Author: Jessica.F

Reference of 39603-24-2, 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. 39603-24-2 name is 5,7-Dimethylindoline-2,3-dione, 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.

General procedure: A mixture of isatins 1a-g (1 mmoL) with an equimolar amount of N,N’-diphenyl/(p-tolyl)thiourea2a,b (1 mmoL) and bromoacetic acid 3 (0.14 g, 1 mmoL) in glacial acetic acid (10 mL) in the presenceof sodium acetate (0.16 gm, 2 mmoL), was heated under reflux for 3 h. The formed solid was filteredoff while hot, washed with hot ethanol, dried and recrystallized from DMF to furnish the targethybrids 4a-n.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5,7-Dimethylindoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Article; El-Naggar, Mohamed; Eldehna, Wagdy M.; Almahli, Hadia; Elgez, Amr; Fares, Mohamed; Elaasser, Mahmoud M.; Abdel-Aziz, Hatem A.; Molecules; vol. 23; 6; (2018);,
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Synthetic Route of 611-09-6, 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. 611-09-6 name is 5-Nitroindoline-2,3-dione, 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.

General procedure: A mixture of an isatin (1mmol), molononitrile (1mmol), CH activatedacid (1mmol), and [C4(DABCO)2]·2OH(2mol%) inwater (3mL)was stirred at 80 C. The reaction progress was monitored by TLC [eluent:n-hexane:EtOAc (9:2)] (It is important to that by beginning of thereaction the products were precipitated in the reaction medium).After completion of the reaction, the mixture was cooled to room temperature and the solid product was filtered, washed with cold distilledwater (2 mL) to obtain essentially pure products. The solid productswere recrystallized from ethanol if necessary.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Nitroindoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Article; Goli-Jolodar, Omid; Shirini, Farhad; Seddighi, Mohadeseh; Journal of Molecular Liquids; vol. 224; (2016); p. 1092 – 1101;,
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Synthetic Route of 6780-38-7,Some common heterocyclic compound, 6780-38-7, name is 2-(1,3-Dioxoisoindolin-2-yl)acetyl chloride, molecular formula is C10H6ClNO3, 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.

271 g of water was put in a 1 L four-necked flask and cooled to 10 C. 7 7 g (570.4 mmol) of potassium carbonate was added thereto and dissolved. This was cooled to 3 C. and 30.1 g (223.2 mmol) of 2,2,2-trifluoroethylamine hydrochloride was added thereto. The solution was stirred at 3 C. for 10 minutes, and a solution of 50 g (223.2 mmol) of phthaloylglycyl chloride dissolved in 150.7 g of acetonitrile was added dropwise thereto at such a rate that the reaction solution kept at 20 C. or lower. After stirring for 1 hour, the product precipitated in the reaction was filtered and washed with 150.7 g of water. The obtained solid was dried under reduced pressure at 60 C. to obtain 2-phthaloyl-N- (2,2,2-trifluoroethyl) acetamide as a white solid. The yield was 59.7 g, and the yield was 93.5%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(1,3-Dioxoisoindolin-2-yl)acetyl chloride, its application will become more common.

Reference:
Patent; Nissan Chemical Industries, Ltd.; Moriyama, yuji; (16 pag.)JP5652628; (2015); B2;,
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Adding a certain compound to certain chemical reactions, such as: 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, 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 201940-08-1, Computed Properties of C13H16BrNO2

Example 3-91 a 2,3-Dihydro-1H-isoindole-5-carboxylic acid methyl ester was synthesised according to the following scheme: A mixture of 5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (200 mg, 0.67 mmol), Pd(OAc)2 (30 mg, 0.2 equiv), DPPP (55 mg, 0.2 equiv), TEA (0.93 mL, 10 equiv) and MeOH:DMSO (1:1, 4 mL) was stirred for 16 h under CO (balloon) at 80 C. LC-MS and TLC (20% EtOAc-Hexane) showed completion of the reaction. The Reaction mixture was concentrated to remove MeOH and diluted with EtOAc (10 mL), and washed with water (2*25 mL). The organic layer was dried (Na2SO4), concentrated and purified by silica gel column chromatography (eluent=20% EtOAc-Hexane), giving pure 1,3-dihydro-isoindole-2,5-dicarboxylic acid 2-tert-butyl ester 5-methyl ester (150 mg, 81%). MS (APCI+): m/z 178.1 (MH+-Boc).

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, tert-Butyl 5-bromoisoindoline-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Blatt, Lawrence M.; Andrews, Steven W.; Condroski, Kevin R.; Doherty, George A.; Jiang, Yutong; Josey, John A.; Kennedy, April L.; Madduru, Machender R.; Stengel, Peter J.; Wenglowsky, Steven M.; Woodard, Benjamin T.; Woodard, Laura; US2005/267018; (2005); A1;,
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172078-33-0, name is Indolin-5-ol, 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. Application In Synthesis of Indolin-5-ol

Example 40 5-(6-(5-hydroxyindoline-1-carbonyl)pyrimidin-4-ylamino)-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1’H)-one 0.15 g (0.37 mmol) 6-(2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-5-ylamino)pyrimidine-4-carboxylic acid hydrochloride, 50 mg (0.37 mmol) 2,3-dihydro-1H-indol-5-ol, 150 muL (0.87 mmol) DI PEA and 0.13 g (0.41 mmol) TBTU in 1.8 mL DMF were stirred overnight at RT. The purification was carried out by preparative HPLC-MS. The product-containing fractions were combined and lyophilised. Yield: 44 mg (23% of theory) ESI-MS: m/z=491 (M+H)+ Rt (HPLC-MS): 1.33 min (method C)

The synthetic route of 172078-33-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2011/21500; (2011); 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. 143262-20-8, name is 1-(tert-Butoxycarbonyl)indoline-7-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 1-(tert-Butoxycarbonyl)indoline-7-carboxylic acid

(1) 7-Indolinecarboxamide To a mixture of 1-(tert-butoxycarbonyl)-7-indolinecarboxylic acid (3.67 g, 13.9 mmol), chloroform (30 mL) and a drop of dimethyl formamide was added dropwise with stirring oxalyl chloride (5.5 mL, 63.0 mmol) over a period of 5 minutes at room temperature. After the addition, the reaction mixture was warmed to 60 C., and stirred at 60 C. for 2 hours. The reaction mixture was concentrated under reduced pressure, and thereto was added toluene (about 100 mL), and the mixture was further concentrated under reduced pressure. To the residue was added tetrahydrofuran (80 mL), and thereto was added with stirring a 29% aqueous ammonia (55 mL) with stirring under ice-cooling. The mixture was warmed to room temperature and stirred overnight. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with a saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (SiO2, hexane:ethyl acetate=1:2, and then ethyl acetate) to give 7-indolinecarboxamide (2.02 g, yield: 90%). 1H NMR (DMSO-d6) 67; 7.62 (br, 1H), 7.36 (d, 1H, J=8.1 Hz), 7.08 (d, 1H, J=7.0 Hz), 7.00 (br, 1H), 6.61 (s, 1H), 6.46-6.41 (m, 1H), 3.52 (t, 2H, J=8.5 Hz), 2.90 (t, 2H, J=8.5 Hz)

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 143262-20-8.

Reference:
Patent; Masumoto, Shuji; Kitano, Masahumi; Ohashi, Naohito; US2003/105118; (2003); A1;,
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Application of 1504-06-9, 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. 1504-06-9, name is 3-Methyloxindole belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a Schlenk bottle, add the 2-indolinone compound (29.4 mg, 0.2 mmol) represented by Formula 1a,Copper nitrate (56.1 mg, 0.3 mmol), potassium persulfate (K2S2O8, 81.0 mg, 0.3 mmol) and ethyl acetate (2 mL) shown in formula 2a,Then, the reactor was stirred under the air atmosphere at 25 C.The reaction progress was monitored by TLC until the raw materials disappeared (reaction time was 2h). After the reaction was completed,Ethyl acetate was further added to the reaction solution, the solid residue was removed by filtration, and the solvent was concentrated under reduced pressure.The target product I-1 (90% yield) can be obtained;

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

Reference:
Patent; Yangtze Normal University; Wu Yan; Chen Jinyang; Liu Jialing; Zhong Chuntao; (9 pag.)CN110590639; (2019); A;,
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Application of 2058-72-2, These common heterocyclic compound, 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-dione, 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 mixture of 2- (1-benzyl-2-oxoindol-3-yl) acetic acid67.4 mg (0.24 mmol),5-Bromo-1-methyl isatin 47.7mg (0.2mmol),N, N’-2- (7-benzo benzotriazole) -N, N, N ‘, N’-tetramethyluronium hexafluorophosphate (106.4 mg, 0.28 mmol)Triethylamine 50.6 mg (0.5 mmol)And 2 mL of tetrahydrofuran were placed in a 25 mL two-necked flask,Reaction at 0 C for 6 h,The reaction solution was concentrated,Eluting with a mixed solvent of petroleum ether: ethyl acetate ratio of 3: 1 as elution column,Collecting the eluted fraction of all the products detected,Rotate the solvent to give the product 90.3mg,The yield was 90% and the Dr value was 4: 1.

Statistics shows that 5-Bromo-1-methylindoline-2,3-dione is playing an increasingly important role. we look forward to future research findings about 2058-72-2.

Reference:
Patent; China Pharmaceutical University; Du Ding; Cao Jing; Dong Shuding; (14 pag.)CN106749295; (2017); A;,
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These common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, 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. category: indolines-derivatives

4,7-Dichloroisotin (30.05 g, 139.1 mmol, 1.0 equiv, Alfa Aesar lot 10173559) and MeOH (450 mL, 15 vol) were charged to a 2-L, three-neck, round-bottom flask equipped with nitrogen line, overhead mechanical stirrer, and a temperature probe. Diethylamine (3.25 g, 0.32 equiv, Sigma- Aldrich lot SHBD5313V) was added over 3 min (the slurry becomes dark red). A very slight increase in temperature (from 17.5 C to 18.8 C) was observed. 1- [4-(Dimethylamino)phenyl]ethanone 2 (44.3 g, 1.95 equiv, ArkPharm lot 0000197- 130717000) was then added via a plastic funnel and the funnel was rinsed with MeOH (75 mL, 2.5 vol). A decrease in the reaction temperature to 15.1 C was observed. Upon stirring for a few minutes, a dark red solution with a few undissolved particles was obtained. The solution was stirred at ambient temperature and periodically sampled for in-process control (IPC) by HPLC. After 23 h of reaction, additional diethylamine was added via syringe (1.42 g, 0.14 equiv) and the stirring continued at ambient temperature. After 40.5 h, a light slurry formed. Solid 2 was added in portions (54.1 g, 2.38 equiv, ArkPharm lot 0000197- 130717000 and 3.2 g, 0.14 equiv, TCI lot GK01-BRAH) for a total of 4.47 equiv of acetophenone 2. After 88 h of reaction, IPC by HPLC showed less than 1% AUC of isatin 1 present in the reaction mixture. A heavy precipitate had formed. After 4.5 days, the reaction mixture was concentrated under reduced pressure (water bath <40 C), then under high vacuum to afford approximately 84 g of a solid mixture, lot BIO-W-22-11. The solid was dissolved in a mixture of dichloromethane (385 mL) and MeOH (140 mL) and adsorbed over 100 g of silica gel. The solvent was removed under reduced pressure and the dry product/silica mixture was loaded onto a column containing silica gel (1 kg, pre-packed with heptanes) for a flash chromatographic purification. Elution was started with 10% ethyl acetate in heptanes and a gradient up to 100% ethyl acetate was applied, and then switched to 10% methanol in ethyl acetate. Fractions of 500 mL and up to 2 L were collected. The product containing fractions, where product had started to precipitate, were combined and concentrated down to approximately 1 L. The resulting precipitate was filtered out, reslurried in EtOAc/MeOH (75:25 ratio, 200 mL), filtered, and washed with MeOH to afford a first crop of compound. The first filtrate was concentrated to a low volume, added MeOH to precipitate a second crop of compound. Filtrates from isolation of both crops were combined, concentrated to a low volume, taken up in 25 mL of MeOH, and the resulting solid was filtered to afford a third crop of compound. All three crops were dried under high vacuum at ambient temperature for a day and at 40 C for four days. The total combined weight was 40.03 g, corresponding to 76% yield of compound (uncorrected by purity or solvent content). Solid is off-white (with a very pale yellow to peach shade. The synthetic route of 4,7-Dichloroindoline-2,3-dione 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. 446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, A new synthetic method of this compound is introduced below., Recommanded Product: 446292-08-6

2-({(5S) -2-oxo-3-[4- (3-oxo-4-morpholinyl) phenyl] -1,3-oxazolidin-5- yl} methyl)-1,3(2H) -dione (Formula 5) were added 75 ml of ethanol and 8.1 ml of a methylamine solution (concentration in water 40%) was added.The reaction mixture was then diluted with 60In Heating, Stir at this temperature for 2 hours.Confirm that the reaction is completed, and while maintaining the temperature, dilute the solution with 50 ml of ethanol and 3.04 ml of phosphoric acid, and slowly add the solution to the reaction solution. After confirming that the crystallization of the product was initiated and cooling to 20 C, the precipitated reaction product was filtered under suction. The resulting solid was dispersed in 110 ml of methanol, refluxed for 30 minutes and stirred, and then cooled to room temperature. The resulting crystals were filtered,And dried at 50 DEG C for 4 hours to obtain 11.1 g of morpholine diphosphate (Formula 2). (Yield: 96.0%)

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; IL DONG PHARMACEUTICAL CO., LTD.; LEE, Ki Yong; KWON, Jae Wook; SEO, Myeong Won; KANG, Jae Hoon; (15 pag.)KR2017/98031; (2017); A;,
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