Category: 99365-40-9

99365-40-9, The chemical industry reduces the impact on the environment during synthesis 99365-40-9, name is 6-Bromoindolin-2-one, I believe this compound will play a more active role in future production and life.

6-bromoindolin-2-one (0.424 g; 2 mmol), potassium acetate (0.687 g; 7.0 mmol) and bis[pinacolato]diborane (0.762 g; 3.0 mmol) were placed in a 20 mL microwave vial, dissolved in dry DMF (13 mL) and the flask was purged with nitrogen. The catalyst [1 ,1 ‘- Bis(diphenylphosphino)ferrocene]palladium(ll) chloride, complex with dichloromethane (0.169 g; 0.20 mmol) was added, the flask was again purged with argon, sealed and the reaction was heated at 950C for 18 h. The reaction mixture was diluted with water and the suspension was extracted twice with ethyl acetate. The combined organics were washed with brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (10 – 80 %) in heptane furnished 0.390 g (40 %) of the title compound.ESI/APCI(+): 260 (M+H);1H NMR (DMSO-d6) delta 10.40 (s, 1 H), 7.27 (dd, J= 7,3, 0,8 Hz, 1 H), 7.21 (m, 1 H), 7.07 (s, 1 H), 3.50 (s, 2 H), 1.28 (s, 12 H).

The chemical industry reduces the impact on the environment during synthesis 6-Bromoindolin-2-one. I believe this compound will play a more active role in future production and life.

Reference:
Patent; KATHOLIEKE UNIVERSITEIT LEUVEN; CHALTIN, Patrick; DEBYSER, Zeger; DE MAEYER, Marc; MARCHAND, Arnaud; MARCHAND, Damien; SMETS, Wim; VOET, Arnout; CHRIST, Frauke; WO2011/15641; (2011); A1;,
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A common compound: 99365-40-9, name is 6-Bromoindolin-2-one, belongs to indolines-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 99365-40-9

To a suspension of potassium tert-butylate (12.8 g) in dry THF (80 ml) was added portion wise at 0 C 6-bromoindolin-2-one (5.0 g,) followed by copper (I) bromide-dimethylsulfide complex(470 mg). Mel (6.82 g) was added drop wise within 45 mm keeping the internal temperature below 8 C, the mixture was warmed to 22 C and stirring was continued for 16 hours. The mixture was quenched at 0 C with saturated aqueous ammonium chloride solution and diluted with TBME and water. The organic layer was dried, evaporated and the residue purified by flash chromatography (silica gel, EtOAc/ n-heptane, 1:1) to give the title compound (5.17 g) as abrown solid (5.17 g, 9 1%). MS (mlz): 240.4/ 242.4 [(M+H)?i.

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, 99365-40-9, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; HILPERT, Hans; KOLCZEWSKI, Sabine; HUMM, Roland; STOLL, Theodor; MUSER, Thorsten; PLANCHER, Jean-Marc; GAUFRETEAU, Delphine; (142 pag.)WO2015/197567; (2015); A1;,
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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. 99365-40-9 name is 6-Bromoindolin-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. 99365-40-9

Commercially available 6-bromoxindole (656 mg), zinc cyanide (288 mg) and tetrakis triphenylphosphine palladium(0) (175 mg) were suspended in dry N,N-dimethylformamide (6 mL). The resulting mixture was degassed by three pump/vent cycles with argon and then placed in a preheated oil bath (80 C.). After stirring at this temperature for 15 h the mixture was cooled to room temperature, diluted with water (60 mL) and extracted with ethyl acetate (3¡Á60 mL). The combined organic layers were washed with water (2¡Á60 mL), dried (MgSO4), filtered and concentrated. The remaining residue was purified by flash chromatography (silica, dichloromethane/methanol) to afford the title compound (385 mg; 81%). [MH]+=159.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromoindolin-2-one, and friends who are interested can also refer to it.

Reference:
Patent; Alantos Pharmaceuticals, Inc.,; US2006/173183; (2006); A1;,
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99365-40-9, A common compound: 99365-40-9, name is 6-Bromoindolin-2-one, belongs to indolines-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

General procedure: To the phenstatin-3-aldehyde/isocombretastatin-3-aldehyde(16a-b) (0.303 mmol/0.304 mmol) prepared in the above stepwas added corresponding substituted oxindoles (17a-h)(0.303 mmol) and catalytic amount of piperidine (1.0 ml) in ethanol.Heated the reaction mixture to reflux for 4 h at 85 C. The solidcompounds obtained in the reaction vessel were filtered and washed with ethanol for 4-5 times. After complete air drying thefinal compounds phenstatin/isocombretastatin-oxindole analogs(5a-h and 6a-h) were obtained as pure solids (yield 71-90%).

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-Bromoindolin-2-one, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Kumar, G. Bharath; Nayak, V. Lakshma; Sayeed, Ibrahim Bin; Reddy, Vangala Santhosh; Shaik, Anver Basha; Mahesh, Rasala; Baig, Mirza Feroz; Shareef, Mohd Adil; Ravikumar; Kamal, Ahmed; Bioorganic and Medicinal Chemistry; vol. 24; 8; (2016); p. 1729 – 1740;,
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Adding some certain compound to certain chemical reactions, such as: 99365-40-9, name is 6-Bromoindolin-2-one, 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 99365-40-9. 99365-40-9

Example 20: 3-Amino-6- (4-12-hydroxy-2- [5- (2-oxo-2, 3-dihydro-lH-indol-6-yl)- pyridin-2-yl]-ethylamino}-piperidin-1-yl)-4-trifluoromethyl-thieno [2, 3-b] pyridine-2- carboxylic acid amide An N2-purged suspension of 3-Amino-6-{4-[2-(5-bromo-pyridin-2-yl)-2-hydroxy- ethylamino]-piperidin-1-yl}-4-trifluoromethyl-thieno [2, 3-b] pyridine-2-carboxylic acid amide (150 mg, 0.268 mmol), bis (pinacolato) diboron (153 mg, 0.590 mmol), [1,1′- bis (diphenylphosphino) ferrocene] dichloropalladium (II)-CH2Cl2 complex (33 mg, 0.040 mmol), and potassium acetate (133 mg, 1.34 mmol) in dry DMF (4 ml) was heated at 80 C for 2.5 h. The crude reaction mixture was then added directly via syringe to a stirring, N2- purged suspension of 6-bromo-2-oxindole (65 mg, 0.295 mmol), tetrakis (triphenylphosphine) palladium (0) (47 mg, 0.040 mmol), and potassium carbonate (74 mg, 0.536 mmol) in dry DMF (6 ml) and water (2 ml) at rt. The sealed mixture was heated to 85 C for 4 h. The crude reaction was applied direcly to a Si02 column and purified (0-25% MeOH/CH2Cl2 with NH4OH). Fractions containing desired product were pooled and concentrated. The yellow residue was dissolved in 2 ml DMF and applied to a 2 mm prep plate (Merck) eluting with 10% MeOH/CH2Cl2 with 1% NH40H. The yellow product crystallized at the origin and the impurities were removed by being carried up the plate. The recovered yellow residue was dissolved in 1 ml DMF, 2 ml MeOH, 5 ml EtOAc, and 5 ml CH2C12 and crystallized by the addition of 30 ml hexanes to give 20.5 mg, 11.9% of 3-Amino-6- (4-f2-hydroxy-2- [5- (2-oxo-2, 3-dihydro-lH-indol-6-yl)-pyridin-2-yl]- ethylamino}-piperidin-l-yl)-4-trifluoromethyl-thieno [2, 3-b] pyridine-2-carboxylic acid amide product. ES+ 612. 4 m/z (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 6-Bromoindolin-2-one.

