Category: indolines-derivatives

Reference of 954-81-4,Some common heterocyclic compound, 954-81-4, name is N-(5-Bromopentyl)phthalimide, molecular formula is C13H14BrNO2, 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 suspension of compound 9 (12.0 g, 40.5 mmol) and potassium carbonate (14.0 g, 101 mmol) in THF (150 mL) was added dropwise an excess of a dimethylamine aqueous solution (26% wt) (39 mL, 202.5 mmol) and the reaction mixture was refluxed for 24 h. After cooling, the solution was filtered and the precipitate was washed with THF (200 mL). After concentration under reduced pressure, the filtrate afforded a biphasic residue that was decanted. The oily layer was separated to yield a first fraction of compound 13a. The remaining aqueous layer was extracted with EtOAc (2 × 75 mL), the organic extracts were combined, dried over MgSO4, filtered and evaporated under vacuum to afford a supplementary fraction of compound 13a. The two fractions (6.95 g, 34.0 mmol) were combined and engaged directly in the next step without further purification. Yield 84%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route N-(5-Bromopentyl)phthalimide, its application will become more common.

Reference:
Article; Ghedira, Donia; Voissiere, Aurelien; Peyrode, Caroline; Kraiem, Jamil; Gerard, Yvain; Maubert, Elise; Vivier, Magali; Miot-Noirault, Elisabeth; Chezal, Jean-Michel; Farhat, Farhat; Weber, Valerie; European Journal of Medicinal Chemistry; vol. 158; (2018); p. 51 – 67;,
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7477-63-6, name is 7-Chloroisatin, 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. COA of Formula: C8H4ClNO2

General procedure: To a mixture of isatin or isatin derivatives (1 mmol) in DMF (1.5 mL) was added dried K2CO3 (165.5 mg, 1.2 mmol). The resulting mixture was stirred at 70oC for 1 hour, then 83 mg of KI (0.5 mmol) was added followed by slow addition of a solution of 3,4,5-trimethoxybenzyl clorid (216.7 mg, 1 mmol) in DMF (1 mL). The reaction mixture was stirred for a further 3 hours at 80oC, then cooled to room temperature. Cold water (20 mL) was slowly added to the cooled reaction mixture and pH was adjusted to ~ 6 by a solution of HCl 5percent to generate yellowish to brown precipitates, which were filtered, washed by cold water until neutrality. The precipitates were recrystallized by EtOH/H2O and dried at 60oC under vacuum.

The synthetic route of 7477-63-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Huan, Le Cong; Pham-The, Hai; Le-Thi-Thu, Huong; Thao, Tran Phuong; Que, Do Nguyet; Trang, Nguyen-Thu; Dung, Phan Thi Phuong; Pyo, Minji; Han, Sang-Bae; Thuan, Nguyen Thi; Nam, Nguyen-Hai; Letters in drug design and discovery; vol. 15; 4; (2018); p. 375 – 387;,
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Synthetic Route of 102359-00-2, The chemical industry reduces the impact on the environment during synthesis 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, I believe this compound will play a more active role in future production and life.

Example 1 :(3Z)-3-[(4-{[2-(diethylamino)ethyl]carbamoyl}-3,5-dimethyl-1H-pyrrol- 2-yl)methylene]-2-oxoindoline-5-carboxylic acid (1)A mixture of 2-oxoindoline-5-carboxylic acid (0.708 g, 4 mmol), 3,5-dimethyl-4- (piperidin-1 -ylcarbonyl)-1 /-/-pyrrole-2-carbaldehyde (1 .030 g, 4.4 mmol) and piperidine (0.2 ml_) in EtOH (75 ml_) was refluxed for 8 h. The mixture was cooled down to room temperature to provide a precipitate which was filtered and washed with EtOH to provide the target compound 1 (0.980 g, 62.25%).NMR (300 MHz, DMSO-c/6) delta ppm: 13.52 (s,1 H), 12.5 (bs,1 H), 1 1 .19 (s,1 H), 8.37 (s,1 H), 7.78 (s,1 H), 7.77 (d,1 H), 6.96 (d,1 H), 3.43 (m,4H), 2.29 (s,6H), 1 .60 (bs,2H), 1 .47 (bs,4H); tR: 3.18 min, MS (ESI): m/z (M+H)+ 394; (M+HV392.

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-Oxoindoline-5-carboxylic Acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MAX-PLANCK-GESELLSCHAFT ZUR FOeRDERUNG DER WISSENSCHAFTEN E.V.; ULLRICH, Axel; FALCENBERG, Mathias; OeRFI, Zoltan; KERI, Gyoergy; OeRFI, Laszlo; HORVATH, Zoltan; SZOKOL, Balint; DOBOS, Judit; NEMES, Zoltan; WO2015/22437; (2015); 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. 39603-24-2, name is 5,7-Dimethylindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of 5,7-Dimethylindoline-2,3-dione

General procedure: To asolution of isatin 3 (1.0mmol), 2-aminopyridine 2 (1.35mmol)andisocyanide 4 (1.35mmol) in 4mL of n-butyl alcohol was added HClO4 (1.0mmol), and the reaction mixture was stirred under refluxfor 8 h. After cooling to room temperature, the precipitate was collected by filtration, rinsed with ethanol and dried to afford the target compound 1.

The synthetic route of 39603-24-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yang, Bo; Tao, Chuanye; Shao, Taofeng; Gong, Jianxian; Che, Chao; Beilstein Journal of Organic Chemistry; vol. 12; (2016); p. 1487 – 1492;,
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Reference of 7147-90-2,Some common heterocyclic compound, 7147-90-2, name is 5-Chloroisoindoline-1,3-dione, molecular formula is C8H4ClNO2, 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. Preparation of (2a) where R3 is 4-chloro To a solution of 4-chlorophthalimide (60 g) in 1 liter of tetrahydrofuran was added borane-methyl sulfide complex (100 ml of 10M), and the mixture was refluxed overnight. After cooling, 100 ml of 6N hydrochloric acid was added slowly, the mixture refluxed for 2 hours, and then filtered. The filtrate was concentrated under reduced pressure, and the resulting aqueous solution washed with ethyl acetate. The aqueous layer was then basified with ammonium hydroxide and extracted with methylene chloride. Solvent was removed from the extract, and the residue distilled under vacuum to give 4-chloroisoindoline, a white solid, m.p. 48-50 C.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Chloroisoindoline-1,3-dione, its application will become more common.

Reference:
Patent; Syntex (U.S.A.) Inc.; US5726197; (1998); A;,
Indoline – Wikipedia,
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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 446292-08-6 as follows. category: indolines-derivatives

10 g (0.024 mol) of 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1 ,3-oxazolidin-5- yl}methyl)-1 H-isoindole-1 ,3(2H)-dione (II), 7.12 mL of methylamine (40% aqueous solution, 0.083 mol) and 150 mL of methanol were charged in a 1 L autoclave and heated to reflux temperature (65.0C) for 1 hour. Afterwards, the reaction mass was cooled to 25-30C and transferred to another flask. Then, 9.9 g (0.095 mol) of malonic acid in 50 mL of methanol were added dropwise within 30 min. Then, the reaction mass was stirred to 25-30 C for 24 hours. The solid obtained after filtration was stirred in 100 mL of ethanol at 25 C for 1 hour. Finally, the solid obtained was filtered off and dried under vacuum at 50 C.Yield: 5.9 g. Molar yield: 62.89%. HPLC purity: 99.15%. MP.: 189.14 C (DSC).XRD (2Th): 18.0, 20.1 , 21 .6, 23.0, 24.0, 24.1 , 24.3, and 27.6 as shown in figure 5. IR (cm”1): 3473.0, 2912.5, 2691.9, 1745.6, 1661 .6, 1598.7, 1519.5, 1459.3, 1475.5, 1434.8, 1409.9, 1378.0, 1343.0, 1328.9, 131 1.1 , 1288.9, 1263.3, 1227.1 , 1 162.2, 1 136.7, 1 125.3, 1060.4, 1037.9, 1002.6, 982.6, 919.5, 858.4, 833.0, 777.3, 752.5, 710.8, 689.0, 671.8, 597.5, 556.5, 547.3, 526.1 , 516.0, 505.8, 495.9, 486.1 , 475.3, 465.5 and 455.6 as shown in figure 6. Example

According to the analysis of related databases, 446292-08-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; LABORATORIOS LESVI, S. L.; VISHNU NEWADKAR, Ravindranath; CHANGDEO GAIKWAD, Avinash; MADHUKAR HARAD, Ajay; DALMASES BARJOAN, Pere; WO2013/53739; (2013); A1;,
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Electric Literature of 20870-79-5,Some common heterocyclic compound, 20870-79-5, name is 5-Nitroindolin-2-one, molecular formula is C8H6N2O3, 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 mixture of 5-nitroindolin-2-one (15 g, 84 mol)in 1,2-dichioroethane (300 mL) was added POBr3 (23 g,80 mmol) . The mixture was heated to 90C and stirred for0.5 h. Then the reaction was cooled just below 90C andimidazole (6.9 g, 101 mmcl) was added in one portion. The mixture was stirred at 90C for 2 h. The reaction was quenched by ice water (200 mL) and then extracted with DCM (200 mL x 3) . The combined organic phase was washed with brine (300 mL x 2), dried over anhydrousNa2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate=10:1 to 5:1 to 3:1) to give the title compound (11 g, 46 mmol, 54%yield) as a solid.H NMR (400 MHz, DMSO-d6) oe (ppm) 6.86 (s, 1H), 7.49 (d,J=9.2 Hz, 1H) , 7.91 – 8.07 (m, 1H) , 8.50 (s, 1H) , 12.63(br 5, 1H)

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

Reference:
Patent; DAIICHI SANKYO COMPANY, LIMITED; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; NAKAMURA, Tsuyoshi; AKIU, Mayuko; TSUJI, Takashi; TANAKA, Jun; TERAYAMA, Koji; YOKOYAMA, Mika; PINKERTON, Anthony, B.; SESSIONS, Edward, Hampton; (289 pag.)WO2020/10252; (2020); A1;,
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Electric Literature of 954-81-4, These common heterocyclic compound, 954-81-4, name is N-(5-Bromopentyl)phthalimide, 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.

To a stirred solution of compound 14-k (80 g, 0.27 mol) in DMF (745 mL) was added potassium thioacetate (34 g, 0.29 mol) portion wise over 20 min at room temperature. After complete addition, the reaction mixture was stirred at room temperature for 30 min. Reaction progress was monitored by TLC; after completion the reaction mixture was quenched with ice-cold water (1 L) and stirred for 1 h. The resultant precipitate was filtered, washed with water (500 mL) and dried in vacuo to afford 15-k as an off-white solid (75 g, 95%). (1333) 1H NMR (400 MHz, CDC13): delta 7.84 (dd, J= 5.5 Hz, 3.0 Hz, 2H), 7.71 (dd, J= 5.5 Hz, 3.1 Hz, 2H), 3.67 (t, J= 7.3 Hz, 2H), 2.85 (t, J= 7.3 Hz, 2H), 2.30 (s, 3H), 1.73-1.65 (m, 3H), 1.64-1.57 (m, 1H), 1.46-1.37 (m, 2H);LC-MS: 292.2 (M++l).

The synthetic route of 954-81-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CV6 THERAPEUTICS (NI) LIMITED; SPYVEE, Mark; (500 pag.)WO2018/98206; (2018); A1;,
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Some common heterocyclic compound, 41663-84-7, name is 2-Methyl-5-nitroisoindoline-1,3-dione, molecular formula is C9H6N2O4, 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 C9H6N2O4

Example 4. To a reaction vessel were added 4-nitro-N-methylphthalimide (0.51g, 0. 00248 mol), sodium hydrogen sulfide (0.07g, 0.00125 mol), biphenyl (0.204g, 0.00132 mol), triethylamine (0.2 ml, 0.0014 mol), tetrabutylphosphonium bromide (0.15g, 0.00044 mol) and dry toluene (40 ml). The reaction mixture was allowed to proceed at reflux (approximately 145C) for 18 hours. The reaction mixture was sampled and tested by HPLC which indicated a yield of 4,4′-bis(N-methylphthalimide)sulfide of 10% (0.04g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 41663-84-7, its application will become more common.

Reference:
Patent; GENERAL ELECTRIC COMPANY; EP172298; (1991); B1;,
Indoline – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 32692-19-6, name is 5-Nitroindoline, 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 32692-19-6, COA of Formula: C8H8N2O2

A suspension of 5-nitroindoline (6) (1.0 g, 6.09 mmol) in toluene (20 mL) was treated with 2-chloroacetyl chloride (0.97 mL, 12.18 mmol) and heated at 110 C for 15 min. ;The reaction was cooled to room temperature, treated with sat. ;NaHCO3 solution and extracted into ethyl acetate. ;The combined organic layer was dried (Na2SO4) and concentrated. ;The crude was purified by flash column chromatography (EtOAc:hexanes, 1:9 to 1:1 then 2 M NH3 MeOH: ;CH2Cl2, 1:9) to obtain the title compound (1.08 g, 74%). ;1H NMR (CDCl3) delta 8.30-8.27 (m, 1H), 8.14 (dd, 1H, J = 2.1, 9.0 Hz), 8.06 (s, 1H), 4.30 (t, 2H, J = 8.7 Hz), 4.18 (s, 2H), 3.33 (t, 2H, J = 8.4 Hz); ESI-MS (m/z, %): 241, 243 (MH+).

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:
Article; Annedi, Subhash C.; Maddaford, Shawn P.; Ramnauth, Jailall; Renton, Paul; Rybak, Taras; Silverman, Sarah; Rakhit, Suman; Mladenova, Gabriela; Dove, Peter; Andrews, John S.; Zhang, Dongqin; Porreca, Frank; European Journal of Medicinal Chemistry; vol. 55; (2012); p. 94 – 107,14;; ; Article; Annedi, Subhash C.; Maddaford, Shawn P.; Ramnauth, Jailall; Renton, Paul; Rybak, Taras; Silverman, Sarah; Rakhit, Suman; Mladenova, Gabriela; Dove, Peter; Andrews, John S.; Zhang, Dongqin; Porreca, Frank; European Journal of Medicinal Chemistry; vol. 55; (2012); p. 94 – 107;,
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