Category: indolines-derivatives

Reference of 1254319-51-1,Some common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, 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 solution of 6-bromo-2-methylisoindolin-1-one (10.1 g) in THE (250 mL) was addedLDA (33.5 mL, 2 M in THE) at -20C. The mixture was stirred at 0C for 30 minutes andthen methyl 2-bromoacetate (10.3 g) was added at 0C. The mixture was allowed towarm to RT and stirred for 20 hours. The mixture was poured into water (300 mL) and then extracted with EA (200 mL x 3). The combined organic phases were washed with brine (50 mL) and dried over Na2504. After filtration and evaporation of the solvent, the obtained residue was purified by column chromatography on silica gel eluting with ENPE = 1:3 to provide the title compound. MS ESI: mlz = 298 [M+H].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Bromo-2-methylisoindolin-1-one, its application will become more common.

Reference:
Patent; SANOFI; SCHWINK, Lothar; BUNING, Christian; GLOMBIK, Heiner; GOSSEL, Matthias; KADEREIT, Dieter; HALLAND, Nis; LOHMANN, Matthias; POeVERLEIN, Christoph; RITTER, Kurt; WO2015/150565; (2015); A1;,
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Electric Literature of 118289-55-7, These common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)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.

(iii) Preparation of 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one : Charge 1.0 litre demin water, 100 gm of step (ii) product, 122.4 gm 3-(1-piperazinyl)-1,2-benzisothiazole HCl] and 138.2 gm of sodium carbonate into a 3 litre three neck flask at 25 to 30C. Stir for 15 mins and heat to reflux temperature 95 to 100C. Maintain at reflux temperature for 15 hrs. Cool the reaction mixture to 45-50C. Add 1.0 lt of demin water into the reaction mixture and stir for 30 mins. Filter at 45 to 50C and wash with demin water. Suck dry for 30 mins to yield crude product. Charge 2 lt of demin water and above crude product and heat the mixture gradually to 45 to 50C and stir for 30 mins. Filter the product at 45 to 50C and wash with demin water. Suck dry the product for 30 mins. Charge 2.0 lt of demin water and 300 gm of crude product into a 1.0 litre three neck flask at 25 to 30C and heat the mixture gradually to 45 to 50C. Stir for 30 mins. Filter the product at 45 to 50C and wash with demin water till about neutral pH (6.5 to 7.0). Suck dry the product for 30 mins to get wet crude base [5-[2- [4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one. Add 300 gms of wet crude base and 1.0 lt of isopropanol at 25 to 30C. Warm the reaction mixture to 50 to [55C] and stir for 1.0 hr. Cool the reaction mixture gradually to 10 to 15C and stir for 30 mins. Filter the product and wash with chilled isopropanol. Suck dry for 30 mins. Charge 300 gm of wet crude base and 6 lt of tetrahydrofuran (THF). Heat the reaction mixture gradually to reflux temperature 65- 70C. Reflux till clear solution. Cool to 50 to 55C and add charcoal and stir for 30 min at 50 to 55C. Filter the charcoal and wash with hot THF. Distill out THF at 50 to 55C under vacuum till residual volume is 1 lt and cool the reaction mixture gradually to 5 to 10C and stir for 1 hr. Filter the product and wash with chilled THF. Suck dry the product for 30 mins. Dry the product at 60 to 65C.

Statistics shows that 6-Chloro-5-(2-chloroethyl)indolin-2-one is playing an increasingly important role. we look forward to future research findings about 118289-55-7.

Reference:
Patent; SUN PHARMACEUTICAL INDUSTRIES LIMITED; WO2003/99198; (2003); A2;,
Indoline – Wikipedia,
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Synthetic Route of 14192-26-8, These common heterocyclic compound, 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, 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.

(Roth GJ, et al. J Med Chem.2009;52(14):4466-4480). Indolinone 1 (1000 mg, 52.3 mmol) was suspended in acetic anhydride (10 mL) and refluxed at 130 oC for 8 h. The reaction mixture was allowed to cool to 50 oC and (triethoxymethyl)benzene (2930 mg, 131 mmol) was added. The resulting reaction mixture was stirred at 120 oC for 6 h. Then, volatiles were removed in vacuo and petroleum ether was added to the obtained residue. After triturating for 15 minutes, the separated solids were filtered and washed with petroleum ether and then dried under vacuum to afford 974 mg (51%) of title compound.1H NMR (400 MHz, DMSO-d6): delta 8.75 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.49-7.58 (m, 5H), 4.01 (q, J = 7.2 Hz, 2H), 3.87 (s, 3H), 2.44 (s, 3H), 1.35 (t, J = 8.0 Hz, 3H). HRMS m/z found 365.1260, calcd for C21H19NO5 [M]+ 365.1263.

Statistics shows that Methyl 2-oxoindoline-6-carboxylate is playing an increasingly important role. we look forward to future research findings about 14192-26-8.

Reference:
Patent; BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM; DALBY, Kevin N.; EDUPUGANTI, Ramakrishna; TALIAFERRO, Juliana; LEE, Juhyeon; (0 pag.)WO2018/160967; (2018); 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 1677-48-1 as follows. Application In Synthesis of 5,6-Dichloroindoline-2,3-dione

General procedure: A mixture of 4-(chlorobenzyloxy)benzoylhydrazines (0.01 mol) and 4,5-dichloroindolin-2,3-diones (0.01 mol) in ethanol (70 ml) containing 3-4 drops of glacial acetic acid was refluxed for 1-2 hr and left overnight at room temperature. The solid product so obtained was filtered, washed with methanol and recrystallised from aq. DMF. Compounds 1b-5b were synthesized using same method and gave satisfactory analysis for C, H and N.

According to the analysis of related databases, 1677-48-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Harrison, Darwin Anil; Rastogi, Nisheeth; Rahman, Masihur; Indian Journal of Heterocyclic Chemistry; vol. 23; 4; (2014); p. 411 – 418;,
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18711-15-4, name is 4,6-Dichloroisatin, 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. Quality Control of 4,6-Dichloroisatin

1.8 g of Grignard magnesium are placed in 19 ml of anhydrous ethyl ether in a round-bottomed flask equipped with a mechanical stirrer, and under a stream of nitrogen. A mixture of 8.9 ml of 4-bromotrifluoromethylbenzene in 46 ml of anhydrous ethyl ether is then added. The mixture is stirred for one hour, followed by addition of a solution of 5.7 g of 4,6-dichloro-1H-indole-2,3-dione in 100 ml of anhydrous THF. The mixture is stirred at room temperature for 4 hours 30 minutes. Water is added and the resulting mixture is extracted with ethyl acetate. The organic phase is separated out and dried over Na2SO4, filtered and evaporated under vacuum. The residue is taken up in ethyl acetate and washed with 1N sodium hydroxide solution. The organic phase is dried over Na2SO4, filtered and evaporated under vacuum. The solid is taken up in ethyl ether and filtered off. 4.7 g of expected product are obtained.

The synthetic route of 18711-15-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SANOFI-AVENTIS; US2010/210662; (2010); 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. 3416-57-7, name is 2-(2-Oxopropyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C11H9NO3

Compounds 19 and 20 were synthesized by a method similar to that illustrated in paragraph [0313] above except that the starting compound was 2-(2-oxopropyl)isoindoline- 1,3-dione. [0340] Synthesis of 3-((l,3-Diphenyl-lH-pyrazol-5-yl)amino)isonicotinic acid

According to the analysis of related databases, 3416-57-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; EPIZYME, INC.; CAMPBELL, John Emmerson; (178 pag.)WO2016/44666; (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. 16800-68-3, name is 1-Acetylindolin-3-one, A new synthetic method of this compound is introduced below., Computed Properties of C10H9NO2

The N- acetyl-3-indolyl-one 1.75g (10mmol), N- methyl-5-bromo – indole 2.08g (10mmol) and copper triflate 0.18g (0.5mmol) was dissolved in 1, 1,2-dichloroethane, heated to 120 degrees C, the reaction after 16 hours, extracted with methylene chloride, the organic layers combined, dried over anhydrous sodium sulfate, methylene chloride / methanol to give a white solid product N- acetyl-3 – (of N- -3-methyl-5-bromoindole) – indole 3.37g, yield 92%

The synthetic route of 16800-68-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sun Yat-sen University; Weng, Jiang; Lu, Gui; Guo, Jing; (7 pag.)CN105669516; (2016); A;,
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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. 6780-38-7, name is 2-(1,3-Dioxoisoindolin-2-yl)acetyl chloride, A new synthetic method of this compound is introduced below., Formula: C10H6ClNO3

To a solution of phthalylglycyl chloride (6.46 g, 28.9 mmol) in CH2Cl2 (80 mL) was added beta-phenylethylamine (3.55 mL, 28.2 mmol) and triethylamine (7.61 mL, 56.4 mmol). The solution was stirred at room temperature for 1.5 h. To the solution was added 30 mL of water and extracted with CH2Cl2 (2*40 mL). The organic layer was dried over MgSO4 and the solvent was evaporated under reduced pressure. The crude product was purified by crystallization from 50 mL of MeOH to afford the amide as a white solid (8.20 g 94%). 1H NMR (300 MHz, CDCl3) delta 7.90-7.85 (m, 2H), 7.78-7.74 (m, 2H), 7.27-7.15 (m, 5H), 5.69 (br t, 1H), 4.29 (s, 2H), 3.54 (q, 2H), 2.82 (t, 2H); MS (ESI) m/z 309.1 (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; National Health Research Institutes; Ueng, Shau-Hua; Yeh, Shiu-Hwa; Chao, Po-Kuan; Shih, Chuan; (53 pag.)US2019/77786; (2019); A1;,
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Related Products of 3676-85-5, A common heterocyclic compound, 3676-85-5, name is 5-Aminoisoindoline-1,3-dione, molecular formula is C8H6N2O2, 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 1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)piperidine-3-carboxylic acid (500 mg, 1.26 mmol), 5-aminoisoindoline-1,3-dione (250 mg, 1.51 mmol) and pyridine (10 mL) was stirred at 0 C. for 2 h. POCl3 (20 drops) was added and stirred for 10 mins, then water (5 mL) was added and the mixture extracted with ethyl acetate (10 mL). The organic layer was washed with brine (10 mL), then dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by prep-HPLC (Gemini 5u C18 150¡Á21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% TFA, v/v) in a linear fashion over 9 min) to give the product. HCl (1 mL) was added and then the mixture concentrated in vacuo to give 1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(1,3-dioxoisoindolin-5-yl)piperidine-3-carboxamide hydrochloride (10 mg, 2%). 1H NMR (300 MHz, DMSO): delta 11.23 (s, 1H), 10.65 (s, 1H), 10.21 (s, 1H), 8.15 (s, 2H), 7.98 (s, 1H), 7.86 (d, 1H, J=8.4 Hz), 7.77 (d, 1H, J=7.8 Hz), 7.43 (d, 1H, J=8.1 Hz), 6.93 (d, 1H, J=8.1 Hz), 4.29 (d, 1H, J=11.7 Hz), 4.14 (d, 1H, J=12.3 Hz), 3.91 (s, 3H), 7.56 (s, 3H), 3.23-3.02 (m, 2H), 2.73 (s, 1H), 2.10-2.06 (s, 1H), 1.82-1.75 (m, 3H). LC-MS: [M+H]+, 543, tR=1.406 min, HPLC: 98.08% at 214 nm, 98.69% at 254 nm, tR=5.25 min.

The synthetic route of 3676-85-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hoffmann-La Roche Inc.; Hermann, Johannes Cornelius; Kuglstatter, Andreas; Lucas, Matthew C.; Padilla, Fernando; Wanner, Jutta; Zhang, Xiaohu; US2013/109661; (2013); A1;,
Indoline – Wikipedia,
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Some common heterocyclic compound, 317-20-4, name is 7-Fluoroisatin, molecular formula is C8H4FNO2, 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. HPLC of Formula: C8H4FNO2

General procedure: To a pyrex reaction vessel containing a solution of isatin 1a (147 mg, 1.0 mmoL) and NaAuCl4.2H2O (7.95 mg, 2 mol%) in EtOH (1 mL) was added 4-hydroxycoumarin 2 (324 mg, 2.0 mmoL). The resulting mixture was stirred at 40 C for 15 min under microwave irradiation (power level of 200 W). After completion of the reaction as evidenced by TLC, the mixture was cooled to room temperature and poured into ice-cold water (10 mL). The solid obtained was collected by filtration and washed with copious amount of cold water and dried under vacuum at 40 oC for 15 min to afford 251 mg of analytically pure product 3a.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 317-20-4, its application will become more common.

Reference:
Article; Parthasarathy; Praveen, Chandrasekar; Jeyaveeran; Prince; Bioorganic and Medicinal Chemistry Letters; vol. 26; 17; (2016); p. 4310 – 4317;,
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