Reference:
Patent; BOEHRINGER INGELHEIM PHARMACEUTICALS, INC.; WO2005/56562; (2005); A1;,
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99365-40-9, These common heterocyclic compound, 99365-40-9, name is 6-Bromoindolin-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.

a) 6-(4,4,5,5-Tetramethyl-[1 ,3,2]dioxaborolan-2- l)-1 ,3-dihydro-indol-2-one6-Bromo-1 ,3-dihydro-2H-indol-2-one (150 mg, 0.71 mmol), bis(pinacolato)diboron (233 mg, 0.92 mmol), KOAc (104 mg, 1.07 mmol) and Pd(dppf)CI2 (29 mg) in anhydrous DMF (3 mL) were heated under N2 at 90C for 16 h. The mixture was diluted with EtOAc (40 mL) and washed with water (30 mL) then brine (30 mL). The organic layer was dried (Na2S04) and concentrated in vacuo. Purification by column chromatography (MeOH-DCM gradient) gave a yellow solid (72 mg, 39%); 1H NMR (400 MHz, DMSO-d6) delta 10.38 (s, 1 H), 7.27 (dd, J=7.3, 0.9 Hz, 1 H), 7.23 (d, J=7.3 Hz, 1 H), 7.07 (s, 1 H), 3.49 (s, 2H), 1.29 (s, 12H); m/z (ES+APCI)+: 260 [M+H]+.

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 99365-40-9.

Reference:
Patent; MEDICAL RESEARCH COUNCIL TECHNOLOGY; OSBORNE, Simon; CHAPMAN, Timothy; LARGE, Jonathan; BOULOC, Nathalie; WALLACE, Claire; WO2011/101640; (2011); 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. 99365-40-9, name is 6-Bromoindolin-2-one, A new synthetic method of this compound is introduced below., 99365-40-9

Sodium hydride (4.53 g, 94.3 mmol, Eq: 4) and dry tetrahydrofuran (20 ml) were mixed under argon. A suspension of 6-bromoindolin-2-one (5 g, 23.6 mmol, Eq: 1.00) in dry tetrahydrofuran (50 ml) was added in portions. The mixture was stirred at room temperature for 20 min. Then iodomethane (13.4 g, 5.87 ml, 94.3 mmol, Eq: 4) was added dropwise at 23-26 C. The light brown suspension was stirred at room temperature overnight. The reaction mixture was carefully quenched with 10 ml of saturated ammonium chloride. The mixture was diluted with 200 ml of ethyl acetate, 100 ml of water and 50 ml of saturated sodium bicarbonate. The mixture was extracted with 100 ml of ethyl acetate (2x) and the organic layers were washed with 50 ml of saturated sodium bicarbonate. The combined organic layers were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the desired product a white solid (4.16g, 69 %). MS (m/z) = 254.4/256.4 [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:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; GAUFRETEAU, Delphine; KOLCZEWSKI, Sabine; PLANCHER, Jean-Marc; STOLL, Theodor; (99 pag.)WO2017/76842; (2017); A1;,
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99365-40-9, Adding a certain compound to certain chemical reactions, such as: 99365-40-9, name is 6-Bromoindolin-2-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 99365-40-9.

a) 6-Bromo-3,3-dimethyl-indolin-2-one To a suspension of potassium tert-butylate (12.8 g, 114 mmol) in dry THF (80 ml) at 0C under an argon atmosphere was added portionwise 6-bromoindolin-2-one (5.0 g, 22.9 mmol) followed by copper(I) bromide-dimethylsulfide complex (470 mg, 2.29 mmol). Mel (6.82 g, 3.00 ml, 48.0 mmol) was added dropwise within 45 minutes, keeping internal temperature below 8 C. Thereaction mixture was warmed to room temperature and kept at this temperature for 16 hours. The reaction mixture was cooled to 0 C again and saturated aqueous ammonium chloride solution was cautiously added. The mixture was diluted with tert-butyl methyl ether and water. The aqueous phase was extracted with tert-butyl methyl ether, the combined organic phases were dried over sodium sulfate, the solvent was evaporated and the residue was purified by silica gelchromatography using ethyl acetate heptane as eluent. The title compound was obtained as light yellow solid (5.17 g).MS ESI (mz): 240.0 242.1 [(M+H)i.1H NMR (CDC13, 400 MHz): (ppm) = 8.12 (m, 1H), 7.20-7.16 (m, 1H), 7.09-7.08 (m, 1H),7.06-7.04 (m, 1H), 1.39 (s, 6H).

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-Bromoindolin-2-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BRUNNER, Daniela; HILPERT, Hans; KOLCZEWSKI, Sabine; LIMBERG, Anja; MALBERG, Jessica; PRINSSEN, Eric; RIEMER, Claus; SHANKAR, Bavani G.; STOLL, Theodor; WO2014/202493; (2014); A1;,
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99365-40-9, 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 99365-40-9 as follows.

n-Butyl lithium (2.5 M in hexanes, 3.8 mL, 9.5 mmol) was added dropwise over 30 minutes to a stirred suspension of 6-bromoindolin-2-one (preparation 1, 1.00 g, 4.7 mmol) and N,N,N’,N’-tetramethylethylenediamine (1.42 mL, 9.4 mmol) in tetrahydrofuran (20 mL) at – 78 C. The mixture was stirred for 1 hour, then 1,4-diiodobutane (3.11 mL, 23.6 mmol) was added dropwise over 5 minutes. The mixture was warmed to -20 C over a 1 hour period, was stirred for a further hour at this temperature and was then warmed to room temperature. After 3 hours stirring at room temperature, saturated aqueous ammonium chloride solution was added to the reaction and the mixture was extracted with ethyl acetate. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. Purification of the residue by flash chromatography (10:1 hexanes/ethyl acetate) gave the title compound (0.57 g, 45%) as a pale pink solid. LRMS (m/z): 266/268 (M+1)+. 1H-NMR delta (CDCl3): 1.81-2.20 (m, 8H), 7.02-7.06 (m, 2H), 7.14-7.18 (m, 1H), 7.83 (brs, 1H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 99365-40-9, and friends who are interested can also refer to it.

Reference:
Patent; Laboratorios Almirall, S.A.; EP2108641; (2009); A1;,
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99365-40-9, 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. 99365-40-9, name is 6-Bromoindolin-2-one, This compound has unique chemical properties. The synthetic route is as follows.

Four microwave vials were loaded as follows: 6-bromoindolin-2-one(500 mg, 2.36 mmol), bis(pinacolato)diboron (898 mg, 3.54 mmol),potassium acetate (694 mg, 7.07 mmol) and Pd(dppf)C12CH2C12 (96.0mg, 0.118 mmol) were dissolved in DME (17 mL). The reaction was heated at 80 C overnight. The content of the four vials was then combined, concentrated and purified bycolumn chromatography (CyHex/EtOAc) to afford the title compound as a white solid (2.27 g, 75%, purity 80%). IH NMR (500 MHz, CDCI3) ppm = 8.57 (bs, IH), 7.48 (d, J7.3, IH), 7.31 (5, 1H), 7.23 (d, J=7.3, IH), 3.55 (s, 2H), 1.33 (s, 12H); LC – MS (ESI, mlz) Rt = 2.75 mm – 260 (M+H) (H PLC method E).

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; MERCK PATENT GMBH; CANCER RESEARCH TECHNOLOGY LIMITED; SCHIEMANN, Kai; STIEBER, Frank; CALDERINI, Michel; BLAGG, Julian; MALLINGER, Aurelie; WAALBOER, Dennis; RINK, Christian; CRUMPLER, Simon Ross; (127 pag.)WO2015/144290; (2015); A1;,
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