Author: Jessica.F

Some common heterocyclic compound, 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, molecular formula is C13H16BrNO2, 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: C13H16BrNO2

To a 10OmL 3-neck round bottom flask are added 5-bromo-l,3-dihydro-isoindole-2- carboxylic acid tert-butyl ester (13.42 mmol; 1.0 equiv), Pd(OAc)2 (0.34 mmol; 0.025 equiv), and P(o-tol)3 (0.67 mmol; 0.05 equiv) and the flask is evacuated and purged with N2 three times. DMF (34 mL), methyl acrylate (14.76 mmol; 1.1 equiv), and Et3N (67.1 mmol; 5.0 equiv) are added and the reaction mixture is heated to 130 C for 15 h. The reaction is cooled to room temperature, diluted with Et2O (200 mL), and the organic layer is washed with 10% citric acid, saturated sodium hydrogen carbonate, and brine. The combined organic extracts are dried (MgSO4), filtered, and concentrated to afford the crude product, which is then purified by silica gel chromatography to yield 5-(2-methoxycarbonyl-vinyl)-l,3- dihydro-isoindole-2-carboxylic acid tert-butyl ester as a yellow solid (1.7 g; 42% yield). 1H NMR (400 MHz, CD3OD): delta 7.68 (d, J= 16 Hz, 1 H), 7.53 (m, 2 H), 7.32 (t, J= 8.0 Hz, 1 H), 6.52 (d, J= 16 Hz, 1 H), 4.64 (d, J= 8 Hz, 4 H), 3.78 (s, 3 H), 1.52 (s, 9 H). MS m/z 305.0 (M+l)+

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 201940-08-1, its application will become more common.

Reference:
Patent; NOVARTIS AG; WO2008/76954; (2008); A2;,
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Reference of 15861-23-1, A common heterocyclic compound, 15861-23-1, name is Indoline-5-carbonitrile, molecular formula is C9H8N2, 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 5-cyanoindoline (70 mg, 0.487 mmol) and 2′-formylbiphenyl-2,4-dicarboxylic acid 4-ethyl ester 2-methyl ester (0.512 mmol) in 4 mL DCE was stirred for 10 min followed by addition of sodium triacetoxyborohydride (0.155 g, 1.5 eq.). Stirring was continued at rt overnight under N2. Reaction was quenched by addition of 1M NaOH then extracted 3× with CH2Cl2. Combined extracts were washed with brine, dried over anh. Na2SO4, filtered and evaporated. Flash silica gel chromatography (hexane/ethyl acetate 85:15) provided the product (0.164 g, 76%) as a white, sticky foam. 1H NMR (CDCl3, 300 mHz) delta 8.58 (s, 1H), 8.14 (d, 1H, J=8.4 Hz), 7.36-7.30 (m, 4H), 7.18-7.13 (m, 4H), 6.00 (d, 1H, J=8.4 Hz), 4.44 (q, 2H, J=7.3 Hz), 4.07 (m, 2H), 3.64 (s, 3H), 3.29 (m, 2H), 2.90 (m, 2H), 1.44 (t, 3H, J=7.3 Hz). LRMS (API+) m/z 441.2 (M+H)+ [100].

The synthetic route of 15861-23-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Smallheer, Joanne M.; Quan, Mimi L.; Wang, Shuaige; Bisacchi, Gregory S.; US2004/220206; (2004); 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. 7699-18-5, name is 5-Methoxyindolin-2-one, A new synthetic method of this compound is introduced below., name: 5-Methoxyindolin-2-one

5-Methoxyisatin (5.0 g) and 30 mL hydrazine hydrate were heated to reflux for 15 minutes. The reaction mixture was cooled to room temperature and 50 mL water was added. The mixture was extracted 3 times with 25 mL of ethyl acetate, the organic layers were combined, dried over anhydrous sodium sulfate and concentrated to give a yellow solid. The solid was stirred in ethyl acetate and 1.1 g of insoluble material removed by vacuum filtration and saved. This material proved to be 2-hydrazino-carbonylmethyl-4-anisidine. The filtrate was concentrated and chromatographed on silica gel eluding with ethyl acetate:hexane 1:1 to give 0.7 g of 5-methoxy-2-oxindole as a dirty yellow solid.

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; Sugen, Inc.; US6878733; (2005); B1;,
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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. 6341-92-0, name is 6-Chloroisatin belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of 6-Chloroisatin

153.8 mg (0.85 mmol) 6-chloroisatin, 102.1 mg (1.02 mmol) 2,4-pentanedione, 50 mL toluene and 5 mL DMF as solvent, 13.6 mg KMnO4 and 7.5 mg MnO2, and 20 mg strong acid ion exchange resin D001 as catalyst were added to a 100 mL round flask. The mixture was stirred and heated at 115 C. for 9 hours. The reaction was monitored with TLC. When TLC indicated that reaction was complete, heating was removed. The reaction mixture was concentrated, filtered, and washed with toluene to obtain 127.2 mg desired product (compound 8), a yield of 56.9%. 1H-NMR (300 MHz, DMSO-d6) delta (ppm): 10.87 (1H, s), 7.21 (1H, d), 6.85 (1H, s), 6.73 (1H, d), 2.28 (3H, s), 2.23 (3H, s); 13C-NMR (75 MHz, DMSO-d6) delta (ppm): 165.5, 164.1, 153.5, 136.8, 128.4, 126.3, 121.3, 115.9, 106.3, 92.5, 23.9, 11.8; MS (ESI) for (M+Na)+: 286.0.

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

Reference:
Patent; SHAANXI UNIVERSITY OF SCIENCE AND TECHNOLOGY; Liang, Chengyuan; Tian, Danni; Jia, Minyi; (11 pag.)US10035808; (2018); B1;,
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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. 552330-86-6, name is 5-Bromoisoindolin-1-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. name: 5-Bromoisoindolin-1-one

Step 1: 5-(Ethylthio)isoindolin-1-one (0428) (0429) 5-Bromoisoindolin-1-one (10 g, 47.16 mmol) and sodium ethanethiolate (9.92 g, 117.90 mmol) were mixed together in DMF (100 mL) and the reaction heated to 100 C. for 20 min. The reaction was cooled to room temperature, poured into water (100 mL) and the product extracted with EtOAc (3×200 mL). The combined organic extracts were washed with brine (4×50 mL). LCMS indicated product in the aqueous washings consequently they were combined and extracted with EtOAc (4×50 mL). The organic extracts were combined, dried using a phase separator cartridge and concentrated in vacuo. The solid obtained was dried under high vacuum overnight. 5-(Ethylthio)isoindolin-1-one (8.68 g, 95%) was obtained as a yellow solid. The material was used in the next step without further purification. (0430) LC/MS: m/z=194 [M+H]+. 1H NMR (500 MHz, DMSO-d6) delta 1.27 (t, 3H), 3.06 (q, 2H), 4.33 (s, 2H), 7.36 (dd, 1H), 7.47-7.48 (m, 1H), 7.57 (d, 1H), 8.45 (s, 1H).

The synthetic route of 552330-86-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AstraZeneca AB; NARJES, Frank; OLSSON, Roine Ingemar; VON BERG, Stefan; LEVER, Sarah; (112 pag.)US2017/166527; (2017); A1;,
Indoline – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 13861-75-1, name is Spiro[cyclopropane-1,3′-indolin]-2′-one, 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 13861-75-1, Recommanded Product: 13861-75-1

A. Preparation of 5′-(1-oxopropyl)spiro-[cyclopropane-1,3′-[3H]indol]-2′(1’H)-one A slurry was made from 7.5 ml of dimethylformamide and 45.5 g of anhydrous aluminum chloride. The temperature rose to 40 C. and 2.97 ml of propionyl chloride and 5.43 g of spiro[cyclopropane-1,3′-[3H]-indol]-2′(1’H)-one were added. The mixture was stirred for 2 hours at 70 C. and was slowly poured into a mixture of ice and 50 ml of concentrated hydrochloric acid. After cooling overnight, the resulting precipitate was recovered by filtration. Crystallization from ethyl acetate provided 4.9 grams of the desired subtitle intermediate, m.p. 183-185 C. Analysis for C13 H13 NO2: Calculated: C, 72.54; H, 6.09; N, 6.51; Found: C, 72.47; H, 6.14; N, 6.42.

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:
Patent; Eli Lilly and Company; US4617302; (1986); A;,
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Related Products of 7477-63-6, 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. 7477-63-6, name is 7-Chloroisatin, This compound has unique chemical properties. The synthetic route is as follows.

Weigh rapamycin (0.05mmol), isatin 3k (0.10mmol) and rhodium octanoate dimer(0.0005mmo),They were placed in a reaction flask, 2.0 mL of dry dichloromethane was added, and after stirring at room temperature for 5 minutes,Phenyldiazo 2a (0.10 mmol) was weighed and dissolved in dry dichloromethane (1.0 mL), and slowly added dropwise to the reaction system (about 1 hour), and stirring was continued for half an hour.The solvent was removed by rotary evaporation to give a crude product. The rapamycin analog I-k was obtained by column chromatography (eluent: petroleum ether: ethyl acetate = 1:10 to 1:4).The yield was 79percent.

The chemical industry reduces the impact on the environment during synthesis 7-Chloroisatin. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Ha Yao Cihang Pharmaceutical Co., Ltd.; Changsha Tianci Bio-pharmaceutical Technology Co., Ltd.; Changsha Cihang Pharmaceutical Institute Co., Ltd.; Duan Yanwen; Huang Yong; Qiu Lin; Wen Zhongqing; Su Meng; (38 pag.)CN109776571; (2019); A;,
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Synthetic Route of 446292-08-6, 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.

63.5 g of the compound 6 (0.15 mol) prepared in Example 4-2 was added to the reaction flask, ethanol (1000 mL), 80% hydrazine hydrate (0.825 mmol) was added dropwise at room temperature, then heated to reflux 2h, the reaction mixture was cooled to room temperature, and the solvent was distilled off under reduced pressure. 1000 mL of water was added and the mixture was extracted twice with dichloromethane (500 mL x 2). The dichloromethane phase was dried over anhydrous sodium sulfate and filtered through suction. The filtrate was evaporated to dryness to give a white solid which was dried in vacuo to give compound 7 (45.9 g); the yield was 95.4% and the purity was 99.7%.

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; Shandong Luoxin Pharmaceutical Group Stock Co. Ltd.; Hou, Junkai; Wang, Yuehui; Li, Hua; (12 pag.)CN105801572; (2016); A;,
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Indoline | C8H9N – PubChem

Synthetic Route of 3891-07-4, 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. 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

To a cooled to -10 C. suspension of imidazole (16.3 g, 0.24 mol) and PPh3 (31.5 g, 0.12 mol) in dry CH2Cl2 (160 mL) I2 (30.5 g, 0.12 mol) was added in portions. After the addition the formed suspension was stirred for 30 min at room temperature followed by addition of P1 (15.3 g, 0.08 mol) in portions. The reaction mixture was stirred for 24 h, then aqueous Na2S2O3 was added. Organic layer was consequently washed with water, brine, and dried over Na2SO4. After evaporation yellow-green residue was obtained, which was chromatographed (CH2Cl2/hexanes 1:2) on silica gel. Recrystallization of the final product from hexanes/acetone yielded 20.9 g (87%) of white fibers.

The chemical industry reduces the impact on the environment during synthesis 2-(2-Hydroxyethyl)isoindoline-1,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Koltun, Dmitry; Zablocki, Jeff; Vasilevich, Natalya; Migulin, Vasily; US2009/253693; (2009); A1;,
Indoline – Wikipedia,
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Synthetic Route of 129487-92-9,Some common heterocyclic compound, 129487-92-9, name is tert-Butyl 5-aminoindoline-1-carboxylate, molecular formula is C13H18N2O2, 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.

Part H. To tert-butyl-5-amino-1-indolinecarboxylate (1.90 g, 8.2 mmol) was added 5-bromovaleryl chloride (1.4 mL, 9.0 mmol) and 18 mL of THF. After stirring for 5 min at rt under N2, potassium tert-butoxide (9 mL, 9 mmol; 1.0 M in THF) was added in one portion, and the resulting brown solution was stirred under N2 for 30 min. A second portion of potassium tert-butoxide (9 mL) was added, and the resulting brown suspension was stirred for 15 min. An additional 0.10 mL-portion of 5-bromovaleryl chloride and a 4.5 mL-portion of potassium tert-butoxide were added, and the mixture was stirred for 30 min. The reaction was then poured into H2O (80 mL). The aqueous layer was washed with EtOAc (3*50 mL), and the combined organic layers were washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated and the resulting residue was purified by radial chromatography (50% EtOAc in hexanes) to afford tert-butyl 5-(2-oxo-1-piperidinyl)-1-indolinecarboxylate as a pink solid (1.30 g, 50%). LRMS (AP+): 317.2 (M+H)+. 1H NMR (CDCl3) delta7.40-7.80 (br m, 1H), 7.01 (s, 1H), 6.97 (d, 1H), 3.94 (t, 2H), 3.55 (br m, 2H), 3.09 (t, 2H), 2.49 (br m, 2H), 1.91 (br m, 4 H), 1.52 (s, 9H).

The synthetic route of 129487-92-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pinto, Donald J.P.; Quan, Mimi L.; Orwat, Michael J.; Li, Yun-Long; Han, Wei; Qiao, Jennifer X.; Lam, Patrick Y.S.; Koch, Stephanie L.; US2003/191115; (2003); A1;,
Indoline – Wikipedia,
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