Month: January 2021

Some common heterocyclic compound, 6326-79-0, name is 6-Bromoisatin, molecular formula is C8H4BrNO2, 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: C8H4BrNO2

The mixture of starting material (6.5 g, 28.7 mmol), malonic acid (3.3 g, 31.7 mmol), HOAc (60 ml), NaOAc (2.95 g, 36 mmol) were stirred at RT. After 6-7 hrs, NaOAc (2.95 g, 36 mmol) was added additional, then refluxed overnight. After cooling, the mixture was filtered and the filtrate was washed with water and ethyl acetate, then dried under reduced pressure. 5 g thin brown solid was collected (yield=65.4%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6326-79-0, its application will become more common.

Reference:
Patent; CanBas Co., Ltd.; US2008/275057; (2008); A1;,
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Application of 201940-08-1,Some common heterocyclic compound, 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, molecular formula is C13H16BrNO2, 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.

Step 2: tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate A solution of tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (0.80 mmol), bis(pinacolato)diboron (0.96 mmol) and potassium acetate (2.5 mmol) in DMF (4 mL) was degassed. To this solution was added PdCl2dppf (1:1 complex with DCM, 0.04 mmol). The reaction mixture was heated at 85 C. for 4 hr and then allowed to cool to rt and diluted with EtOAc. The solution was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (10-30% EtOAc in hexane) to give tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate (0.57 mmol, 72%) as a white solid. LCMS: (FA) ES+346.

The synthetic route of 201940-08-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Millennium Pharmaceuticals, Inc.; US2008/171754; (2008); A1;,
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Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-dione, 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 17564-64-6, COA of Formula: C9H6ClNO2

A solution of benzyl (2S,5S)-2,5-dimethyl-4-oxo-piperidine-1-carboxylate (46.3 g, 177.2 mmol) in THF (280 mL) was cooled to -78 C before LiHMDS (1 M in THF) (212 mL of 1 M, 212 mmol) was added at such a rate as to keep the temperature below -65 C. On complete addition, the mixture was stirred at -78 C for a further 10 minutes before a solution of 2- (chloromethyl)isoindoline-1,3-dione (41.6 g, 213 mmol) in THF (230 mL) was added at such a rate as to keep the temperature below -65 C. On complete addition, the dry ice/acetone cooling bath was removed and the reaction flask was placed in an ice/water bath. The reaction mixture was allowed to warm to 0 C over 30 minutes. The mixture was re-cooled to -78 C before being quenched carefully with saturated aqueous NH4Cl solution (93 mL) at such a rate as to keep the internal temp below -65 C. On complete addition the cooling bath was removed and the mixture allowed to warm to ambient temperature. EtOAc (500 mL) was added and the organic phase separated. The organic phase was washed with water (x 2), brine, dried (MgSO4), filtered and concentrated in vacuo. IPA (500 mL) was added to the residue and the resulting solution left to stand over the weekend. The resulting crystallised solid was collected by filtration, washed with minimal IPA and dried under vacuum to give benzyl (2S,3S,5S)-3-[(1,3-dioxoisoindolin-2- yl)methyl]-2,5-dimethyl-4-oxo-piperidine-1-carboxylate (31 g, 42%) as a colourless solid; 1H NMR (400 MHz, DMSO-d6) delta 7.95 – 7.78 (m, 5H), 7.49 – 7.24 (m, 6H), 5.25 – 5.07 (m, 2H), 4.73 – 4.53 (m, 1H), 4.33 (t, 1H), 3.95 – 3.75 (m, 2H), 3.01 (s, 2H), 2.70 – 2.57 (m, 1H), 1.11 (d, 3H), 0.88 (d, 3H); MS m/z: 421 (M+H)+.

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; VERTEX PHARMACEUTICALS INCORPORATED; BAYLY, Andrew; BLEICH, Matthew; CHARRIER, Jean-Damien; DODD, James; DURRANT, Steven; ENO, Meredith Suzanne; ETXEBARRIA I JARDI, Gorka; EVERITT, Simon; FRAYSSE, Damien; KELLY, Shazia; KNEGTEL, Ronald; MOCHALKIN, Igor; MORTIMORE, Michael; NORTH, Kiri; PORICHIS, Filippos; PULLIN, Robert; RUTHERFORD, Alistair; STORCK, Pierre-Henri; TWIN, Heather Clare; XIAO, Yufang; (1159 pag.)WO2019/148132; (2019); A1;,
Indoline – Wikipedia,
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Related Products of 5428-09-1, 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. 5428-09-1, name is 2-Allylisoindoline-1,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 2-allylisoindoline-1,3-dione I1 (13.0 g, 69.4 mmol) in CH2Cl2 (500 mL) was added AllylTMS (79.0 g, 110 mL, 694 mmol) and Grubbs I generation catalyst. The reaction was heated to 60¡ã C. and stirred under reflux for 4 h. Tris(hydrodxymethyl)phosphine (1 M solution in i-PrOH, 58 mL) was added and stirred under reflux for 12 h, while the color of the reaction turned from black to orange. Sat. aq. NaCl solution (100 mL) was added to the reaction and the organic phase was separated. The aqueous phase was extracted with CH2Cl2 (3¡Á200 mL). The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. Column chromatography over SiO2 (Cyclohexane/EtOAc=85:15) afforded the title compound (15.0 g, 54.9 mmol, 78.9percent) as a yellow resin. (0400) Rf: 0.57 (Cyclohexane/EtOAc=85:15) (0401) 1H NMR (300 MHz, CDCl3) delta=?0.10-0.09 (m, 9H), 1.44 (d, J=8.2 Hz, 1.6H), 1.72 (d, J=8.8 Hz, 0.4H), 4.21 (d, J=6.5 Hz, 1.6H), 4.29 (dd, J=14.5, 5.9 Hz, 0.4H), 5.26-5.47 (m, 0.8H), 5.56-5.70 (m, 0.2H), 5.70-5.87 (m, 0.8H), 5.94-6.09 (m, 0.2H), 7.65-7.74 (m, 2H), 7.79-7.88 (m, 2H). (0402) 13C NMR (75 MHz, cdcl3) delta=?2.05, ?1.83, ?1.43, 18.92, 22.73, 34.72, 39.87, 120.51, 121.30, 123.12, 130.78, 132.24, 133.76, 133.90, 167.99.

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-Allylisoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Max-Planck-Gesellschaft zur Forderung der Wissensc haften e.V.; Wang, Yansong; Hausch, Felix; Bischoff, Matthias; Pomplun, Sebastian; (121 pag.)US2017/2003; (2017); A1;,
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Application 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.

General procedure: To a mixture of oxindole (3a-f, 0.3mmol), 1-alkyl-1H benzo[d]imidazole-2-carbaldehydes (7a-e, 0.33mmol) in ethanol (2mL), was added catalytic amount of piperidine. The reaction mixture was stirred at reflux until complete consumption of the oxindole observed by TLC. After cooling, the precipitate was filtered, washed with cold ethanol, and dried in air to furnish pure (E)-benzo[d]imidazol-2-yl)methylene)indolin-2-ones 8a-z orange/yellow solids in moderate to good yields. Compounds 8c, 8f, 8i, 8l and 8o did not precipitated out from ethanol, were purified by column chromatography with silica gel (60-120) by using ethyl acetate:hexane (2:8 to 3:7). 4.1.1.15 (E)-3-((1-isopropyl-1H-benzo[d]imidazol-2-yl)methylene)-5-methylindolin-2-one (8o) Yellow solid, Yield 79%; mp: 223-225 C; FT-IR: (cm-1): 3185, 3055, 1701, 1606, 1314, 813, 735; 1H NMR (500 MHz, DMSO-d6): delta 10.61 (brs, 1H, NH), 9.13 (s, 1H, Ar-H), 7.86-7.81 (m, 2H, Ar-H), 7.60 (s, 1H, C=CH), 7.37-7.28 (m, 2H, Ar-H), 7.14 (d, J = 7.8 Hz, 1H, Ar-H), 6.78 (d, J = 7.8 Hz, 1H, Ar-H), 5.17-5.06 (m, 1H, CH), 2.31 (s, 3H, CH3), 1.65 (d, J = 6.9 Hz, 6H, 2CH3); 13C NMR (75 MHz, CDCl3+DMSO-d6): delta 169.5, 146.6, 143.4, 140.8, 133.1, 132.1, 131.2, 130.5, 127.7, 123.3, 122.1, 120.9, 120.1, 117.9, 111.5, 109.2, 47.9, 21.6, 20.8; HRMS (ESI): m/z calcd for C20H20N3O 318.1606, found 318.1604 [M+H]+; Purity: 99.5%.

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

Reference:
Article; Sharma, Pankaj; Thummuri, Dinesh; Reddy, T. Srinivasa; Senwar, Kishna Ram; Naidu; Srinivasulu, Gannoju; Bharghava, Suresh K.; Shankaraiah, Nagula; European Journal of Medicinal Chemistry; vol. 122; (2016); p. 584 – 600;,
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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. 552330-86-6, name is 5-Bromoisoindolin-1-one, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C8H6BrNO

To R8 (100 mg, 0.47 mmol) in anhydrous dioxane (8 mL) is added R5 (180 mg, 0.71 mmol) and potassium acetate (140 mg, 1.43 mmol). The mixture is purged with Argon, PdCl2(dppf) (40 mg, 0.049 mmol) added and heated to 80 C. for 1.5 h. The reaction mixture is diluted with EA and water, the organic layer washed with brine, dried and concentrated. The crude product is carried on. m/z 260 [M+H]+, rt 0.64 min, LC-MS Method b.

According to the analysis of related databases, 552330-86-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; GRUNDL, Marc; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; RIETHER, Doris; WIENEN, Wolfgang; US2013/172327; (2013); A1;,
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Synthetic Route of 61-70-1, 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. 61-70-1, name is 1-Methylindolin-2-one, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: An oven-dried reflux tube equipped with a magnetic stir bar and a Teflon stopcock was charged with aryl halide (1 mmol), oxindole (1 mmol),potassium carbonate (1.1 mmol), catalyst nanoparticles (0.05 mmol)and 1,4-dioxane (2 ml) and heated at 70 C. The mixture was vigorously stirred under these reaction conditions and completion of the reaction was monitored by TLC (EtOAc: n-hexane, 25:75). After completion of the reaction, the reaction mixture was cooled to room temperature, the magnetic nanoparticles of the catalyst were collected using a magnet. Ethyl acetate (5 mL) and water (10 mL)were added to the mixture in the next step. The aqueous layer was furtherextracted by ethyl acetate (2*5 mL). The combined organic layerswere washed with saturated brine, dried over CaCl2, filtered, and concentrated to give a residue which was purified by recrystallization from ethanol and water or by column chromatography on silica gelusing EtOAc: n-hexane, 1:7.

The chemical industry reduces the impact on the environment during synthesis 1-Methylindolin-2-one. I believe this compound will play a more active role in future production and life.

Reference:
Article; Moghaddam, Firouz Matloubi; Tavakoli, Ghazal; Latifi, Fatemeh; Saeednia, Borna; Catalysis Communications; vol. 75; (2016); p. 37 – 41;,
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Electric Literature of 17564-64-6, 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. 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

Benzyl 3-methyl-4-oxo-piperidine-1-carboxylate (20 g, 0.08 mol) was dissolved in THF (300 mL) under N2. The solution was cooled to -78 C and LiHMDS (1 M in THF, 101.1 mL, 0.1 mol) was added dropwise over 20 minutes, keeping the temperature below -70 C. After stirring at -78 C for 90 minutes, a solution of 2-(chloromethyl)isoindoline-1,3-dione (23.7 g, 0.12 mol) in THF (200 mL) was added dropwise over 25 minutes, keeping the temperature below -70 C. The reaction was stirred at -78 C for 1 hour then quenched at -78 C by the addition of saturated aqueous ammonium chloride solution (65 mL) and the mixture allowed to warm to ambient temperature. The reaction was repeated and the two mixtures obtained were combined and extracted with EtOAc (300 mL). The organic phase was washed with saturated aqueous sodium bicarbonate solution (300 mL) and brine (300 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, EtOAc/PE elution). The product fractions were combined and concentrated in vacuo and the residue recrystallized from EtOAc to give benzyl 3-((1,3-dioxoisoindolin-2-yl)methyl)-5-methyl-4- oxopiperidine-1-carboxylate as a white solid (7.56 g, 23%).

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

Reference:
Patent; MERCK PATENT GMBH; VERTEX PHARMACEUTICALS INCORPORATED; BAYLY, Andrew; BLEICH, Matthew; CHARRIER, Jean-Damien; DODD, James; DURRANT, Steven; ENO, Meredith Suzanne; ETXEBARRIA I JARDI, Gorka; EVERITT, Simon; FRAYSSE, Damien; KELLY, Shazia; KNEGTEL, Ronald; MOCHALKIN, Igor; MORTIMORE, Michael; NORTH, Kiri; PORICHIS, Filippos; PULLIN, Robert; RUTHERFORD, Alistair; STORCK, Pierre-Henri; TWIN, Heather Clare; XIAO, Yufang; (1159 pag.)WO2019/148132; (2019); 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. 5394-18-3, name is 2-(4-Bromobutyl)isoindoline-1,3-dione, A new synthetic method of this compound is introduced below., name: 2-(4-Bromobutyl)isoindoline-1,3-dione

General procedure: A mixture of the intermediates 3a-3e (5 mmol) and corresponding secondary amine 4a-4g (5.5 mmol) was added in CH3CN (20 ml) at the presence of anhydrous K2CO3 (6 mmol). The mixture was heated at 65 C for 6-10 h. The solvent was evaporated in vacuo. The residue was dissolved in CH2Cl2 (25 mL), washed with water (20 mL ¡Á 3), and the combined organic phases were washed with saturated aqueous NaCl (30 mL), dried over sodium sulfate, and filtered. The solvent was evaporated under reduced pressure. The residue was purified on a silica gel chromatography using mixtures of petroleum/acetone as eluent to get the target products TM-1~TM-28.

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; Sang, Zhipei; Wang, Keren; Wang, Huifang; Yu, Lintao; Wang, Huijuan; Ma, Qianwen; Ye, Mengyao; Han, Xue; Liu, Wenmin; Bioorganic and Medicinal Chemistry Letters; vol. 27; 22; (2017); p. 5053 – 5059;,
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Adding a certain compound to certain chemical reactions, such as: 5332-26-3, name is 2-(Bromomethyl)isoindoline-1,3-dione, 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 5332-26-3, Recommanded Product: 2-(Bromomethyl)isoindoline-1,3-dione

(S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-10-oxo-heptadec-2-enyl}-2-hydroxy-succinate To a mixture of No. 5317776 (Compound E; 60 mg, 0.08 mmol), DBU (19 muL, 0.126 mmol) and dichloromethane (0.84 mL) was added 2-bromomethyl-isoindole-1,3-dione (30 mg, 0.126 mmol) commercially available from Aldrich (cat. No. 252611). After the mixture was stirred at room temperature for 6 hours, further 2-bromomethyl-isoindole-1,3-dione (10 mg, 0.04 mmol) and DBU (6.3 muL, 0.04 mmol) were added. Then, 4-(1,3-dioxo-1,3-dihydro-isoindole-2-ylmethyl) 1-butyl (S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-10-oxo-heptadec-2-enyl}-2-hydroxy-succinate (56 mg, 76%) was obtained (ESI (LC/MS positive mode) m/z 873 (M+H); Rt 3.38 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; Chugai Seiyaku Kabushiki Kaisha; KOHCHI, Yasunori; NAKAMA, Kimitaka; KOMIYAMA, Susumu; WATANABE, Fumio; EP2886530; (2015); A1;,
Indoline – Wikipedia,
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