Author: Jessica.F

Electric Literature of 264916-06-5,Some common heterocyclic compound, 264916-06-5, name is tert-Butyl 5-aminoisoindoline-2-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.

Step-1: Synthesis of tert-butyl 5-((1-(2-(tert-butyl)pyridin-4-yl)-2-isopropyl-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)isoindoline-2-carboxylate To a stirred solution of 1-(2-(tert-butyl)pyridin-4-yl)-2-isopropyl-6-(methylthio)-1,2-dihydro-3H-indazol-3-one (120 mg, 0.34 mmol, 1.0 eq) in (2.0 mL) of toluene was added m-CPBA (91 mg, 0.37, 1.1 eq) and allowed to stir at rt for 30 minutes. tert-butyl 5-aminoisoindoline-2-carboxylate (102 mg, 408 mmol, 1.2 eq) and DIPEA (0.30 mL, 1.7 mmol, 5.0 eq) were added and allowed to stir at rt for overnight. After completion of reaction, the reaction mixture was diluted with water and extracted with EtOAc (50 mL*2). The combined organic layer was washed with water (50 mL), brine solution (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude product, which was purified by flash chromatography to afford the desired product, tert-butyl 5-((1-(2-(tert-butyl)pyridin-4-yl)-2-isopropyl-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)isoindoline-2-carboxylate (40 mg, 21.73%) as brown solid.

The synthetic route of 264916-06-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; giraFpharma LLC; Chakravarty, Sarvajit; PHAM, Son Minh; Kankanala, Jayakanth; AGARWAL, Anil Kumar; PUJALA, Brahmam; SONI, Sanjeev; ARYA, Satish K.; PALVE, Deepak; Gupta, Ashu; KUMAR, Varun; (498 pag.)US2019/106427; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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 5394-18-3 as follows. Computed Properties of C12H12BrNO2

N-(4-Bromobutyl)phthalimide (1.95 g, 6.89 mmol) and sodium iodide (81 mg, 0.537 mmol) were added to a suspension Of K2CO3 (1.64 g, 11.88 mmol) and 1-Boc-piperazine (1.00 g, 5.37 mmol) in acetone (25 mL) and refluxed for 22 h. The reaction mixture was filtered and the solid was washed with acetone (3 x 50 mL). The filtrate was concentrated and the residue purified by column chromatography (hexane:EtOAc, 7:3 to 0:1) to afford 2.08 g (100%) of 58. 1H NMR (500 MHz, CDCl3): delta 7.84 (dd, J = 3.0, 5.4 Hz, 2H), 7.71 (dd, J = 3.0, 5.4 Hz, 2H), 3.71 (t, J = 7.1 Hz, 2H), 3.38-3.43 (m, 4H), 2.32-2.40 (m, 6H), 1.70 (m, 2H), 1.53 (m, 2H), 1.45 (s, 9H); MS (m/z): [M+H]+ 388.4.

According to the analysis of related databases, 5394-18-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MEMORIAL SLOAN-KETTERING CANCER CENTER; CHIOSIS, Gabriela; TALDONE, Tony; RODINA, Anna; PATEL, Pallav; KANG, Yanlong; WO2011/22440; (2011); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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, Formula: C8H8N2O2

Compound II: A mixture of silver sulfate (100 g, 0.32 mol) and iodine (82 g, 0.32 mol) in N,N-dimethylformamide (700 mL) and ethanol (1400 mL) was treated with 5-nitro-2,3-dihydro-1H-indole I (48 g, 0.29 mol). The resulting mixture was stirred at 25 C. for 1.5 h, filtered and the filter pad washed with ethyl acetate. The filtrate was concentrated in vacuo to a volume of approximately 500 mL. This solution was treated with a 1.0 N aqueous sodium thiosulfate solution (100 mL) and a saturated aqueous sodium chloride solution (400 mL). The resulting precipitate was collected by filtration, washed with water and petroleum ether, and dried in vacuo to afford 7-iodo-5-nitro-2,3-dihydro-1H-indole II (83.9 g, 98.9%) as a white solid: 1H NMR (DMSO-d6, 300 MHz) delta 8.18 (d, J=2.20 Hz, 1H), 7.80 (d, J=1.46 Hz, 1H), 7.03 (broad s, 1H), 3.65 (t, J=8.97 Hz, 2H), 3.17 (t, J=8.60 Hz, 2H).

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

Reference:
Patent; Berthel, Steven Joseph; Thakkar, Kshitij Chhabilbhai; US2004/229890; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 239463-85-5, name is (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, 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 239463-85-5, Safety of (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate

To the Butyl acetate solution of N- alkylated indoline derivative obtained in the reaction step, 35mL of butyl acetate and tartaric acid 1.3 g were added and stirred, and then heated to around 80 C andstirred. After confirming that the tartaric acid was dissolved, then cooled toabout 20 C and stirred for 2 hours. The precipitated solid was collected by filtration, and the resulting wet material was dried under reduced pressure in the vicinity of 40 , to obtain N- alkylated indoline derivative tartrate salt4.6g (purity 96.1%, dialkyl body content 0. 38%) (64.7% yield from the indoline derivative tartrate salt) as a white crystalline.

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, (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; TOKUYAMA CORPORATION; SHIMIZU, TOMOHIRO; TANAKA, KENJI; (18 pag.)JP2016/3183; (2016); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 324-03-8, name is 6-Fluoroindoline-2,3-dione, 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 324-03-8, Formula: C8H4FNO2

7.96 g of the crude product of 6-fluoroisatin were added to 55 mE of water followed by the addition of 16.2 g (6 equivalents) of KOR while cooling with ice and stirring for 30 minutes. 9.9 g (1.5 equivalents) of bromoacetophenone were dropped into the resultant suspension while holding the internal temperature of the reaction mixture at 20 C. to 25 C. followed by additionally stirring overnight at room temperature. Afier neutralizing with concentrated hydrochloric acid, the precipitated crystals were filtered out and washed with a small amount of water. Afier adequately drying the resulting crystals, 7OmE of nitrobenzene heated to 120C. to 130C. were added a little at a time followed by further stirring for 1 hour at 140 C. to 150 C. After cooling the reaction mixture to room temperature, the precipitated crystals were washed with chloroform to obtain 5.4 g of 7-fluoro-3-hydroxy-2- methylquinoline.

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; Nippon Soda Co., Ltd.; Shibayama, Kotaro; Kuwahara, Raito; Sato, Motoaki; Nishimura, Satoshi; Shiinoki, Yasuyuki; Yokoyama, Masahiro; Kitamura, Juri; US2014/73792; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 74572-29-5, name is 5-Chloroisoindolin-1-one, molecular formula is C8H6ClNO, 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. name: 5-Chloroisoindolin-1-one

A mixture of 5-chloro-2,3-dihydro-isoindol-1-one (71 mg, 0.43 mmol), 5-iodo-3?,4?,5?,6?- tetrahydro-2?H- [3 ,4?]bipyridinyl- 1 ?-carboxylic acid tert-butyl ester (150 mg, 0.38 mmol) (example 15 [C]), CuT (22 mg, 0.11 mmol), (iS, 2S)-cyclohexane- 1 ,2-diamine (0.03 mL,0.22 mmol) and K3P04 (165 mg, 0.77 mmol) in dioxane (10 mL) was stuffed at 120C for2 hours. The resulting mixture was poured into water (50 mL) and the aqueous was exacted with EtOAc (30 mL, 3x). The combined organic layers were washed with brine, dried over anhy. Na2SO4 and concentrated in vacuo to get a crude product which was purified by column chromatography (EtOAc: PE = 1:1) to afford title compound (100 mg,61%) as a yellow foam. MS: 428.1 (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 74572-29-5, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; AEBI, Johannes; AMREIN, Kurt; CHEN, Wenming; HORNSPERGER, Benoit; KUHN, Bernd; LI, Dongbo; LIU, Yongfu; MAERKI, Hans P.; MARTIN, Rainer E.; MAYWEG, Alexander V.; TAN, Xuefei; WANG, Lisha; WU, Jun; ZHOU, Mingwei; WO2014/191336; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 3416-57-7, These common heterocyclic compound, 3416-57-7, name is 2-(2-Oxopropyl)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.

(0337) A mixture of phthalimidoacetone (140.0 kg, 689.0 mol, 1.0 equiv.) and i-PrOAc (957 kg) is heated to 30-50 C. Bromine (110.1 kg, 689.0 mol, 1.0 equi.) is added to keep the inner temperature at 30-50 C. The reaction mixture is stirred for 6-14 h at 30-50 C. The reaction mixture is cooled to 15-25 C. and stirred at this temperature for 12-18 h. The reaction mixture is transferred to a second reaction vessel and rinsed with i-PrOAc (261 kg). The reaction mixture is heated to 60-70 C. and pre heated (50-70 C.) water (420 kg) is added to the reaction mixture to keep its inner temperature of 50-70 C. The reaction mixture is heated to 65-71 C. and stirred for 10 min at this temperature. The aqueous phase is separated from the organic phase at 65-71 C. Pre-heated (50-70 C.) water (420 kg) is added to the organic phase at 50-70 C. The biphasic mixture is heated to 65-71 C. and stirred for 10 min at this temperature. The aqueous phase is separated from the organic phase at 65-71 C. The organic phase is heated to 70-80 C. and solvent (980 L) is distilled off under vacuum at 70-85 C. The residual product solution is heated to 67-73 C. and seed crystals (200 g) are added. The thin product suspension is stirred at 67-73 C. for 30-120 min before it is cooled to -15 to -5 C. within 120 min and stirred at this temperature for 60-180 min and then filtered. The filter cake is washed with methyl cyclohexane (MCH) (354 kg) and the product is dried at about 60 C. under vacuum for about 2-3 h. The product 2-(4-bromo-3-oxobutyl)-1H-isoindole-1,3(2H)-dione (VI-j) is obtained as a white crystalline solid (153.7 kg, organic purity HPLC: 94.5 area %, yield: 75.3%).

Statistics shows that 2-(2-Oxopropyl)isoindoline-1,3-dione is playing an increasingly important role. we look forward to future research findings about 3416-57-7.

Reference:
Patent; Boehringer Ingelheim International GmbH; DANG, Mai Thi Quynh; HAMPEL, Thomas Armin; KOCH, Sandra; NORDSTROM, Fredrik Lars; REEVES, Jonathan Timothy; REICHEL, Carsten; SCHOERER, Marvin; STANGE, Christian; VOLCHKOV, Ivan N.; Zhong, Li; ZIMMERMANN, Uwe Johannes; (38 pag.)US2018/251427; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 264916-06-5, name is tert-Butyl 5-aminoisoindoline-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 264916-06-5

Step-1: Synthesis of tert-butyl 5-((1-(6-(tert-butyl)pyridin-2-yl)-2-ethyl-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)isoindoline-2-carboxylate To a stirred solution of 1-(6-(tert-butyl)pyridin-2-yl)-2-ethyl-6-(methylthio)-1,2-dihydro-3H-indazol-3-one (200 mg, 0.582 mmol, 1.0 eq) in (2.0 mL) of toluene was added m-CPBA (287 mg, 1.164 mmol, 2.0 eq) and allowed to stir at rt for 30 minutes. tert-butyl 5-aminoisoindoline-2-carboxylate (164 mg, 0.698 mmol, 1.2 eq) and DIPEA (0.40 mL, 2.328 mmol, 4.0 eq) were added and allowed to stir at rt for overnight. The formation of precipitates were observed which were filtered to afford the desired compound tert-butyl 5-((1-(6-(tert-butyl)pyridin-2-yl)-2-ethyl-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)isoindoline-2-carboxylate (135 mg, 43.83%) as brown solid.

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 264916-06-5.

Reference:
Patent; giraFpharma LLC; Chakravarty, Sarvajit; PHAM, Son Minh; Kankanala, Jayakanth; AGARWAL, Anil Kumar; PUJALA, Brahmam; SONI, Sanjeev; ARYA, Satish K.; PALVE, Deepak; Gupta, Ashu; KUMAR, Varun; (498 pag.)US2019/106427; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 56341-37-8, 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. 56341-37-8, name is 6-Chlorooxindole belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Example 59 Preparation of intermediate E/Z-2-[4-chloro-2-(6-chloro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-phenoxy]-2-methyl-propionic acid tert-butyl ester To a mixture of 2-(4-chloro-2-formyl-phenoxy)-2-methyl-propionic acid tert-butyl ester (5.17 g, 17.3 mmol) and 6-chlorooxindole (2.89 g, 17 3 mmol) were anhydrous methanol (100 mL) at room temperature was slowly added piperidine (1.7 mL, 17.3 mmol). The reaction mixture was heated at 70 C. for 0.5 h. Then the mixture was cooled to room temperature and filtered. The precipitate was dried and collected to give E/Z-2-[4-chloro-2-(6-chloro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-phenoxy]-2-methyl-propionic acid tert-butyl ester as a yellow solid (Yield 6.5 g, 84%).

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-Chlorooxindole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Zhang, Jing; Zhang, Zhuming; US2010/210674; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 22190-33-6, name is 5-Bromoindoline, 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 22190-33-6, Quality Control of 5-Bromoindoline

Step A: tert-Butyl 5-bromo-2,3-dihvdro-lH-indole-l-carboxylate To a stirred solution of 5-bromoindoline (320 mg, 1.62 mmol) in THF (8 mL) was added di-tert-butyl dicarbonate (529 mg, 2.42 mmol) and the resulting mixture was stirred at ambient temperature for 18 h. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc – 100:0 to 90:10, to give the title compound.

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; BELL, Ian, M.; ZHAO, Lianyun; FRALEY, Mark; ZHU, Cheng; BIFTU, Tesfaye; BRNARDIC, Edward Joseph; WANG, Cheng; ZARTMAN, C. Blair; GALLICCHIO, Steven; NGUYEN, Diem; CROWLEY, Brendan; POTTEIGER, Craig; (257 pag.)WO2016/22644; (2016); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem