Category: 496-12-8

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. 496-12-8, name is Isoindoline, A new synthetic method of this compound is introduced below., COA of Formula: C8H9N

To ketone 24 (43 mg, 0.15 mmol) in anhydrous THF/CH2Cl2 (1.5 ml/1.5 mL) is added isoindoline (25 muL, 0.22 mmol) and glacial acidic acid (3 muL) and triacetoxyl sodium borohydride (98 mg, 0.44 mmol). The mixture is stirred for 2 h and, quenched with saturated sodium bicarbonate, and extracted with CH2Cl2. The organic phase is dried, rotavaped, and was subjected to HPLC purification (aetonitrile-water-0.1% TFA) to give the title compound as a TFA salt (67 mg, 89%).1H-NMR (400 MHz, CDCl3) delta=2.2 (4H, m), 2.3 (3H, s), 2.4 (3H, s), 3.2 (2H, m), 3.6 (1H, m), 3.8 (2H, m), 4.5 (4H, bs), 5.1 (2H, bs), 7.3 (9H, m).HR MS (m/z, MH+) meas. 399.2547.

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; Novartis AG; US2010/41663; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 496-12-8, name is Isoindoline, A new synthetic method of this compound is introduced below., COA of Formula: C8H9N

To ketone 24 (43 mg, 0.15 mmol) in anhydrous THF/CH2Cl2 (1.5 ml/1.5 mL) is added isoindoline (25 muL, 0.22 mmol) and glacial acidic acid (3 muL) and triacetoxyl sodium borohydride (98 mg, 0.44 mmol). The mixture is stirred for 2 h and, quenched with saturated sodium bicarbonate, and extracted with CH2Cl2. The organic phase is dried, rotavaped, and was subjected to HPLC purification (aetonitrile-water-0.1% TFA) to give the title compound as a TFA salt (67 mg, 89%).1H-NMR (400 MHz, CDCl3) delta=2.2 (4H, m), 2.3 (3H, s), 2.4 (3H, s), 3.2 (2H, m), 3.6 (1H, m), 3.8 (2H, m), 4.5 (4H, bs), 5.1 (2H, bs), 7.3 (9H, m).HR MS (m/z, MH+) meas. 399.2547.

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; Novartis AG; US2010/41663; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 496-12-8,Some common heterocyclic compound, 496-12-8, name is Isoindoline, molecular formula is C8H9N, 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.

Stage 1: 5-nitro-isoindoline (I-12) A solution of isoindoline (3.9 g, 32.8 mmol, 1.0 eq.) in dichloromethane (20 mL) was stirred below -20 C. with exclusion of moisture while adding dropwise sulphuric acid (98%, 16.0 mL). The 2-layer mixture was allowed to reach 20 C. and then dichloromethane was removed under vacuum. The resulting pale brown solution was stirred and kept below 20 C. while adding nitric acid (70%, 3.9 mL) dropwise. The resulting pale orange-red solution was added with stirring to ice/water (300 mL) and tert-butyl methyl ether (100 mL). Sodium hydrogen carbonate (59 g) was added in portions and finally 4M aqueous sodium hydroxide (10 mL). The layers were separated and the aqueous phase extracted with tert-butyl methyl ether (4*150 mL). The combined organic phases were dried (sodium sulphate) and evaporated giving a red-brown gum (4.6 g, 85%) which was used in the next stage without purification. 1H NMR (250 MHz, CHLOROFORM-d) delta ppm 8.05-8.19 (m, 2H) 7.38 (d, J=8.83 Hz, 1H) 4.32 (s, 4H) 2.14 (br. s., 1H)

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

Reference:
Patent; INTERMUNE, INC.; US2010/119479; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 496-12-8, 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. 496-12-8, name is Isoindoline, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 2,3-dihydro-1 H-isoindole (0.3 mL) in dichloromethane (5 mL)Triethylamine (0.7 mL)And the mixture was ice-cooled to 0 C.,2-Bromoacetyl bromide (0.4 mL) was added dropwise, followed by stirring at room temperature for 18 hours.Water was added to the reaction solution, the mixture was extracted with dichloromethane and washed with saturated brine.The organic layer was dried over sodium sulfate and the solvent was distilled off under reduced pressure to obtain a residue.Purification by silica gel column chromatography (hexane-ethyl acetate)2-Bromo-1- (2,3-dihydro-1 H-isoindol-2-yl)Ethan-1-one281 mg (yield 47%) was obtained.

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

Reference:
Patent; NATIONAL CENTER FOR GERIATRICS AND GERONTOLOGY; YANAGISAWA, KATSUHIKO; KAWAI, AKIYOSHI; (139 pag.)JP2017/171619; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 496-12-8, name is Isoindoline, A new synthetic method of this compound is introduced below., Safety of Isoindoline

methyl 1-(6-chloropyrimidin-4-yl)piperidine-4-carboxylate 15 (500 mg, 1.96mmol), 2,4-difluorophenol (1.02 g, 7.82mmol) and Cs2CO3 (2.56 g, 7.82mmol) were combined in a microwave vial, and NMP (11mL) was added. The resulting solution was heated to 180C with microwave irradiation for 20 min, after which time solids were removed by filtration, and crude residue was purified by RP-HPLC. Fractions containing product were extracted with 3:1 chloroform/IPA. Solvents were dried with MgSO4, filtered and concentrated to give product 16 as a brown, spongy solid (320 mg, 49%). 1H NMR (400MHz, CDCl3) delta 8.27 (s, 1H), 7.20 – 7.14 (m, 1H), 6.97 – 6.88 (m, 2H), 6.05 (s, 1H), 4.27 – 4.24 (m, 2H), 3.17 – 3.10 (m, 2H), 2.70 – 2.63 (m, 1H), 2.06 – 2.02 (m, 2H), 1.82 – 1.73 (m, 2H); 13C NMR (101MHz, CDCl3) delta 179.03, 169.60, 163.87, 161.28, 161.18, 158.82, 158.72, 157.72, 156.01, 155.89, 153.51, 153.38, 136.62, 124.63, 124.54, 111.68, 111.64, 111.45, 111.41, 105.68, 105.46, 105.41, 105.19, 85.88, 43.83, 40.68, 27.46 (multiple Cs coupled to F). LCMS (215nm) RT=0.764 min (>98%); m/z 336.2 [M+H]. Compound 16 (50 mg, 0.15mmol) and isoindoline (0.028mL, 0.22mmol) were dissolved in DMF (2mL), and DIPEA (0.13mL, 0.75mmol) and HATU (85 mg, 0.22mmol) were added. The resulting solution was stirred at r.t. for 1 h, after which time crude residue was purified directly by RP-HPLC. Fractions containing product were basified with sat. NaHCO3, and extracted with 3:1 chloroform/IPA. Organic extracts were filtered through a phase separator and concentrated to give product 17e as a light brown solid (42 mg, 65%). 1H NMR (400MHz, CDCl3) delta 8.26 (s, 1H), 7.32 – 7.27 (m, 4H), 7.20 – 7.14 (m, 1H), 6.96 – 6.87 (m, 2H), 6.09 (s, 1H), 4.93 (s, 2H), 4.82 (s, 2H), 4.48 – 4.41 (m, 2H), 3.10 – 3.03 (m, 2H), 2.83 – 2.75 (m, 1H), 1.93 – 1.88 (m, 4H); 13C NMR (101MHz, CDCl3) delta 173.19, 169.70, 163.99, 161.12, 161.02, 158.67, 158.57, 157.87, 156.02, 155.90, 153.52, 153.39, 136.74, 136.70, 136.62, 136.58, 136.54, 136.01, 128.10, 127.72, 124.64, 124.62, 124.54, 124.52, 123.22, 122.70, 111.55, 111.51, 111.32, 111.29, 105.56, 105.34, 105.29, 105.07, 85.94, 52.51, 52.47, 43.96, 40.47, 27.59 (multiple Cs coupled to F). LCMS (215nm) RT=0.950 min (>98%); m/z 437.2 [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:
Article; Bender, Aaron M.; Weiner, Rebecca L.; Luscombe, Vincent B.; Cho, Hyekyung P.; Niswender, Colleen M.; Engers, Darren W.; Bridges, Thomas M.; Jeffrey Conn; Lindsley, Craig W.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 11; (2017); p. 2479 – 2483;,
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 496-12-8 as follows. HPLC of Formula: C8H9N

General procedure: A solution of N-heterocycle compound (0.2 mmol) and graphene oxide (GO) (8 mg) in N,N-dimethylformamide(1.0 mL) was stirred in a sealed tube under an atmosphere of argon at 150 C for 18 h. After being cooled to room temperature,the reaction mixture was filtered and washed with ethyl acetate (20 mL). Afterward, 10 mL water was added tothe solution and extracted with ethyl acetate (3 × 15 mL), the combined organic layers were dried over anhydrous Na2SO4.The solvent was evaporated under vacuum and the crude product was purified by preparative thin-layer chromatography (TLC) on silica gel with petroleum ether and ethyl acetate to achieve the pure product.

According to the analysis of related databases, 496-12-8, the application of this compound in the production field has become more and more popular.

Reference:
Article; Ma, Juan; Zhang, Jingyu; Zhou, Xiao; Wang, Jiawei; Gong, Hang; Journal of the Iranian Chemical Society; vol. 15; 12; (2018); p. 2851 – 2860;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 496-12-8, A common heterocyclic compound, 496-12-8, name is Isoindoline, molecular formula is C8H9N, 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.

Conc. H2SO4 (8 mL) was added dropwise at 0 C to a solution ofisoindoline (19) (2 g) in DCM (10 mL), and the reaction mixturewasstirred at rt for 10 min. DCM was evaporated under vacuum fromthe reaction mixture and conc. HNO3 (2 mL) was added dropwise at0 C. The reaction mixture was stirred for 2 h at rt. Ice water wasadded to the reaction mixture then the reaction mixture wasbasified with sodium bicarbonate. Extraction was done with EtOAc(100 mL x 3) and the combined organic layer was dried overanhydrous MgSO4 and concentrated under reduced pressure to give 20 in 50% yield; 1H NMR (300 MHz, CDCl3): d 8.07e8.12 (m, 2 H),7.34 (d, J 8.5 Hz, 1H), 4.32 (s, 4H).

The synthetic route of 496-12-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Ojha, Ritu; Nepali, Kunal; Chen, Chun-Han; Chuang, Kuo-Hsiang; Wu, Tung-Yun; Lin, Tony Eight; Hsu, Kai-Cheng; Chao, Min-Wu; Lai, Mei-Jung; Lin, Mei-Hsiang; Huang, Han-Li; Chang, Chao-Di; Pan, Shiow-Lin; Chen, Mei-Chuan; Liou, Jing-Ping; European Journal of Medicinal Chemistry; vol. 190; (2020);,
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. 496-12-8, name is Isoindoline, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of Isoindoline

General procedure: Naphthylboronic acid (0.25 g, 1.5 mmol) was added with 0.094 g of phenol (1.0 mmol) to 15 mL of DCM. Copper(II) acetate (0.36 g, 2.0 mmol) was then added along with triethylamine (0.5g, 5.0 mmol), and the dismembrator horn placed in the reaction vessel. The sonicator was set to 55 watts and the reaction was allowed to proceed for 4 hours (1 minute pulse with a 3 second rest). Post reaction, the product was isolated by column chromatography. Product yields were determined by weight and purity was confirmed by GC/MS and NMR.

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 496-12-8.

Reference:
Article; Musolino, Bryan J.; Kabalka, George W.; Heterocycles; vol. 90; 1; (2015); p. 271 – 297;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 496-12-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 496-12-8 name is Isoindoline, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Preparation of the title compound was initiated by subjecting the product from step 2 A (0.02 g, 0.03 mmol) to isoindoline (0.01 g, 0.06 mmol) andDBU (0.01 g, 0.06 mmol) in 1 mL DCM at 45 0C for 3 h. Once complete byMS analysis, the reaction was diluted with 10 mL EtOAc and extracted withNaHCtheta3 (2 x 10 mL) and brine (2 x 20 mL). The organic phase was dried over anhydrous Na2SO4, filtered, and then concentrated in vacuo. The residue was purified by silica gel flash chromatography using 70%EtOAc/hexanes affording pyridazinone 4a. (0.01 g, 64 %).MS (ESI) m/z = 755.3 (M+H)+.

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

Reference:
Patent; ENANTA PHARMACEUTICALS, INC.; WO2008/19266; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 496-12-8, 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. 496-12-8, name is Isoindoline belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 94 N-[5-(1,3-dihydroisoindol-2-ylcarbonyl)-1-methylpyrrol-3-yl]-4′-trifluoromethylbiphenyl-2-carboxylic Acid Amide Prepared analogously to Example 1d from 4-(4′-trifluoromethylbiphenyl-2-carbonylamino)-1-methylpyrrole-2-carboxylic acid, 2,3-dihydro-1H-isoindole, TBTU and N-ethyldiisopropylamine in dimethylformamide. Yield: 79% of theory; Rf value: 0.64 (silica gel; dichloromethane/ethanol=9:1); C28H22F3N3O2 (489.50); mass spectrum: (M-H)-488; (M+H)+=490; (M+Na)+=512.

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, Isoindoline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Boehringer Ingelheim Pharma KG; US2003/73836; (2003); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem