Category: indolines-derivatives

18711-13-2, name is 4,7-Dichloroindoline-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. Quality Control of 4,7-Dichloroindoline-2,3-dione

4,7-Dichloro-3-hydroxy-3-(2-oxo-2-(4-(pyrrolidin-l-yl)phenyl)ethyl)indolin-2-one (EXAMPLE 10): To 4,7-dichloroindoline-2,3-dione (A) (12.5 g, 0.06 mol) in 800 mL of methanol were added l-(4-(pyrrolidin-l-yl)phenyl)ethanone (B) (45 g, 0.24 mol) and 0.5 mL of diethylamine (2). The reaction was stirred at rt for 24 hours. The solvent was removed and the residue was purified with flash chromatography (0-5% Methanol/CLLCn) to get 13.5 g of brown solid. It was purified again with flash chromatography using ethyl acetate/hexane to give 11.5 g of an off white solid. Repeating the reaction at the same scale to give another 11.5 g of product. Two batches of product were combined and recrystallized from methanol to get 20.5 g as an off white solid. 4,7-Dichloro-3-hydroxy-3-(2-oxo-2-(4-(pyrrolidin-l- yl)phenyl)ethyl)indolin-2-one (EXAMPLE 10): off-white solid; 1H NMR (DMSO-d6, 400 MHz) delta 1.96 (m, 4H), 3.30 (m, 4H), 3.65 (d, 1H, J=16 Hz), 4.29(d, 1H, J=16Hz), 6.34 (s, 1H), 6.53(d, 2H, J=8Hz), 6.88(d, 1H, J=8Hz), 7.28 (d, 1H, J=8Hz), 7.72 (d, 2H, J=8Hz), 10.97(s, 1H). Chiral separation was performed on under the following conditions. Preparatory method utilized the following:a RegisCell column L: 250 mm, IS: 50 mm, particle size: 5 mum; mobile phase: methanol/CO2, ratio: 35/65, detection wavelength: 254 nm, flow rate: 325 g/min, co-solvent flow rate 113.75 ml/min. Dissolved 19.72 g in 1000 ml of methanol, for a concentration of 0.020 g/ml. The injection volume was 25.00 ml for a total amount 0.500 g/injection. Yield was (+): 9.73 g, with optical rotation +247 at 20 C and (-): 9.26 g.

The synthetic route of 18711-13-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TOKALAS, INC.; VERNIER, Jean-michael; (82 pag.)WO2016/57698; (2016); A1;,
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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. 20870-79-5, name is 5-Nitroindolin-2-one, A new synthetic method of this compound is introduced below., category: indolines-derivatives

Example 159b 5-amino 1,3-dihydro-indol-2-one A mixture of 1.5 g (8.4 mmol) of 5-nitro-1,3-dihydro-indol-2-one, 150 mg of Pd/C 10%, and 50 ml MeOH in 100 ml of EtOAc was placed on Parr hydrogenator and charged with 45 psi of Hydrogen gas. The mixture was shaken for 2 hrs. The mixture was filtered and the solvent was removed in vacuo to yield 5-amino 1,3-dihydro-indol-2-one (1.22 g, 98%): 1H NMR (DMSO-d6): delta3.27 (s, 2H), 4.6 (s, 2H), 6.34 (dd, J1=2 Hz, J2=8.1 Hz, 1H), 6.45 (m, 2H), 9.88 (s, 1 H). APCI-MS: m/z 147 (m-H)-.

The synthetic route of 20870-79-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Glaxo Wellcome Inc.; US6268391; (2001); B1;,
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Application of 35197-64-9, 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. 35197-64-9, name is 2-Bromo-4-(1,3-dioxoisoindolin-2-yl)butanoic acid belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: In this work, previously reported N-benzyl-2-bromo-4-(1,3-dioxoisoindolin-2-yl)butanamide derivatives (25a-e) [44] were obtained by activating the carboxylic acid group of 24 (1 eqv) by using n-propanephosphonic acid anhydride (T3P, 50% in EtOAc, 1 eqv). The reaction was carried out under argon atmosphere for 2hat 0C in dry methylene chloride. Then, distilled triethylamine (1.2 eqv) and the appropriate N-benzylamine (1.1 eqv) were added to the reaction mixture [57]. The reaction was continued at room temperature for 12h. The products were purified by column chromatography over silica gel (DCM/acetone=9:1) to yield 25a-e as a white solid.

The synthetic route of 2-Bromo-4-(1,3-dioxoisoindolin-2-yl)butanoic acid has been constantly updated, and we look forward to future research findings.

Reference:
Article; ?mudzki, Pawe?; Fija?kowski, ?ukasz; Furga?a, Anna; Gryz?o, Beata; Hoefner, Georg C.; Kulig, Katarzyna; Malawska, Barbara; Malawska, Katarzyna; Nowaczyk, Alicja; Podkowa, Adrian; Rapacz, Anna; Sa?at, Kinga; Wanner, Klaus T.; Zar?ba, Paula; European Journal of Medicinal Chemistry; vol. 188; (2020);,
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Electric Literature of 169037-23-4, 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 169037-23-4 as follows.

General procedure: General method: The Schiff bases were obtained by adding an ethanolic solution of the hydrazinyl component to the solution of the keto component in equimolar amounts, refluxing the mixture in the presence of catalytic amounts of acid. If not indicated otherwise, purification was carried out by recrystallization. Carbazides were prepared by adding an equimolar amount of hydrazine to the methanolic solution of the respective isothiocyanate [53]. For the picolinylidene derivatives with ethyl group in 5-position of the pyridine moiety (2e, 2k), 5-Ethylpicolinaldehyde was prepared from 5-ethyl-2-methyl-pyridine as reported previously [13,115]. The reaction of 5-trifluoromethoxyisatin (50mg, 0.22mmol) with N-(4-methoxyphenyl)hydrazinecarbothioamide C-1 (43mg, 0.22mmol) in ethanolic solution under HCl-catalysis resulted in a yellow fluffy precipitate, which was identified as the product in 70% yield (65.7mg, 0.16mmol). 1H NMR (500MHz, DMSO-d6): delta=12.60 (s, 1H), 11.36 (s, 1H), 10.78 (s, 1H), 7.78 (s, 1H), 7.49-7.41 (m, 2H), 7.41-7.31 (m, 1H), 7.02 (d, 1H, 3J(H,H)=5.0Hz), 7.01-6.95 (m, 2H), 3.78 (s, 3H). 13C NMR (126MHz, DMSO-d6): delta=176.6, 162.7, 157.5, 143.5, 141.2, 131.1, 130.9, 127.3 (2C), 124.0, 121.5, 120.7 (d {121.19, 119.15}, 1J(C,F)=255.7Hz), 114.4 (2C), 113.6, 112.1, 55.3. Anal. Calcd. for C17H13N4SO3F3: C: 49.76; H: 3.19; N: 13.65. Found: C: 49.61; H: 3.477; N: 13.53

According to the analysis of related databases, 169037-23-4, the application of this compound in the production field has become more and more popular.

Reference:
Article; Pape, Veronika F.S.; Toth, Szilard; Fueredi, Andras; Szebenyi, Kornelia; Lovrics, Anna; Szabo, Pal; Wiese, Michael; Szakacs, Gergely; European Journal of Medicinal Chemistry; vol. 117; (2016); p. 335 – 354;,
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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. 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. Quality Control of Indolin-2-one

EXAMPLE 483A 5-bromo-1,3-dihydro-2H-indol-2-one A suspension of 1,3-dihydro-indol-2-one (1.3 g, 9.76 mmol) in acetonitrile (20 mL) at -5 C. was treated with N-bromosuccinimide, warmed to room temperature, stirred overnight and filtered to give 1.8 g (87% yield) of the desired product. MS (ESI(+)) m/e 209.9, 211.9 (M-H)-.

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

Reference:
Patent; Betschmann, Patrick; Burchat, Andrew F.; Calderwood, David J.; Curtin, Michael L.; Davidsen, Steven K.; Davis, Heather M.; Frey, Robin R.; Heyman, Howard R.; Hirst, Gavin C.; Hrnciar, Peter; Michaelides, Michael R.; Muckey, Melanie A.; Rafferty, Paul; Wada, Carol K.; US2005/26944; (2005); A1;,
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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. 110568-64-4, name is 6-Nitroisoindolin-1-one, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 6-Nitroisoindolin-1-one

Step 4: Synthesis of 5-Amino-2,3-dihydro-isoindol-1-one To a suspension of Fe (1.1 g, 19.6 mmole), NH4Cl (1.5 g, 28 mmole) in a mixture of ethanol/water (30 ml/7 ml) at 80° C. was added a mixture of 5-Nitro-2,3-dihydro-isoindol-1-one (1 g, 5.6 mmole) in 10 ml ethanol. The reaction mixture was stirred at 80° C. for 2 hours. Mixture was cooled down, filtered off, solid was washed with 50 ml ethanol. The filtrate was concentrated, taken into 50 ml ethylacetate, washed with 20 ml water. Organic layer was dried over Na2SO4, filtered and concentrated to give about 900 mg crude. Trituration with methyl t-butylether gave 400 mg pure product, 48percent yield. A 18 ml vial was loaded with a mixture of 30percent H2O2 (1 ml), 3N NaOH (3 ml) and MeOH (2.5 ml). To this mixture 5-Amino-pyridine-2-carbonitrile (450 mg, 3.78 mmole) was added at room temperature. Reaction mixture was stirred at rt for 45 minutes, TLC showed the starting material to be consumed. The mixture was diluted with water and filtered; the solid was washed with water and dried to give 480 mg product, 92percent yield.

According to the analysis of related databases, 110568-64-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Nivalis Therapeutics, Inc.; Wasley, Jan; Rosenthal, Gary J.; Sun, Xicheng; Strong, Sarah; Qiu, Jian; US9138427; (2015); B2;,
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Reference of 16800-68-3, 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. 16800-68-3, name is 1-Acetylindolin-3-one, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: In an oven dried round-bottomed flask, a solution of the squaramide catalyst I (2 mol%) and 1-acetylindolin-3-one 1 (0.4 mmol) in CH2Cl2(1.0 mL) was stirred at r.t. After 5 min, the o-formyl-(E)-beta-nitrostyrene2 (0.48 mmol) was added and the stirring was continued until the complete consumption of the reactants was observed by TLC.Then the crude mixture was purified by flash chromatography on silicagel using a gradient of n-hexane-EtOAc (9:1 to 1:1) to afford the desired product 3.

The chemical industry reduces the impact on the environment during synthesis 1-Acetylindolin-3-one. I believe this compound will play a more active role in future production and life.

Reference:
Article; Mahajan, Suruchi; Chauhan, Pankaj; Loh, Charles C. J.; Uzungelis, Server; Raabe, Gerhard; Enders, Dieter; Synthesis; vol. 47; 7; (2015); p. 1024 – 1031;,
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Reference of 18711-13-2,Some common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, molecular formula is C8H3Cl2NO2, 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 4,7-dichloroisatin (0.68 mmol, 1.0 eq) in DMF (4 mL) was added K2CO3 (0.68 mmol, 1.0 eq) at room temperature, the mixture was stirred for about 30 min, and then the propargyl bromide (0.75 mmol, 1.1 eq) was added dropwise. The mixture was stirred overnight at room temperature. Upon completion, EtOAc and H2O were added. The aqueous layer was extracted with EtOAc for several times; the combined organic layers were washed with H2O for several times to remove the DMF, and then washed with brine, dried over MgSO4 and evaporated to give the products. Compound 2, saffron solid, yield: 76%, m. p.: 151.8-153.3 C, Rf = 0.52 (petroleum ether/ethyl acetate 2/1). 1H NMR (400 MHz, CDCl3) delta 7.51 (d, J = 8.7 Hz, 1H), 7.10 (d, J = 8.7 Hz, 1H), 4.94 (d, J = 2.4 Hz, 2H), 2.34 (t, J = 2.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) delta 178.68, 157.00, 146.19, 140.48, 133.05, 126.79, 117.16, 116.11, 77.22, 73.27, 31.94.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4,7-Dichloroindoline-2,3-dione, its application will become more common.

Reference:
Article; Yu, Bin; Wang, Sai-Qi; Qi, Ping-Ping; Yang, Dong-Xiao; Tang, Kai; Liu, Hong-Min; European Journal of Medicinal Chemistry; vol. 124; (2016); p. 350 – 360;,
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These common heterocyclic compound, 20780-72-7, name is 4-Bromoisatin, 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. Computed Properties of C8H4BrNO2

4-bromoisatin 1.0g (4.4mmol), methyl acrylate 0.46g (5.3mmol), PdCl2(PPh3)2 0.15g (0.22mmol), K3PO4 1.6g (6.2mmol). Place into microwave reaction flask. Add 5 ml DMF. Place under argon protection. In the microwave reactor 145 °C reaction 30min. TLC detection after the reaction is complete, the reaction solution with 100 ml saturated salt water washing 3 times, dichloromethane is used for extraction, the combined organic phase, anhydrous sodium sulfate drying, developing agent for petroleum ether: ethyl acetate=5:1 – 1: 1,200 – 300 mesh silica gel column chromatography purification, be 4 – acrylic acid methyl ester indole dione 0.65g, yield 64percent.

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

Reference:
Patent; Tianjin Kunjian Bio-pharmaceutical Co., Ltd.; Yu Peng; Han Kailin; Mao Huihua; Qiu Dongxu; (8 pag.)CN104387312; (2017); B;,
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Some common heterocyclic compound, 825-70-7, name is 5-Fluoro-2-methylindoline, molecular formula is C9H10FN, 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: C9H10FN

Under argon atmosphere conditions, add 0.0151g (0.10mmol) of 5-fluoro-2-methylindolinoline (1d), 0.0013g (0.002mmol) of acid eosinY, 0.150g of Antarctic lipase CAL- A, 0.0146 g (0.10 mmol) of n-octyl mercaptan, 0.104 g (0.50 mmol) of allyl-3-methoxyphenyl carbonate (2b), methyl tert-butyl ether (TBME) 2.0 mL;The reaction was stirred at 45 C for 6 hours under a 6w white light. After the reaction, the insoluble enzyme was removed by suction filtration, the solvent was distilled off under reduced pressure, and the solvent was separated by column chromatography. The eluent: (V) petroleum ether / (V) Ethyl acetate = 30/1. 0.0190 g of a yellow liquid product (3db) was obtained with a product yield of 81%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 825-70-7, its application will become more common.

Reference:
Patent; Central China Normal University; Zhou Shaolin; Shi Weimin; (16 pag.)CN110437123; (2019); A;,
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