Month: February 2021

Electric Literature of 118289-55-7, These common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-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.

(iii) Preparation of 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one : Charge 1.0 litre demin water, 100 gm of step (ii) product, 122.4 gm 3-(1-piperazinyl)-1,2-benzisothiazole HCl] and 138.2 gm of sodium carbonate into a 3 litre three neck flask at 25 to 30C. Stir for 15 mins and heat to reflux temperature 95 to 100C. Maintain at reflux temperature for 15 hrs. Cool the reaction mixture to 45-50C. Add 1.0 lt of demin water into the reaction mixture and stir for 30 mins. Filter at 45 to 50C and wash with demin water. Suck dry for 30 mins to yield crude product. Charge 2 lt of demin water and above crude product and heat the mixture gradually to 45 to 50C and stir for 30 mins. Filter the product at 45 to 50C and wash with demin water. Suck dry the product for 30 mins. Charge 2.0 lt of demin water and 300 gm of crude product into a 1.0 litre three neck flask at 25 to 30C and heat the mixture gradually to 45 to 50C. Stir for 30 mins. Filter the product at 45 to 50C and wash with demin water till about neutral pH (6.5 to 7.0). Suck dry the product for 30 mins to get wet crude base [5-[2- [4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one. Add 300 gms of wet crude base and 1.0 lt of isopropanol at 25 to 30C. Warm the reaction mixture to 50 to [55C] and stir for 1.0 hr. Cool the reaction mixture gradually to 10 to 15C and stir for 30 mins. Filter the product and wash with chilled isopropanol. Suck dry for 30 mins. Charge 300 gm of wet crude base and 6 lt of tetrahydrofuran (THF). Heat the reaction mixture gradually to reflux temperature 65- 70C. Reflux till clear solution. Cool to 50 to 55C and add charcoal and stir for 30 min at 50 to 55C. Filter the charcoal and wash with hot THF. Distill out THF at 50 to 55C under vacuum till residual volume is 1 lt and cool the reaction mixture gradually to 5 to 10C and stir for 1 hr. Filter the product and wash with chilled THF. Suck dry the product for 30 mins. Dry the product at 60 to 65C.

Statistics shows that 6-Chloro-5-(2-chloroethyl)indolin-2-one is playing an increasingly important role. we look forward to future research findings about 118289-55-7.

Reference:
Patent; SUN PHARMACEUTICAL INDUSTRIES LIMITED; WO2003/99198; (2003); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 1254319-51-1,Some common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, 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 6-bromo-2-methylisoindolin-1-one (10.1 g) in THE (250 mL) was addedLDA (33.5 mL, 2 M in THE) at -20C. The mixture was stirred at 0C for 30 minutes andthen methyl 2-bromoacetate (10.3 g) was added at 0C. The mixture was allowed towarm to RT and stirred for 20 hours. The mixture was poured into water (300 mL) and then extracted with EA (200 mL x 3). The combined organic phases were washed with brine (50 mL) and dried over Na2504. After filtration and evaporation of the solvent, the obtained residue was purified by column chromatography on silica gel eluting with ENPE = 1:3 to provide the title compound. MS ESI: mlz = 298 [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 6-Bromo-2-methylisoindolin-1-one, its application will become more common.

Reference:
Patent; SANOFI; SCHWINK, Lothar; BUNING, Christian; GLOMBIK, Heiner; GOSSEL, Matthias; KADEREIT, Dieter; HALLAND, Nis; LOHMANN, Matthias; POeVERLEIN, Christoph; RITTER, Kurt; WO2015/150565; (2015); A1;,
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Indoline | C8H9N – PubChem

Related Products of 19727-83-4, 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. 19727-83-4, name is 6-Nitroindoline belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 6-nitroindoline (5.00 g, 30.5 mmol) in CH2C12 (100 mL) was added Et3N (4.25 mL, 3.08 g, 30.5 mmol) and TFAA (4.23 mL, 6.40 g, 30.5 mmol) and the resulting solution stirred at RT for Ih. More Et3N (4.25 mL, 3.08 g, 30.5 mmol) and TFAA (4.23 mL, 6.40 g, 30.5 mmol) were added and the solution was stirred at RT for another 2h. Water (100 mL) was added and the mixture was extracted with CH2C12 (3×100 mL), dried (MgSO4), and concentrated to yield 2,2,2-trifluoro-1-(6-nitroindolin-1- yl)ethanone (8.9 g, crude yield > 100%) as a yellow-brown solid.

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

Reference:
Patent; DECIPHERA PHARMACEUTICALS, LLC; WO2006/71940; (2006); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 3339-73-9, name is 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid, molecular formula is C11H9NO4, 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: 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid

To a solution of 3-(1,3-dioxoisoindolin-2-yl)propanoic acid (300 mg, 1.31 mmol) in dichloromethane (5mL) at r.t. was added thionyl chloride (0.15 mL, 2.06 mmol) and the mixture was heated at reflux for 2h. The mixture was then concentrated by rotary evaporator to afford 3- (1,3-dioxoisoindolin-2-yl)propanoyl chloride, which was used immediately for the next reaction. To asolution of 3-(1,3-dioxoisoindolin-2-yl)propanoyl chloride in dry dichloromethane (5 mL) was added phenothiazine (200 mg, 1 mmol) and pyridine (0.5 mL) at 0 C. After being stirred at r.t. for 5 h, the reaction was quenched by 3 mol¡ÁL-1 hydrochloric acid (10 mL). The organic layer was separated and the aqueous layer extracted with dichloromethane (2 ¡Á 15 mL). The combined organic extracts were washed with saturated NaHCO3, dried with Na2SO4 and rotary evaporated. The crude product was recrystallized from 95% ethanol to afford 6c (380 mg, 95.0%) as white soild, m.p. 256.5-257.5 C. 1H NMR (300 MHz, CDCl3): delta 8.48 (s, 1H), 7.81 (dd, J = 5.4, 3.0 Hz, 2H), 7.69 (dd, J = 5.4, 3.0 Hz, 2H), 7.49 (d, J = 6.6 Hz, 2H), 7.42 (d, J = 7.8 Hz, 2H), 7.31 (t, J = 7.2 Hz, 2H), 7.21 (t, J = 7.5 Hz, 2H). 13C NMR (100 MHz, CDCl3): delta 169.15, 168.03, 138.27, 134.01, 133.92, 132.10, 128.06, 127.11, 126.97, 123.25, 34.28, 32.74. ESI-HRMS m/z calcd. for C23H17N2O3S ([M+H]+) 401.0954, found 401.0960.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3339-73-9, its application will become more common.

Reference:
Article; He, Chun-Xian; Meng, Hui; Zhang, Xiang; Cui, Hua-Qing; Yin, Da-Li; Chinese Chemical Letters; vol. 26; 8; (2015); p. 951 – 954;,
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 868066-91-5 as follows. Formula: C9H8BrNO

In a sealable tube was combined Pd2dba3 (0.0270 g, 0.0295 mmol), 2- (dicyclohexylphosphino) -2′ , 4′, 6′- tri-i-propyl-1, 1′ -biphenyl (0.0563 g, 0.118 mmol) , 4 , 4, 5, 5- tetramethyl-2- (4,4, 5 , 5-tetramethyl-l, 3 , 2-dioxaborolan-2-yl) – 1, 3, 2-dioxaborolane (0.450 g, 1.77 mmol), 5-bromo-2- methylisoindolin-1-one (see Tsuritani, T., et al Synlett 2006, 5 801-803} (0.267 g, 1.18 mmol) , potassium acetate (0.232 g, 2.36 mmol) and 2 mL dioxane . The mixture was blanketed with N2, sealed and heated at 80 C for 22 h. The mixture was allowed to cool to rt then diluted with EtOAc, and the organic layer washed with water, sat. NaHCO3, then dried over Na2SO4, filtered and evaporated. The residue was purified via flash chromatography using a EtOAc in CH2Cl2 gradient. The title compound was collected as a tan solid.

According to the analysis of related databases, 868066-91-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AMGEN INC.; WO2008/8539; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, 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 1074-82-4, Application In Synthesis of Potassium 1,3-dioxoisoindolin-2-ide

Under nitrogen atmosphere, 115g of aluminum chloride was added into 750ml of methylene chloride and the slurry mass was cooled to about 0C. lOOg of cis-(+/-)-l- phenyl-3-oxabicyclo[3.1.0]hexan-2-one, compound of formula VI was added at about 0C and the reaction mixture was stirred for about 30min at about 10C. Then diethyl amine solution (125.8g of diethyl amine in 200ml of methylene chloride) was added to the reaction mixture at about 10C to about 15C over a period of 45min and the reaction mixture was stirred for about 60min at about 10C to about 15C. Then 1800ml of water was added to the reaction mixture at about 10C to about 20C over a period of about 30min and stirred for about 2h at about room temperature. 25g of Hyflo was added and stirred for about lOmin. The reaction mixture was filtered through Hyflo bed and the Hyflo bed was washed with 100ml of methylene chloride. The organic layer was separated and taken into a clean container. The aqueous layer was again extracted with 300ml of methylene chloride; where a second organic layer was obtained. The combination of the organic layers was washed with 500ml of water followed by washing with 500ml of 10% aqueous sodium chloride solution, then the organic layer was treated with 50g of sodium sulphate. The organic layer was taken into a round bottomed flask and was cooled to 15C and 95.75 gm of thionyl chloride was slowly added at about 15C to about 20C over a period of about 30min and the reaction mixture was stirred for about 30min at about 15C to about 20C. The reaction mass was cooled to about 0C and 319g of potassium phthalimide was added, the temperature was raised to about 40C to about 45C and stirred at same temperature for about lh, then the reaction mass was cooled to about 10C to about 15C. Then 2.5 liters of 4% aqueous sodium hydroxide solution was added to the reaction mixture at about 10C to about 20C and stirred for about 30min. The aqueous and organic layers were separated and the organic layer was washed 4 times with 700ml each of water and solvent of the organic layer was distilled out completely under vacuum. 200ml of methanol was added to the residue mass at about 35C to about 40C and stirred for about lOmin. Then methanol was distilled out completely under vacuum. Then, 600ml of methanol was added to the residue mass and the temperature was raised to about 65 C and stirred for about 30min. The reaction mixture was cooled to about 20C to about 25C and stirred for about 2h. The precipitated product was filtered and washed with 100ml of chilled methanol. The wet cake was added to 1500ml of water and the slurry was stirred at about 55C to about 60C for about 2h. The solid was filtered at about the same temperature and washed with 500ml of water. The wet cake was added to 350ml of acetone and heated about reflux temperature, then 5g of activated charcoal was added to the clear solution and maintained reflux for about 30min. The reaction mass was filtered through Hyflo bed and the bed was washed with 30ml of acetone. Slowly the clear solution was cooled to about room temperature over a period of lh. Solid was precipitated out and the slurry was maintained for about lh at about room temperature. The solid was filtered out and washed with 50ml of chilled acetone. The compound was dried at about 50C to about 55C for about 15h to yield 1 lOg of the title compound.Purity by HPLC: 99.2%

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, Potassium 1,3-dioxoisoindolin-2-ide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLENMARK GENERICS LIMITED; JAMBUKAR, Nagambar Genuji; GHARPURE, Milind; SINARE, Sudam Nanabhau; THOMBRE, Pravin Chhaburao; KHAN, Mubeen Ahmed; WO2011/158249; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 129487-92-9, These common heterocyclic compound, 129487-92-9, name is tert-Butyl 5-aminoindoline-1-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.

To a solution of 3-(4-((2-chloropyrimidin-4-yl)amino)-l-oxoisoindolin-2-yl)piperidine- 2,6-dione (50 mg, 0.135 mmol) and tert- butyl 5-aminoindoline-l-carboxylate (32 mg, 0.135 mmol) inlBuOH (2 mL) was added TFA (21 pL, 0.27 mmol), and then the mixture was heated to reflux overnight. The mixture was then concentrated in vacuo and purified by prep-HPLC (MeOHTLO, 0.05% TFA) to obtain compound 43 (10.4 mg, 13%).NMR (500 MHz, DMSO-dis) d 11.01 (s, 1H), 10.48 (d, J= 30.2 Hz, 2H), 8.02 (d, J = 6.9 Hz, 1H), 7.95 (d, J= 7.8 Hz, 1H), 7.66 (dd, J= 7.5, 1.1 Hz, 1H), 7.61 (t, J= 7.6 Hz, 1H), 7.07 (s, 1H), 7.01 (s, 2H), 6.46 (d, J = 6.9 Hz, 1H), 5.15 (dd, 7 = 13.2, 5.1 Hz, 1H), 4.49 (d, J = 17.5 Hz, 1H), 4.34 (d, J = 17.5 Hz, 1H), 3.56 (t, J= 8.2 Hz, 2H), 2.99 (t, J = 8.1 Hz, 2H), 2.94 – 2.85 (m, 1H), 2.64 – 2.55 (m, 1H), 2.33 (ddd, 7 = 26.6, 13.2, 3.2 Hz, 1H), 2.25 (s, 1H), 1.90 (dd, 7 = 11.1, 5.2 Hz, 1H).LCMS (m/z): 470 [M+H]+.

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

Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael; ZHANG, Tinghu; FISCHER, Eric; VERANO, Alyssa; HE, Zhixiang; DU, Guangyan; DONOVAN, Katherine; NOWAK, Radoslaw; YUAN, Christine; (0 pag.)WO2020/6264; (2020); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 446292-07-5, 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. 446292-07-5, name is (R)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)amino)propyl)isoindoline-1,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Add 18.30 g of the white solid, 30.01 g of N, N-carbonyldiimidazole, and 220 ml of tetrahydrofuran to a 500 ml three-necked flask, heat to reflux, and reflux for 4 h. The system was cooled to room temperature, filtered, the solid was washed with 20 ml of tetrahydrofuran, and dried at 60 C. for 8 h to obtain 17.55 g of off-white solid with a yield of 90.0%.

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)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)amino)propyl)isoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Hunan Jiu Dian Pharmaceutical Co., Ltd.; Guo Zhe; Lu Guoyan; Tan Wen; Xiao Wending; (13 pag.)CN110818700; (2020); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 2436-29-5, These common heterocyclic compound, 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal, 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 1-(1-benzyl-5-methyl-1H-benzimidazol-2-yl)-2-methyl-propylamine (0.56 mmol) and 3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionaldehyde (114 mg, 0.56 mmol) in dry DCM (3 mL) at room temperature, was added sodium triacetoxyborohydride (119 mg, 0.56 mmol). After 10 min., acetic acid (34 mul, 0.56 mmol) was added to the reaction mixture. The mixture was stirred at room temperature for 1 h. The solvent was removed in vacuo and the solid was dissolved in ethyl acetate. The organic layer was washed with saturated NaHCO3, dried over MgSO4, filtered and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography to give crude material that was used in step 7.

The synthetic route of 2436-29-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Boyce, Rustum S.; Guo, Hongyan; Mendenhall, Kris G.; Walter, Annette O.; Wang, Weibo; Xia, Yia; US2006/84687; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 118289-55-7,Some common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, molecular formula is C10H9Cl2NO, 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.

3. Preparation of ZPR in water/Na3CO . Na2SO4. In a three necked flask was charged BITP HC1 (lOg), CEI (10.35g) Na2C03 (14.1 g, ), Na2SO4 (40g) and water (50. 7g) and the reaction mixture was heated at reflux for 9 hours. After 9 hours reflux, the ziprasidone peak is No.71% area from the reaction mixture.; 6. Preparation of ZPR in the presence of Na2SO4. In a 250g three necked flask was charged water (25ml), Na2C03 (6.91g), Na2S04 (19.72g), BITP HCl (4.9g) and CEI (4.68g). The mixture was stirred at-100C for 12 hours. The isolated solid weights after drying 7.77g (purity by HPLC 85.15%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Chloro-5-(2-chloroethyl)indolin-2-one, its application will become more common.

Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2005/40160; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem