Category: indolines-derivatives

Electric Literature of 24566-79-8,Some common heterocyclic compound, 24566-79-8, name is N-(6-Bromohexyl)phthalimide, molecular formula is C14H16BrNO2, 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: 2-(omega-Bromoalkyl)-isoindoline-1,3-dione (1 equiv) with N-methylbenzylamine (1 equiv) or its substituted analog in the presence of K2CO3 (3 equiv) was stirred in acetonitrile under reflux for 16 h. Once the reaction was finished, the solvent was evaporated under vacuum, producing a residue that was further dissolved in 50 mL of 5 M NaOH and extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (dichloromethane to dichloromethane/methanol 98:2), yielding a yellow oil. The final product was obtained in the form of hydrochloride salt. The following compounds were obtained.

The synthetic route of 24566-79-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Guzior, Natalia; Bajda, Marek; Rakoczy, Jurand; Brus, Boris; Gobec, Stanislav; Malawska, Barbara; Bioorganic and Medicinal Chemistry; vol. 23; 7; (2015); p. 1629 – 1637;,
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Application of 5394-18-3, 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. 5394-18-3, name is 2-(4-Bromobutyl)isoindoline-1,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: To a suspension of the corresponding secondary amine (3.22 mmol) and anhydrous K2CO3 (765 mg, 5.48 mmol) in CH3CN (20 mL) was added the intermediates 3-5 (0.60 mmol). The mixture was refluxed for 6-8 h. The solvent was removed under reduced pressure. The residue was diluted with water (30 mL) and the mixture was extracted with dichloromethane (30 mL×3). The combined organic phases were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified on a silica gel chromatography in petroleum ether/acetone (20/1, v/v) to afford compound 7-9

The synthetic route of 2-(4-Bromobutyl)isoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Article; Song, Qing; Li, Yan; Cao, Zhongcheng; Qiang, Xiaoming; Tan, Zhenghuai; Deng, Yong; Bioorganic Chemistry; vol. 84; (2019); p. 137 – 149;,
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Reference of 3335-98-6,Some common heterocyclic compound, 3335-98-6, name is 1-Phenyloxindole, molecular formula is C14H11NO, 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.

Example 1Preparation of Compound 1 Sodium hydride (50% dispersion in mineral oil, 0.235 g, 4.8 mmol) was added to a stirred solution of 1,3-dihydro-1-phenyl-2H-indol-2-one 1a (2.0 g, 9.6 mmol) in dimethylacetamide (25 mL). To the resulting solution was added bis(2-chloroethyl)amine (1.7 g, 9.6 mmol) in benzene (25 mL) at room temperature. The resulting reaction was heated to about 50 C. and allowed to stir at this temperature for 0.5 hours, then additional sodium hydride (0.235 g, 4.8 mmol) was added and stirring was continued for 2 hours. The reaction mixture was cooled to room temperature, diluted with benzene and treated with water. The organic phase was dried over MgSO4, filtered and concentrated in vacuo to provide compound 1b.

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

Reference:
Patent; McCormick, Kevin D.; Aslanian, Robert G.; Mangiaracina, Pietro; Berlin, Michael Y.; De Lera Ruiz, Manuel; Boyce, Christopher W.; Chao, Jianhua; Ting, Pauline C.; Zheng, Junying; Rosenblum, Stuart B.; US2011/166124; (2011); A1;,
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Electric Literature of 50727-04-3, 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. 50727-04-3, name is 5-Methoxyisoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of 4-methoxyphthalic anhydride (27.8 g, 0.16 mol) and formamide (175 ml) was stirred and held at 2100C for 5 hours and was then allowed to cool to room temperature overnight. The solid material was filtered off, washed sequentially with water (100 ml), 50% aqueous acetone (50 ml) and diethyl ether (200 ml) and sucked dry under reduced pressure to afford A- methoxyphthalimide (21.3 g, 77%) as a pale yellow solid. 1H NMR (DMSOd6) 11.15 (1 H, br s), 7.74 (1 H, d), 7.33-7.28 (2H, m), 3.92 (3H, s). A stirred solution of 4-methoxyphthalimide (21.3 g, 0.12 mol) in anhydrous tetrahydrofuran (425 ml) at O0C was treated dropwise with a solution of borane in tetrahydrofuran (1M, 340 ml, 0.34 mol) and the resulting mixture was stirred and held at reflux for 16 hours. The mixture was cooled to O0C, methanol (150 ml) was added dropwise followed by 5M hydrochloric acid (150 ml) and the mixture was stirred and held at reflux for 3 hours. Upon cooling to room temperature the organic solvent was removed in vacuo, the mixture was diluted with water (750 ml) and was extracted with dichloromethane (3 x 750 ml). The aqueous layer was basified to pH 12 or above by the addition of 5M sodium hydroxide, extracted with dichloromethane (3 x 750 ml) and the combined extracts were evaporated to dryness in vacuo to afford 5-methoxyisoindoline (8.34 g, 47%) as a brown oil. 1H NMR (DMSO-CJ6) 7.13 (1H, d), 6.84 (1H, d), 6.74 (1H, dd), 4.05 (2H1 s), 4.01 (2H, s), 3.73 (3H, s). MS: [M+H]+ 150.

The chemical industry reduces the impact on the environment during synthesis 5-Methoxyisoindoline-1,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2008/44054; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 6341-92-0,Some common heterocyclic compound, 6341-92-0, name is 6-Chloroisatin, 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.

General procedure: Target compounds 3 were prepared by coupling compounds 1 or 2 with hydrazine hydrate under a mild condition. A mixture of isatin or an N1-substituted isatin (10 mmol) and hydrazine hydrate (5 mmol) was refluxed in ethanol (50 mL) in the presence of acetic acid as the catalyst for 0.5-2 h. After completion of the reaction (monitored by TLC), the solvent was removed under reduced pressure and the crude product was washed with water and recrystallized from ethanol to give pure products (Table 1). Some compounds synthesized in the current study are known compounds and their physicochemical characteristics are consistent with those reported in earlier literature.

The synthetic route of 6341-92-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Liang, Chengyuan; Xia, Juan; Lei, Dong; Li, Xiang; Yao, Qizheng; Gao, Jing; European Journal of Medicinal Chemistry; vol. 74; (2014); p. 742 – 750;,
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Electric Literature of 667463-64-1, The chemical industry reduces the impact on the environment during synthesis 667463-64-1, name is 6-Bromo-1-methylindoline-2,3-dione, I believe this compound will play a more active role in future production and life.

1-3.1 (397 mg, 1.65 mmol) and hydrazine hydrate (1 mL, 20.6 mmol) are heated to 100 C for 1 h and at 125 C for 1 h. To the cool reaction mixture DCM and water are added and the aqueous layer extracted twice with DCM. The combined organic layers are washed with brine, dried, concentrated and the residue purified via column chromatography (using solvent mixture cyclohexane / EA = 3:1). Yield 65%. m/z 226 [M+H]+, m/z 224 [M+H]-, rt 0.58 min, LC-MS Method b.

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-Bromo-1-methylindoline-2,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; GRUNDL, Marc; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; RIETHER, Doris; WIENEN, Wolfgang; WO2013/41497; (2013); 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. 61-70-1, name is 1-Methylindolin-2-one, A new synthetic method of this compound is introduced below., Application In Synthesis of 1-Methylindolin-2-one

General procedure: All reactions were conducted in 10 mL glass vials fitted with crimpcap septum caps. The reaction vial, equipped with a magnetic stir bar,was charged under an N2 atmosphere with 1-methylindolin-2-one (4)(73.6 mg, 0.5 mmol), Pd2(dba)3 (10 mg, 0.011 mmol, 2.5 mol%), i-Pr-BI-DIME (7) (0.022 mmol, 5 mol%), LiHMDS (1 M in toluene, 0.55 mL,0.55 mmol) and the aryl halide (1.1 equiv), then sealed with a crimpcap septum. THF (0.5 mL) and toluene (0.5 mL) were added via syringe and the reaction was heated to 70 C for 4-24 h. The reaction mixture was cooled to room temperature then filtered through a Celite pad with EtOAc (5 mL) as eluent. The filtered solution waswashed with H2O (3 mL), dried over MgSO4 and then concentrated under reduced pressure. The crude residue was purified using a 12 g silica column (30% EtOAc/hexanes) to afford the corresponding oxindole product.

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; Mangunuru, Hari P. R.; Malapit, Christian A.; Haddad, Nizar; Reeves, Jonathan T.; Qu, Bo; Rodriguez, Sonia; Lee, Heewon; Yee, Nathan K.; Song, Jinhua J.; Busacca, Carl A.; Senanayake, Chris H.; Synthesis; vol. 50; 22; (2018); p. 4435 – 4443;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 104618-32-8, name is 2-(4-Oxocyclohexyl)isoindoline-1,3-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. Formula: C14H13NO3

Preparation of 2-amino-6-phthalimido-4,5,6,7-tetrahydrobenzothiazole via 4-(phthalimido)-cyclohexanone; 1.0 Kg of 4-(phthalimido)-cyclohexanol was added in 20.0 L of acetone at 250C to 350C. The reaction mixture was cooled to 50C to 100C and treated with chromic acid solution. 0.2 L of isopropanol was added and stirred for 30 min. The reaction mixture was filtered and washed with acetone (1.0 L). The filtrate was treated with 0.4 kg sodium bicarbonate at 250C to 350C and stirred for 1 h. The reaction mass was again filtered, washed with acetone (1.0 L). Excess of acetone was distilled under vacuum. The residue was treated with 0.5 L ethanol followed by distillation of ethanol under vacuum. The reaction mass was cooled and treated with 3.36 L ethanol at 450C to 250C while gradual cooling. The reaction mixture was further cooled to 150C to 200C and treated with 0.22 L of bromine and 0.43 Kg of thiourea under stirring for 1 h. The reaction mixture was heated to reflux at 750C to 780C for 6 hrs. The reaction mixture was cooled and stirred for 1 hr at 50C to 100C. The product was isolated by centrifuge, washing with ethanol 0.66 L and drying under vacuum at 500C to 550C. (yield: 0.70 Kg).

The synthetic route of 2-(4-Oxocyclohexyl)isoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CADILA HEALTHCARE LIMITED; WO2008/41240; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 5428-09-1, 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 5428-09-1 as follows.

Example 7-2 Preparation of 2-(4-(trimethylsilyl)but-2-en-1-yl)isoindoline-1,3-dione 12 To a solution of 2-allylisoindoline-1,3-dione 11 (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 °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 * 200 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, 78.9 percent) as a yellow resin. Rf: 0.57 (Cyclohexane/EtOAc = 85:15) 1H NMR (300 MHz, CDCl3) delta = -0.10 – 0.09 (m, 9H), 1.44 (d, J = 8.2 Hz, 1.6 H), 1.72 (d, J = 8.8 Hz, 0.4 H), 4.21 (d, J = 6.5 Hz, 1.6 H), 4.29 (dd, J = 14.5, 5.9 Hz, 0.4 H), 5.26 – 5.47 (m, 0.8 H), 5.56 – 5.70 (m, 0.2 H), 5.70 – 5.87 (m, 0.8 H), 5.94 – 6.09 (m, 0.2 H), 7.65 – 7.74 (m, 2H), 7.79 – 7.88 (m, 2H). 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.

According to the analysis of related databases, 5428-09-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V.; The designation of the inventor has not yet been filed; EP2899192; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 22190-33-6,Some common heterocyclic compound, 22190-33-6, name is 5-Bromoindoline, molecular formula is C8H8BrN, 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.

Procedure A: To a mixture of 5-bromoindoline (10.0 g, 50.8 mmol) in DCM (80 mL), was added a solution of di-tert-butyl dicarbonate (11.2 g, 51.3mmol) in DCM (20 mL). The reaction mixture was stirred at RT for 2 h and concentrated in vacuo to give tert-butyl 5- bromoindoline-1-carboxylate as a yellow oil (18.0 g, quantitative yield). LC-MS (ESI): m/z (M)+ = 297.12 / 299.33

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

Reference:
Patent; REMEDY PLAN, INC.; CRIMMINS, Gregory, Thomas; DE JESUS DIAZ, Dennise, Alexandra; BHURRUTH-ALCOR, Yushma; (483 pag.)WO2019/213570; (2019); A1;,
Indoline – Wikipedia,
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