Category: indolines-derivatives

Adding a certain compound to certain chemical reactions, such as: 222036-66-0, name is 5-Aminoisoindolin-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 222036-66-0, COA of Formula: C8H8N2O

A mixture of 3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (100 mg, 0.26 mmol), 5-aminoisoindolin-1-one (38 mg, 0.26 mmol), 1-methyl-1H-imidazole (84 mg, 1.02 mmol) and EDCI (196 mg, 1.02 mmol) in DMF (3 mL) was stirred for 16 h at room temperature. Ethyl acetate (5 mL) and water (5 mL) were added. The organic layer was separated and the aqueous phase was extracted with ethyl acetate (20 mL). The organic phases were combined and washed with brine (10 mL) then dried over Na2SO4. The residue was concentrated and triturated with MeOH (2 mL) to give 3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(1-oxoisoindolin-5-yl)benzamide (26 mg, 20percent) as a yellow solid. 1H NMR (300 MHz, DMSO): delta 10.68 (s, 1H), 9.97 (s, 1H), 8.61 (s, 1H), 8.52 (s, 1H), 8.44 (s, 1H), 8.24-8.08 (m, 4 h), 7.82-7.64 (m, 4 h), 7.41 (d, 1H, J=8.7 Hz), 7.11 (d, 1H, J=8.4 Hz), 4.39 (s, 2H), 4.02 (s, 3H), 3.76 (s, 3H). LC-MS: [M+H]+, 521.9, tR=1.434 min, HPLC: 96.12percent at 214 nm, 96.79percent at 254 nm, tR=3.673 min.

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; Hoffmann-La Roche Inc.; Hermann, Johannes Cornelius; Kuglstatter, Andreas; Lucas, Matthew C.; Padilla, Fernando; Wanner, Jutta; Zhang, Xiaohu; US2013/109661; (2013); A1;,
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., Application In Synthesis of 5-Nitroindoline-2,3-dione

Example 17 (S)-3,5-Dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)- phenyl)-2-(2-(5-(methylsulfonamido)-2,3-dioxoindolin-1 -yl)acetoxy)ethyl)- pyridine 1 -oxide (Compound 99) Scheme 17 Step 1. Preparation of 5,5-dimethyl-5′-nitrospiro[[1 ,3]dioxane-2,3′- indolin]-2′-one (94) A mixture of 5-nitroindoline-2,3-dione (305 mg, 1 .587 mmol), 2,2-dimethylpropane-1 ,3-diol (165 mg, 1 .587 mmol) and p-toluenesulfonic acid monohydrate (catalytic amount) in cyclohexane (9 ml) was stirred at reflux temperature (removing water by a Dean-Stark apparatus) for 6 hours. The reaction was cooled to room temperature and the solid was recovered by filtration and washed with petroleum ether, affording 5,5-dimethyl-5′-nitrospiro[[1 ,3]dioxane-2,3′-indolin]-2′- one (481 mg). that was used as such in the following step. MS/EST 279.0 [MH]+.

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 611-09-6.

Reference:
Patent; CHIESI FARMACEUTICI S.P.A.; ARMANI, Elisabetta; AMARI, Gabriele; CAPALDI, Carmelida; CARZANIGA, Laura; LA PORTA, Elena; GUALA, Matilde; WO2013/57013; (2013); A2;,
Indoline – Wikipedia,
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. 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal, A new synthetic method of this compound is introduced below., Formula: C11H9NO3

A solution of 7a (30.1 mg, 0.15 mmol, 1.5 eq) and (S)-10 (0.6 mg, 0.001 mmol, 0.01 eq) was stirred atroom temperature in anhydrous THF (2 mL) for 30 min before adding NFSI (31.2 mg, 0.01 mmol,1 eq). The reaction mixture was then stirred at room temperature for 6 h, then pentane was added andthe precipitate was filtered off. The residue was concentrated and then dissolved in MeOH (2 mL),NaBH4 (1 mmol) was added and stirred for 1 h at room temperature. The reaction was quenched with(1M, 2 mL) aqueous solution of KHSO4, (2 mL) water was added and the aqueous layer was extractedwith EtOAc (3 5 mL), the organic layers was collected and dried over MgSO4 and evaporated invacuo. The crude compound was subjected to silica gel column (98%-90% hexane/EtOAc) to give thetitle compound as colourless oil;

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:
Article; Cheerlavancha, Raju; Ahmed, Ahmed; Leung, Yun Cheuk; Lawer, Aggie; Liu, Qing-Quan; Cagnes, Marina; Jang, Hee-Chan; Hu, Xiang-Guo; Hunter, Luke; Beilstein Journal of Organic Chemistry; vol. 13; (2017); p. 2316 – 2325;,
Indoline – Wikipedia,
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. 496-12-8, name is Isoindoline, A new synthetic method of this compound is introduced below., Safety of Isoindoline

methyl 1-(6-chloropyrimidin-4-yl)piperidine-4-carboxylate 15 (500 mg, 1.96mmol), 2,4-difluorophenol (1.02 g, 7.82mmol) and Cs2CO3 (2.56 g, 7.82mmol) were combined in a microwave vial, and NMP (11mL) was added. The resulting solution was heated to 180C with microwave irradiation for 20 min, after which time solids were removed by filtration, and crude residue was purified by RP-HPLC. Fractions containing product were extracted with 3:1 chloroform/IPA. Solvents were dried with MgSO4, filtered and concentrated to give product 16 as a brown, spongy solid (320 mg, 49%). 1H NMR (400MHz, CDCl3) delta 8.27 (s, 1H), 7.20 – 7.14 (m, 1H), 6.97 – 6.88 (m, 2H), 6.05 (s, 1H), 4.27 – 4.24 (m, 2H), 3.17 – 3.10 (m, 2H), 2.70 – 2.63 (m, 1H), 2.06 – 2.02 (m, 2H), 1.82 – 1.73 (m, 2H); 13C NMR (101MHz, CDCl3) delta 179.03, 169.60, 163.87, 161.28, 161.18, 158.82, 158.72, 157.72, 156.01, 155.89, 153.51, 153.38, 136.62, 124.63, 124.54, 111.68, 111.64, 111.45, 111.41, 105.68, 105.46, 105.41, 105.19, 85.88, 43.83, 40.68, 27.46 (multiple Cs coupled to F). LCMS (215nm) RT=0.764 min (>98%); m/z 336.2 [M+H]. Compound 16 (50 mg, 0.15mmol) and isoindoline (0.028mL, 0.22mmol) were dissolved in DMF (2mL), and DIPEA (0.13mL, 0.75mmol) and HATU (85 mg, 0.22mmol) were added. The resulting solution was stirred at r.t. for 1 h, after which time crude residue was purified directly by RP-HPLC. Fractions containing product were basified with sat. NaHCO3, and extracted with 3:1 chloroform/IPA. Organic extracts were filtered through a phase separator and concentrated to give product 17e as a light brown solid (42 mg, 65%). 1H NMR (400MHz, CDCl3) delta 8.26 (s, 1H), 7.32 – 7.27 (m, 4H), 7.20 – 7.14 (m, 1H), 6.96 – 6.87 (m, 2H), 6.09 (s, 1H), 4.93 (s, 2H), 4.82 (s, 2H), 4.48 – 4.41 (m, 2H), 3.10 – 3.03 (m, 2H), 2.83 – 2.75 (m, 1H), 1.93 – 1.88 (m, 4H); 13C NMR (101MHz, CDCl3) delta 173.19, 169.70, 163.99, 161.12, 161.02, 158.67, 158.57, 157.87, 156.02, 155.90, 153.52, 153.39, 136.74, 136.70, 136.62, 136.58, 136.54, 136.01, 128.10, 127.72, 124.64, 124.62, 124.54, 124.52, 123.22, 122.70, 111.55, 111.51, 111.32, 111.29, 105.56, 105.34, 105.29, 105.07, 85.94, 52.51, 52.47, 43.96, 40.47, 27.59 (multiple Cs coupled to F). LCMS (215nm) RT=0.950 min (>98%); m/z 437.2 [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:
Article; Bender, Aaron M.; Weiner, Rebecca L.; Luscombe, Vincent B.; Cho, Hyekyung P.; Niswender, Colleen M.; Engers, Darren W.; Bridges, Thomas M.; Jeffrey Conn; Lindsley, Craig W.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 11; (2017); p. 2479 – 2483;,
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. 897957-06-1, name is 6-Bromo-1-methylindolin-2-one, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 897957-06-1

To I-5.2 (32.0 g, 142 mmol) in anhydrous dioxane (400 mL) is added R11 (54.4 g, 241 mmol) and potassium acetate (41.6 g, 424 mmol). The mixture is purged with Argon, [1,1?-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) as a complex with dichloromethane (11.2 g, 14 mmol) is added and the mixture is heated to 90 C. for 2 h. The reaction mixture is diluted with ethyl acetate and water, the organic layer is washed with water, dried over MgSO4 and concentrated. The residue is purified via flash chromatography (cyclohexane/EA=70:30). Yield 72%, m/z 274 [M+H]+, rt 0.67 min, LC-MS Method V011_S01.

According to the analysis of related databases, 897957-06-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRAUERT, Matthias; GRUNDL, Marc; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; US2014/275159; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 496-12-8, 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. 496-12-8, name is Isoindoline, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 2,3-dihydro-1 H-isoindole (0.3 mL) in dichloromethane (5 mL)Triethylamine (0.7 mL)And the mixture was ice-cooled to 0 C.,2-Bromoacetyl bromide (0.4 mL) was added dropwise, followed by stirring at room temperature for 18 hours.Water was added to the reaction solution, the mixture was extracted with dichloromethane and washed with saturated brine.The organic layer was dried over sodium sulfate and the solvent was distilled off under reduced pressure to obtain a residue.Purification by silica gel column chromatography (hexane-ethyl acetate)2-Bromo-1- (2,3-dihydro-1 H-isoindol-2-yl)Ethan-1-one281 mg (yield 47%) was obtained.

The chemical industry reduces the impact on the environment during synthesis Isoindoline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; NATIONAL CENTER FOR GERIATRICS AND GERONTOLOGY; YANAGISAWA, KATSUHIKO; KAWAI, AKIYOSHI; (139 pag.)JP2017/171619; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 2436-29-5, 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. 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Step 1.A solution of 9-((3aR,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydrofuro[3,4- d][l,3]dioxol-4-yl)-9H-purin-6-amine (400 mg, 1.3 mmol) and 3-(l,3-dioxoisoindolin-2- yl)propanal (293 mg, crude 1.44mmol) in DCE (8 mL) were stirred at rt for 0.5 h, then NaBH(OAc)3 (416 mg, 1.96 mmol) was added. The reaction was stirred at rt overnight. The reaction was quenched with aqu. sat. NaHC03 (2 mL), extracted with DCM (10 mLx3), washed with brine (10 mL), dried and concentrated. The residue was purified by prep-TLC (DCM : MeOH = 10 : 1) to the title compound (350 mg, Yield 43%). NMR (500 MHz, MeOD): delta 8.28 (s, 1H), 8.21 (s, 1H), 7.83-7.76 (m, 4H), 6.14(d, J = 3.5 Hz, 1H), 5.46-5.44 (m, 1H ), 5.01-4.99 (m, 1H), 4.32 (br s, 1H), 3.65-3.62 (m, 2H), 2.85-2.83 (m, 2H), 2.57-2.53 (m, 2H), 1.79-1.76 (m, 2H), 1.58 (s, 3H), 1.37 (s, 3H) ppm; ESI-MS (m/z): 494.2[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, 3-(1,3-Dioxoisoindolin-2-yl)propanal, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EPIZYME, INC.; CHESWORTH, Richard; KUNTZ, Kevin, Wayne; OLHAVA, Edward, James; PATANE, Michael, A.; WO2012/82436; (2012); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. Computed Properties of C22H19N3O6

This example relates to preparation of the compound (5S)-4-{4-[5- (aminomethyl)-2-oxo-1 ,3-oxazolidine-3-yl]phenyl}morpholine-3-one nitrate, step c) of the process. 17.0 kg of the compound (IV) obtained in example 2, 170 kg of ethanol and 20.4 kg of methylamine in aqueous solution at 40% by weight, are loaded into a reactor. The temperature of the reactant system is then brought to about 60 C and maintained at this value for 3 hours. At the end of the reaction, the mass obtained is distilled under vacuum until a dense residue is obtained; 170 kg of ethanol and 34.0 kg of water are added to the residue. 4.47 kg of an aqueous solution at 65% by weight of nitric acid, are slowly added to the mixture thus obtained, maintained at a temperature of about 30 C. At the end of the addition of the acid, the precipitate is filtered and washed with 25.5 kg of ethanol and lastly oven-dried. 1 1 .0 kg of the desired compound (V) are obtained, with a reaction yield equal to 76.9%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 446292-08-6, its application will become more common.

Reference:
Patent; ERREGIERRE S.P.A.; FERRARI, Massimo; GHEZZI, Emanuele; GHEZZI, Marcello; WO2015/198259; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 13861-75-1, These common heterocyclic compound, 13861-75-1, name is Spiro[cyclopropane-1,3′-indolin]-2′-one, 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.

[0272] To a cooled (0C) solution of spiro[cyclopropane-l,3′-indolin]-2′-one (prepared according to methods described in J. Med. Chem. 1987, 824-829; J. Med. Chem. 1992, 163-172; U.S. Patent 5,182,397) (1.0 g, 6.21 mmol) in NN-dimethylformamide (5 mL), was added sodium hydride (0.149 g, 6.21 mmol), followed by addition of l-bromo-3-chloropropane (0.733 mL, 7.45 mmol, d = 1.6). After stirring at room temperature for 18 hours, the reaction mixture was diluted with ethyl acetate (100 mL), washed with dilute citric acid, water and brine. The organic phase was dried over MgS04, filtered and isolated by Biotage flash chromatography (10-40% ethyl acetate/hexanes) to obtain the title compound (1.1 g, 68%); ¾ NMR (DMSO-i 6): delta 1.50-1.54 (m, 2H), 1.56-1.61 (m, 2H), 2.01- 2.15 (m, 2H), 3.67 (t, 2H, J= 6.4 Hz), 3.86 (t, 2H, J= 6.8 Hz), 6.97-7.03 (m, 2H), 7.11 (d, 1H, J= 8 Hz), 7.22-7.27 (m, 1H); MS for Ci3H14ClNOm/z 236.04 (M+H)+.

The synthetic route of 13861-75-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ALTOS THERAPEUTICS, LLC; LUEHR, Gary, W.; SUNDARAM, Arathi; JAISHANKAR, Priyadarshini; PAYNE, Philip, W.; DRUZGALA, Pascal; WO2011/160084; (2011); 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 1127-59-9 as follows. Recommanded Product: 1127-59-9

General procedure: A solution of isatin derivatives 1 (0.4 mmol), 3-methyl-4-nitro-5-alkenyl-isoxazoles 2 (0.6 mmol) and proline or thioproline or sarcosine (0.8 mmol) in 10.0 mL of CH3CN at 80 °C for 24 h. After completion of the reaction, as indicated by TLC, the reaction mixture was directly subjected to flash column chromatography on silica gel (petroleum ether/EtOAc5:1-3:1) to furnish the corresponding products 3-5.

According to the analysis of related databases, 1127-59-9, the application of this compound in the production field has become more and more popular.

Reference:
Article; Liu, Xiong-Wei; Yao, Zhen; Yang, Jun; Chen, Zhi-Yong; Liu, Xiong-Li; Zhao, Zhi; Lu, Yi; Zhou, Ying; Cao, Yu; Tetrahedron; vol. 72; 10; (2016); p. 1364 – 1374;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem