOH (200 mL), then collect and dry in a vacuum oven to give 10.94 g (66%) of a gray-brown solid. MS (m/z): 328 (M+1), 326 (M-1).

The synthetic route of 1029691-06-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Gavardinas, Konstantinos; Green, Jonathan Edward; Jadhav, Prabhakar Kondaji; Matthews, Donald Paul; US2010/69404; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 552330-86-6,Some common heterocyclic compound, 552330-86-6, name is 5-Bromoisoindolin-1-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.

Intermediate No.165 *romo-2 -trimethyl-2 -dihvdro-l/y soindol-l-one5-Bromo-2,3-dihydro-lH-isoindol-l-one (150 mg, 0.71 mmol) was dissolved in DMF (3.5 mL) and stirred at ambient temperature. NaH (85 mg, 2.1 mmol, 60% dispersion in oil) was carefully added in two portions, and the resulting mixture was allowed to stir for 15 minutes before Mel (151 mg, 1.06 mmol) was added. The mixture was allowed to stir at ambient temperature for 30 minutes before water (10 mL) was carefully added. The mixture was extracted with EtOAc, and the organic layer was washed with water, brine, dried over anhydrous MgS04, filtered, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-20% EtOAc/hexanes). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound.LRMS (ESI) calc’d for Ci iH12BrNO [M+H]+: 254, Found: 254.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromoisoindolin-1-one, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; BRUBAKER, Jason; DINSMORE, Christopher J.; HOFFMAN, Dawn Marie; JUNG, Joon; LIU, Duan; PETERSON, Scott; SIU, Tony; TORRES, Luis E.; ZHANG, Hongjun; WEI, Zhongyong; SHI, Feng; WO2013/40863; (2013); A1;,
Indoline – Wikipedia,
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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. 4403-36-5, name is 2-(1,3-Dioxoisoindolin-2-yl)ethanesulfonylchloride belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. COA of Formula: C10H8ClNO4S

Triethylamine (50 mul), DMAP (catalytic amount) and 2-(1,3-dioxo-1,3- dihydro-isoindol-2-yl)-ethanesulfonyl chloride (27.4 mg, 0.10 mmol) were added to 0.034 mmol 45. The reaction mixture was stirred at room temperature for 18 hours under an inert atmosphere. The reaction was monitored by TLC (EtOAc/hexane 3/7) (Rf44 = 0.5, Rf45 = 0, Rf268 = 0.4) and LC/MS. After completion of the reaction, the mixture was diluted with EtOAc (20mL) and washed with IN HCI, saturated NaHC03 and brine. The organic phase was dried (MgS04), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (ethylacetate/hexane – 3/7) to afford 2- (1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonic 9- benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5- yl ester 268 (12.2 mg, 50%).

The synthetic route of 4403-36-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GILEAD SCIENCES, INC.; CAI, Zhenhong, R.; CHEN, Xiaowu; FARDIS, Maria; JABRI, Salman, Y.; JIN, Haolun; KIM, Choung, U.; METOBO, Sanuel, E.; MISH, Michael, R.; PASTOR, Richard, M.; WO2005/117904; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem