Author: tianli

1914-02-9, 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. 1914-02-9 name is 3,3-Dimethylindoline, 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.

The product is prepared according to the procedure described in example 5, using 177 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, 236 mg of 3,3-dimethylindoline (which can be prepared according to T. W. Ramsay et al., Synth. Commun. 1995, 25, 4029) and 169 mg of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride in a mixture of 0.11 ml of pyridine and 5 ml of N,N-dimethylformamide. The reaction mixture is stirred for 15 h at ambient temperature and then concentrated to dryness under reduced pressure. 40 ml of water are added to the residue and triturated with a spatula at ambient temperature. The precipitate formed is filtered off, and then solubilized with a dichloromethanemethanol mixture and dried. After concentration to dryness under reduced pressure, the crude product is purified by chromatography on a 30 g silica (0.02-0.045 mm) column, eluent: 90/10 v/v dichloromethanemethanol. After the various fractions have been evaporated, the pink solid residue is triturated from 10 ml of diisopropyl ether, filtered off, and then dried under a bell jar (1h40 C./20 mbar). 134 mg of 2-[2-(3,3-dimethyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one are thus obtained in the form of a pink solid

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,3-Dimethylindoline, and friends who are interested can also refer to it.

Reference:
Patent; Sanofi; Cali, Jean – Christophe; Sertar, Victor; Array, Frank; Carlson, Carl Andreas; Shio, Laulan; Thompson, Fabienne; (178 pag.)JP5680638; (2015); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

61-70-1,Some common heterocyclic compound, 61-70-1, name is 1-Methylindolin-2-one, molecular formula is C9H9NO, 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: An oven-dried reflux tube equipped with a magnetic stir bar and a Teflon stopcock was charged with aryl halide (1 mmol), oxindole (1 mmol),potassium carbonate (1.1 mmol), catalyst nanoparticles (0.05 mmol)and 1,4-dioxane (2 ml) and heated at 70 C. The mixture was vigorously stirred under these reaction conditions and completion of the reaction was monitored by TLC (EtOAc: n-hexane, 25:75). After completion of the reaction, the reaction mixture was cooled to room temperature, the magnetic nanoparticles of the catalyst were collected using a magnet. Ethyl acetate (5 mL) and water (10 mL)were added to the mixture in the next step. The aqueous layer was furtherextracted by ethyl acetate (2*5 mL). The combined organic layerswere washed with saturated brine, dried over CaCl2, filtered, and concentrated to give a residue which was purified by recrystallization from ethanol and water or by column chromatography on silica gelusing EtOAc: n-hexane, 1:7.

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

Reference:
Article; Moghaddam, Firouz Matloubi; Tavakoli, Ghazal; Latifi, Fatemeh; Saeednia, Borna; Catalysis Communications; vol. 75; (2016); p. 37 – 41;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

111992-61-1, 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. 111992-61-1 name is 2-(3-Bromo-2,2-dimethylpropyl)isoindoline-1,3-dione, 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.

A mixture of 3 (0.48 g, 1.6 mmol) and NaN3 (0.13 g, 1.9 mmol) in DMF (2 mL) was stirred at 100 C for 8 h. The reaction mixture was poured into H2O (10 mL) and the suspension was extracted with EtOAc (2 ¡Á 10 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification of the residue by flash chromatography (hexane:EtOAc, 20:1) gave 4 (0.39 g, 93%) as a white solid: mp 61-62 C; 1H NMR (300 MHz, CDCl3) delta 1.01 (s, 6H), 3.24 (s, 2H), 3.59 (s, 2H), 7.72-7.88 (m, 4H); 13C NMR (75 MHz, CDCl3) delta 23.7, 38.0, 45.7, 60.8, 123.3, 131.9, 134.1, 168.9; MS (ESI) m/z 281.1 [M+Na]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(3-Bromo-2,2-dimethylpropyl)isoindoline-1,3-dione, and friends who are interested can also refer to it.

Reference:
Article; Wu, Yong; Shi, Chen; Sun, Xiaowei; Wu, Xiaoming; Sun, Hongbin; Bioorganic and Medicinal Chemistry; vol. 19; 14; (2011); p. 4238 – 4249;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

A common heterocyclic compound, 264916-06-5, name is tert-Butyl 5-aminoisoindoline-2-carboxylate, molecular formula is C13H18N2O2, 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. 264916-06-5.

A solution of tert-butyl 5-aminoisoindoline-2-carboxylate (2.000 g, 8.536 mmol) in dichloromethane (50 mL) was mixed at the room temperature with methanesulfonyl chloride (0.661 mL, 8.536 mmol) and triethylamine (1.428 mL, 10.243 mmol), and stilTed at the same temperature for 18 hr. Then, saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The residue was chromatographed (5i02, 40 g cartridge; ethyl acetate / hexane = 20 % to 50 %) to give tert-butyl 5-(methylsulfonamido)isoindoline-2-carboxylate as white solid (2.220 g, 83.3 %).

The synthetic route of tert-Butyl 5-aminoisoindoline-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CHONG KUN DANG PHARMACEUTICAL CORP.; LEE, Jaekwang; HAN, Younghue; KIM, Yuntae; CHOI, Daekyu; MIN, Jaeki; BAE, Miseon; YANG, Hyunmo; KIM, Dohoon; (644 pag.)WO2017/18803; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, 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. 1074-82-4

20ml (1.3X 10 1 mol) 1,6-dibromopentane with 8 g (4.3X 10 2moles) Phthalimide potassium salt dissolved in 100ml of N, N- dimethylformamideand under room temperature it was stirred for 20 hours. The solvent wasdistilled off under reduced pressure The residue using n-hexane: ethyl acetatewith a volume ratio of 10: 1 eluent tocarry out column chromatography, graduallyincreasing the polarity to hexane: ethyl acetate with a volume ratio of 5: 1 togive a product of 9.6g (3.1X102 mole) a bromo group substituted by Phthalimide.The product with 8g (6. 3X 10 2 mol) of sodium sulfite, 160ml waterand 100ml95% ethanol mixed reaction was heated to 100 C for 20h, theremaining solvent was drained, and the resulting residue was mixed with 98ml ofconcentrated hydrochloric acid then was heated to 110 C the for 20H, it was drained,with water – 95% ethanol on the residue to carry out recrystallization to give 3.9g of 6-amino-1-hexylsulfonic acid (totalyield 50%).

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 1074-82-4.

Reference:
Patent; Institute of Chemistry Chinese Academy of Sciences; zhao, jingquan; DENG, HONG; XEI, JIE; (16 pag.)CN101948412; (2016); B;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 1168150-46-6, name is (E)-Methyl 3-(methoxy(phenyl)methylene)-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. 1168150-46-6

General procedure: A mixture of intermediate (3a, 3b, 6a, 6b, 10a, 10b, 11a-d, and14a-g, 1.5 mmol) and methyl (E)-3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate (1.5 mmol) in methanol (10 mL) wasstirred under reflux for 5-10 h. When TLC showed the completionof the reaction, the solution was cooled to room temperature. Theprecipitate was filtered off to give a crude product, which wasrecrystallized from methanol to provide the target compounds.

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 1168150-46-6.

Reference:
Article; Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang; European Journal of Medicinal Chemistry; vol. 139; (2017); p. 492 – 502;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1336963-95-1, 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. 1336963-95-1, name is 6-Bromo-7-fluoroindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 6-bromo-7-fluoroindoline-2,3-dione (1.41 g, 5.80 mmol) in 2 N NaOH (15 mL), H2O2 solution (30%, 3 mL) was added at 0oC and the resulting mixture was stirred at 0oC for 30 minutes. After stirring at room temperature for 16 hours, the mixture was poured into ice-water, and acidified with concentrated HCl. The precipitate was collected by filtration and air dried to afford compound 5-5 (1.2 g, 89% yield) as a white solid.

The synthetic route of 1336963-95-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARAXES PHARMA LLC; LI, Liansheng; FENG, Jun; LONG, Yun, Oliver; LIU, Yuan; REN, Pingda; LIU, Yi; (135 pag.)WO2017/58915; (2017); 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. 39603-24-2, name is 5,7-Dimethylindoline-2,3-dione, A new synthetic method of this compound is introduced below., 39603-24-2

General procedure: To a stirred solution of tetraethyl methylenebis(phosphonate) (0.69 mmol, 200 mg) in anhydrousTHF (10 mL) was added NaH (1.52 mmol, 60 mg) slowly at 0 C. After 10 minutes, a solution ofisatine (0.69 mmol) in anhydrous THF (2 mL) was added. After completion (monitored by TLC),water was added, and the mixture was extracted with ethyl acetate (3 ¡Á 20 mL). The combinedorganic phases were dried with anhydrous Na2SO4 and concentrated under reduced pressure. Theresidue was purified by flash chromatography on silica gel (hexane/ethyl acetate). To a stirredsolution of the above product (0.65 mmol, 182 mg) in anhydrous THF (10 mL) was added DMAP(0.13 mmol) and TEA (0.98 mmol) at 0 C. Then (Boc)2O (0.78 mmol, 170 mg) was added. Aftercompletion, water was added, and the mixture was extracted with ethyl acetate (3 ¡Á 20 mL). Thecombined organic phases were dried with anhydrous Na2SO4 and concentrated under reducedpressure. The residue was purified by flash chromatography on silica gel (hexane/ethyl acetate).

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; Zhou, Qing-Qing; Yuan, Xin; Xiao, You-Cai; Dong, Lin; Chen, Ying-Chun; Tetrahedron; vol. 69; 48; (2013); p. 10369 – 10374;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, molecular formula is C10H9NO3, 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. 14192-26-8

To a suspension of NaH (12.6 g) in THF (260 ml) was added at 22 C methyl 2-oxoindoline-6- carboxylate (15.0 g) over 30 min, which was followed by the addition of Mel (44.5 g) using a syringe-pump over 80 min keeping the temperature between 24 – 28 C and stirring was continued for 2.5 h. A solution of NaOH (6.3 g) in water (20 ml) was added and stirring was continued for 1 h. The mixture was partitioned between water and TBME, the pH of the aqueous layer was adjusted to 1, the suspension was filtered and the residue dried to give the title compound (16.0 g, 93%) as a brown solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 14192-26-8, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; HILPERT, Hans; KOLCZEWSKI, Sabine; LIMBERG, Anja; STOLL, Theodor; WO2015/177110; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

603-62-3, The chemical industry reduces the impact on the environment during synthesis 603-62-3, name is 3-Nitrophthalimide, I believe this compound will play a more active role in future production and life.

3-Nitrophthalimide (LOOGR) was taken into a hydrogenation vessel and dissolved using 500ML of dimethylformamide. Raney nickel catalyst (20gr, wet) was added to the solution and subjected to hydrogenation conditions initially at 20-30C UNDER 20-40psi. After the exothermic nature of the reaction was over, hydrogen pressure was increased to 40-60psi and the temperature to 40-50C. After the hydrogen uptake is over sample was drawn from the reaction mass and checked for the absence of 3-nitrophthalimide by TLC. The reaction mixture was filtered while hot and the catalyst removed by filtration. Solvent was removed from the filtrate under reduced pressure at 60-80C. Water (500ML) was added to the residue and the mixture stirred for 20-30MIN. The product was isolated by filtration and dried at 60-70C to get a yellow crystalline solid of 3-aminophthalimide (80gr, 95%). Melting point: 262-4C.

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

Reference:
Patent; NATCO PHARMA LIMITED; VENKAIAH CHOWDARY, Nannapaneni; WO2004/43919; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem