Author: Jessica.F

Reference of 32372-82-0, These common heterocyclic compound, 32372-82-0, name is Isoindoline hydrochloride, 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 stirred suspension of 4- (3-piperidin-1-ylpropoxy) benzoic acid hydrochloride (D2 (Method B); 25g) in DCM (250ML) at rt was treated with oxalyl chloride (10. 92MOL) and 10% DMF in DCM (1 drop). After 2h the solution was evaporated and then re- evaporated from DCM (100ML) and toluene (100ML). The acid chloride was redissolved in DCM (400MOI) and treated with isoindoline hydrochloride (12.8g). The stirred mixture was cooled in ice and triethylamine (46. 4ml) was added over 20min. The mixture was allowed to gain rt and stirred for 1 h. The solution was washed with saturated sodium hydrogen carbonate solution (2#200ML), water (2#200ML), brine (200MI), dried (MGS04) and evaporated. The residue was chromatographed on a silica gel flash column [step gradient 5-9% MEOH (containing 10%. 880 ammonia solution) in DCM]. Fractions containing the required product were evaporated and then re-evaporated from EtOH to give a solid (27.5g) which was redissolved in DCM (300ML), treated with 4M HCI in dioxan (28. 3ML) and then evaporated. The resulting solid was crystallised from EtOH/ diethyl ether to give 2 crops (28.5g). This material was recrystallised from MEOH/ diethyl ether to give the title compound (E2) (26.4g).

Statistics shows that Isoindoline hydrochloride is playing an increasingly important role. we look forward to future research findings about 32372-82-0.

Reference:
Patent; GLAXO GROUP LIMITED; WO2004/37788; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 50727-04-3, These common heterocyclic compound, 50727-04-3, name is 5-Methoxyisoindoline-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.

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 (DMSOd6) 7.13 (1 H, d), 6.84 (1H, d), 6.74 (1H, dd), 4.05 (2H, s), 4.01 (2H, s), 3.73 (3H, s). MS: [M+H]+ 150.

The synthetic route of 50727-04-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2008/44041; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

17702-83-9, name is 2-(8-Bromooctyl)isoindoline-1,3-dione, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: 2-(8-Bromooctyl)isoindoline-1,3-dione

General procedure: To a solution of compound 4 (2 mmol) in N,N-dimethylformamide (DMF) (40.0 mL), the intermediate 2 (0.44 g, 2.5 mmol) and KHCO3 (0.40 g, 4.0 mmol) were added. The mixture was heated at 35-40C for 10 h. Monitored by TLC, and then filtered, concentrated by vacuum. The crude compound was purified by column chromatography on silica gel (VEtOAc-VPet = 2 : 3) to give compound 5. (Chart 1). The 1H-NMR data of compounds 5a-i were listed as follow.

The synthetic route of 17702-83-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Xie, Ruliang; Mei, Xiangdong; Ning, Jun; Chemical and Pharmaceutical Bulletin; vol. 67; 4; (2019); p. 345 – 350;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 7699-18-5, name is 5-Methoxyindolin-2-one, 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. Quality Control of 5-Methoxyindolin-2-one

General procedure: To a Schlenk tube were added indolin-2-one 1 (0.3 mmol), t-BuOOH (0.6 mmol), and DCE (2 mL). Then the tube was stirred at 85 oC under air for the indicated time until complete consumption of starting material monitored by TLC analysis. After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with ethyl acetate (3¡Á10 mL). The combined organic extracts were dried over Na2SO4, removal of the solvent under vacuum afforded the crude product, which was purified further by column chromatography using hexane-ethyl acetate (10:1).

The synthetic route of 5-Methoxyindolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Article; Ying, Wei-Wei; Zhu, Wen-Ming; Liang, Hongze; Wei, Wen-Ting; Synlett; vol. 29; 2; (2018); p. 215 – 218;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 2058-72-2,Some common heterocyclic compound, 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-dione, molecular formula is C9H6BrNO2, 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: A septum-capped vial with a stirring bar was charged with the corresponding isatin(0.1 mmol), ester (0.2 mmol, 2.0 equiv.), catalyst and solvent (1 mL). The reactionmixture was conducted in setting temperature and monitored by TLC. The resultingreaction mixture was vapored in vacuum and the residue was purified by columnchromatography (Hexane/EtOAc = 8/1 to 4/1). The desired products were obtained ascolorless oil or white solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-1-methylindoline-2,3-dione, its application will become more common.

Reference:
Article; Zhang, Xianhui; Zhou, Li; Mahmood, Qaiser; Zhao, Mengmeng; Wang, Xiaowu; Wang, Qinggang; Synlett; vol. 30; 5; (2019); p. 573 – 576;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 169037-23-4, A common heterocyclic compound, 169037-23-4, name is 5-(Trifluoromethoxy)indoline-2,3-dione, molecular formula is C9H4F3NO3, 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.

General procedure: 1M solution of phenylmagnesium bromide in THF (20.40mL, 20.40mmol) was added dropwise to a stirred ice-cold solution of isatin (1g, 6.80mmol) in anhydrous THF (20mL) that was kept under nitrogen. The reaction was stirred at room temperature for 2h and then quenched with a saturated aqueous solution of NH4Cl (20mL). Water was then added (30mL) and the aqueous phase was extracted twice with dichloromethane (2¡Á60mL). The organic phase was washed with brine and dried over anhydrous Na2SO4. The solvent was removed in vacuum and the crude was purified by crystallization from EtOAc/Hexane to afford 1 (1.18g, 77.1%) as a white powder.

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; Denoyelle, Severine; Chen, Ting; Yang, Hongwei; Chen, Limo; Zhang, Yingzhen; Halperin, Jose A.; Aktas, Bertal H.; Chorev, Michael; European Journal of Medicinal Chemistry; vol. 69; (2013); p. 537 – 553;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 114041-16-6, 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 114041-16-6 as follows.

A solution of 5,6-dimethoxyisoindoline 10e (0.08 g, 0.46 mmol) in acetic acid (0.92 mL) is stirred at room temperature. Sulfuryl chloride (0.11 mL, 1.4 mmol) is added drop-wise, and the resulting mixture is stirred at room temperature for 4 h. The reaction is concentrated under reduced pressure to give compound 10k as its HCl salt (0.130 g, quantitative yield) as a light-brown foam, m/z=248/250/252 [M+H]+.

According to the analysis of related databases, 114041-16-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Gladius Pharmaceuticals, Inc.; SUTTON, Larry D.; ZAMBONI, Robert; BUREAU, Patrick; HASSANPOUR, Avid; MAMANI LAPARRA, Laura; VIDAL, Marc; WOO, Simon; ZHOU, Nancy; KEENAN, Richard M.; (127 pag.)US2019/100534; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 4702-13-0, These common heterocyclic compound, 4702-13-0, name is N-Phthaloylglycine, 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.

To a solution of N-Phthaloylglycine (10.0 g, 48.7 mmol) in DCM (100 mL) was added oxalyl chloride (6.3 mL, 73.1 mmol) at r.t., followed by a drop of DMF. The reaction was stirred for 2 h and then concentrated to give compound 651 (10.8 g) as a yellow solid.

Statistics shows that N-Phthaloylglycine is playing an increasingly important role. we look forward to future research findings about 4702-13-0.

Reference:
Patent; HANGZHOU DAC BIOTECH CO. LTD; ZHAO, Robert Yongxin; YANG, Qingliang; HUANG, Yuanyuan; ZHAO, Linyao; GAI, Shun; YE, Hangbo; LEI, Jun; XU, Yifang; CAO, Mingjun; GUO, Huihui; JIA, Junxiang; TONG, Qianqian; LI, Wenjun; ZHOU, Xiaomai; XIE, Hongsheng; BAI, Lu; CAI, Xiang; ZHUO, Xiaotao; ZHANG, Xiuzheng; ZHENG, Jun; (424 pag.)WO2019/127607; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 88150-75-8, name is Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate, 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. Quality Control of Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate

EXAMPLE 1 Ethyl 2-(o-chlorobenzylidene)-4-(2-phthalimidoethoxy)acetoacetate (Compound 3a) 300 g of ethyl 4-(2-(phthalimido)ethoxy)acetoacetate was mixed with 90 ml of 2-chlorobenzaldehyde and 140 ml of 2-propanol. The solution was agitated at 20-25 C. and the solution of 3.6 ml of piperidine in 40 ml of 2-propanol was added dropwise during 2 hours. The mixture was than stirred for 1 hour at the same temperature and 2 hours at 35-40 C. The mixture was acidified with 4.1 ml of acetic acid, 500 ml of 2-propanol was added and the solution was cooled to 0-5 C. Two layers are formed in the reaction mixture; the upper one was separated and the lower organic layer was again washed with 200 ml of 2-propanol. The organic layer, containing the desired product, was evaporated to dryness in order to remove the residual solvent. Yield: 350 g (84%), as the mixture of cis and trans isomers (6:4). Content of 2-chlorobenzaldehyde less than 5%.

The synthetic route of Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Peters, Theodorus H. A.; Benneker, Franciscus B. G.; Slanina, Pavel; Bartl, Jiri; US2002/143046; (2002); A1;; ; Patent; Synthon BV; US6653481; (2003); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-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. category: indolines-derivatives

General procedure: At the first, a mixture containing (10% mol) aimin base ligand and transition metal salts (10% mol) was prepared in 10 ml dichloromethan. Then a mixture of isatin derivatives (1 mmol) and (S)-proline (1.1 mmol), in 10 mL ethanol was added to mixture. After completion of the reaction (monitored by TLC), the reaction mixture was extracted with dichloromethane (15 mL). The combined organic layer dried over anhydrous MgSO4. The organic layer was concentrated in vacuum to furnish the products, which were recrystallized from ethanol.

The synthetic route of 5-Bromo-1-methylindoline-2,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Article; Taghizadeh, Mohammad Javad; Javidan, Abdollah; Jadidi, Khosrow; Journal of the Korean Chemical Society; vol. 59; 3; (2015); p. 205 – 208;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem