Author: Jessica.F

Some common heterocyclic compound, 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, molecular formula is C8H4KNO2, 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. Safety of Potassium 1,3-dioxoisoindolin-2-ide

To a stirred solution of 1,5-dibromopentane (13-k) (170.58 mL, 1.26 mol) in DMF (1.5 L) was added potassium phthalate (12-k) (78.0 g, 0.42 mol) portion-wise over 30 mm at room temperature. After complete addition, the reaction mixture was stirred at 90C for 18 h, then quenched with water (3 L) and extracted with diethyl ether (500 mL x 4). The combined organic extracts were washed with water (500 mL x 2), followed by brine (500 mL x 2) and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The residue was purified by silica gel column chromatography (60-120 mesh) using 5-10% EtOAc / hexanes to afford 14-k as an off-white solid (81 g, 65% yield). ?HNMR (400 IVIFIz, CDC13): 7.82 (dd, J= 5.5, 3.1 Hz, 2H), 7.69 (dd, J 5.5, 3.0 Hz, 2H), 3.68 (t, J 7.2 Hz, 2H), 3.38 (t, J 6.8 Hz, 2H), 1.93-1.85 (m, 2H), 1.70 (p, J= 7.5 Hz, 2H),1.53-1.43 (m, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1074-82-4, its application will become more common.

Reference:
Patent; CV6 THERAPEUTICS (NI) LIMITED; SPYVEE, Mark; LEWIS, Michael; (300 pag.)WO2018/98204; (2018); A1;,
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Electric Literature of 201940-08-1, 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. 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of tert-butyl 5-bromoisoindoline-2-carboxylate (1.20 g, 4.02 mmol, CAS201940-08-1), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.12 g, 4.43 mmol) in DMSO (20.0 mL) was added KOAc (1.18 g, 12.0 mmol) and Pd(PPh3)4 (139 mg, 120 umol). The mixture was stirred at 80 C. for 16 hours under N2. On completion, the mixture was diluted with H2O (50 mL), and extracted with EA (3¡Á30 mL). The organic layers were washed with brine (3¡Á30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The mixture was purified by prep-HPLC (reserve phase (0.1% FA)) to give the title compound (500 mg, 36% yield) as yellow solid. 1H NMR (400 MHz, CDCl3) delta 7.75 (s, 1H), 7.32-7.29 (m, 1H), 7.25 (d, J=7.6 Hz, 1H), 4.74-4.66 (m, 4H), 1.54 (s, 9H), 1.37 (s, 12H).

The chemical industry reduces the impact on the environment during synthesis tert-Butyl 5-bromoisoindoline-2-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Kymera Therapeutics, Inc.; Mainolfi, Nello; Ji, Nan; Kluge, Arthur F.; Weiss, Matthew M.; Zhang, Yi; (1443 pag.)US2019/192668; (2019); A1;,
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Synthetic Route of 56341-37-8, 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 56341-37-8 as follows.

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%).

According to the analysis of related databases, 56341-37-8, the application of this compound in the production field has become more and more popular.

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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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. 317-20-4, name is 7-Fluoroisatin, A new synthetic method of this compound is introduced below., Product Details of 317-20-4

General procedure: A mixture of 1 (0.4 mmol), 2 (0.4 mmol), Na2CO3 (0.8 mmol) and TBHP (0.4 mmol) in DMF (4 mL) was stirred at rt for 2 h. Then, the mixture was poured into ice-water, acidified with 1 N HCl aq. (6 mL). The mixture was extracted with ethyl acetate (20 mL x 3). The combined organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by silica gel flash column chromatography to give desired products.

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; Wu, Jun; Zhang, Hui; Ding, Xiao; Tan, Xuefei; Shen, Hong C.; Chen, Jie; He, Weimin; Deng, Hongmei; Song, Liping; Cao, Weiguo; Journal of Fluorine Chemistry; vol. 220; (2019); p. 54 – 60;,
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These common heterocyclic compound, 59-48-3, name is 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. name: Indolin-2-one

To a solution of 1,3-Dihydro-indol-2-one (20 g, 133.15 mmol) in acetonitrile (300 ml) at 0 C. was added NBS (30.76 gm, 173.8 mmol) in several portions and the solution stirred at this temperature for 3 h. Water was added to the reaction mixture, upon which a white solid precipitated. The solid was collected by filtration, washed with hot water and dried under vacuum to obtain compound 5-Bromo-1,3-dihydro-indol-2-one (28 g, 88%).

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

Reference:
Patent; Alam, Muzaffar; Du Bois, Daisy Joe; Hawley, Ronald Charles; Kennedy-Smith, Joshua; Minatti, Ana Elena; Palmer, Wylie Solang; Silva, Tania; Wilhelm, Robert Stephen; US2011/71150; (2011); A1;,
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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 923590-95-8 as follows. Application In Synthesis of 4-Bromoisoindoline hydrochloride

3. Kumada Coupling of Bromo-Iso-Indole [0258] bromoisoindoline HCl salt (25 g, 106.6 mmol), Pd(OAc)2 (0.199 g, 0.533 mmol), and the ligand (di-tert-butylneopentylphosphonium tetrafluoroborate, 0.325 g, 1.066 mmol). PhMe (toluene) (450 mL, de-oxygenated via sparging with N2) was then added, and the resulting slurry was then cooled to Ti=5 C. using an external bath. Allylmagnesium chloride (1.7 N in THF, 207 mL, 351.8 mmol) was charged to an addition funnel via cannula, and then added at a rate such that Ti<20 C. The resulting solution was then was heated to Ti=45-50 C. [0260] After 16 hours, LC showed >99% conversion of starting material. The reaction was cooled to room temperature, and then was inverse-quenched into 250 mL of 15% aqueous citric acid. The phases were separated, and the aqueous phase containing the product was held while the dark organic phase was rejected. The extractor that contained the aqueous phase was charged with 125 mL of PhMe. The pH of the aqueous phase was adjusted by the addition of 115 mL of NH4OH. The phases were separated, and the organic phase containing the product was held while the aqueous phase was rejected. The organic phase was washed with 20 mL of 15% aqueous NaCl. The PhMe solution was concentrated with azeotrope to a 10 volume solution (KF<2000 ppm H2O). [0261] This PhMe solution of product was transferred to 250 mL flask with overhead stirring. An addition funnel was charged with 17.5 mL of 5.33 M HCl in IPA (5.3 M), which was added slowly over 20 minutes. The resulting slurry was aged for 30 minutes at Ti=40 C., and then was gradually cooled to Ti=20-22 C. over 30 minutes. After aging for 1 hour, the slurry was slowly cooled to Ti=0 C. over 30 minutes by use of an external bath. After 30 minutes, the slurry was filtered. The cake was washed with 16 mL of cold (Ti=-10 vC) 14:2 PhMe:IPA. The cake was then washed with 15 mL of ambient temperature (Ti=22 C.) MTBE. After drying, 7.6 g of allyl isoindoline was isolated as an off white solid. The isolated product assayed for 98.7 wt %. According to the analysis of related databases, 923590-95-8, the application of this compound in the production field has become more and more popular. Reference:
Patent; Chen, Cheng; Kong, Jongrock; Humphrey, Guy; Dolman, Sarah; Li, Hongmei; Tudge, Matthew T.; Yong, Kelvin; Xiang, Bangping; Zacuto, Michael; US2013/274463; (2013); A1;,
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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. Safety of Indolin-2-one

Sodium hydride (9.0 g; 0.2 mol, 60% in mineral oil) was added portion-wise to a solution of oxindole (10.0 g, 75 mmol) in of dry DMF (350 mL). After 15 minutes, the reaction was cooled to 0 C. and 1,4 dibromoethane in 100 mL of dry DMF was added over 15 minutes. The dark brown reaction was allowed to warm to room temperature and stirred overnight. The reaction was diluted with ethyl acetate and water was added. The layers were separated and the organic layer was dried over anhydrous sodium sulfate. The organic layer was filtered, concentrated in vacuo to give 20 g of red oil. The crude product was purified on silica using a stepwise gradient of 10% to 20% ethyl acetate: hexane to afford Spiro[cyclopropane-1,3′-[3H]indol]-2′(1’H)-one (2.3 g, 11%).

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

Reference:
Patent; Wyeth; US2006/30615; (2006); A1;,
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Application of 6341-92-0, The chemical industry reduces the impact on the environment during synthesis 6341-92-0, name is 6-Chloroisatin, I believe this compound will play a more active role in future production and life.

General procedure: In a 25 mL round bottom flask, isatins 1 (1 mmol), 3-phenylisoxazol-5(4H)-one 2 (1 mmol) or 3-ethylisoxazol-5(4H)-one 7 (1 mmol), pyrazol-5-amine 3 (1 mmol) or 6-aminopyrimidine-2,4-(1H,3H)-dione 5 (1 mmol), and Amberlyst-15 (100 mg) were stirred in CH3OH (5.0 mL) at 80 C. When the reaction was completed (detected by TLC), the spherical catalyst was separated by a sieve at once under hot condition. Then, the reaction mixture was cooled to room temperature, and solid precipitation occurred. After filtration, the crude product was recrystallized from EtOH and DMF to give pure compound.

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-Chloroisatin, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Niu, Qingqing; Xi, Junhua; Li, Lei; Li, Li; Pan, Chengli; Lan, Meijun; Rong, Liangce; Tetrahedron Letters; vol. 60; 43; (2019);,
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These common heterocyclic compound, 132898-96-5, name is 2,3-Dioxoindoline-5-sulfonyl chloride, 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. Safety of 2,3-Dioxoindoline-5-sulfonyl chloride

Step 3: 5-({(2S)-2-[(4-methylpiperazin-1-yl)methyl]pyrrolidin-1-yl}sulfonyl)-1H-indole-2,3-dione The title compound was prepared from 2,3-dioxo-2,3-dihydro-1H-indole-5-sulfonylchloride and 1-methyl-4-[(2S)-pyrrolidin-2-ylmethyl]piperazine according to a procedure similar to that of step 1 of Example 12. NMR (400 Mz, DMSO-d6): consistent.

The synthetic route of 2,3-Dioxoindoline-5-sulfonyl chloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Wyeth; US2005/250798; (2005); A1;,
Indoline – Wikipedia,
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Application of 6941-75-9, 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 6941-75-9 as follows.

Step 1: tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate To a solution of 5-bromo-1H-isoindole-1,3(2H)-dione (4 mmol) in THF (10 mL) was added borane-dimethyl sulfide complex (2M in THF, 14 mL) at 0 C. The reaction mixture was allowed to stir at reflux overnight and was then cooled to 0 C. The reaction mixture was quenched by the slow addition of MeOH (10 mL) and then 2N HCl (10 mL). The reaction mixture was allowed to stir at reflux for 3 hr and then concentrated. Water (10 mL) was added to the residue. Remaining starting material was removed by extraction with DCM. To the aqueous solution was added 4N NaOH until pH>9. The solution was extracted with DCM. The organic solutions from this basic extraction were combined, dried over Na2SO4, filtered and concentrated to give 5-bromoisoindoline, which was dissolved in THF (20 mL). To this solution was added potassium carbonate (8 mmol) in water (1 mL), and BOC2O. The reaction mixture was allowed to stir at rt over the weekend. The reaction mixture was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (2.5 mmol, 60%).

According to the analysis of related databases, 6941-75-9, the application of this compound in the production field has become more and more popular.

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