Month: May 2021

Reference of 959235-95-1, 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. 959235-95-1 name is 6-(Trifluoromethoxy)indoline, 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.

To a solution of 2-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4-chlorophenyl)-2-((3-methoxy-5-(methylsulfonyl)phenyl)amino)acetic acid 5d (1 .07 g, 1 .97 mmol) inDMF (10 mL) were added HATU (1 .12 g, 2.95 mmol), diisopropylethylamine (976 pL, 5.91 mmol) and 6-(trifluoromethoxy)indoline [CAS 959235-95-1] (400 mg, 1 .97 mmol). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water. The precipitate was filtered off, washed with waterand taken up with EtOAc. The organic layer was washed with a 10% solution ofK2003, water, dried over MgSO4, filtered and the solvent was concentrated under reduced pressure to give 2-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4-chlorophenyl)-2-((3-methoxy-5-(methylsulfonyl)phenyl)amino)-1 -(6-(trifluoromethoxy)indolin-1-yl)ethanone 6a (1.36 g). The crude compound wasused without purification in the next reaction step.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-(Trifluoromethoxy)indoline, and friends who are interested can also refer to it.

Synthetic Route of 114041-16-6,Some common heterocyclic compound, 114041-16-6, name is 5,6-Dimethoxyisoindoline, molecular formula is C10H13NO2, 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 e: simultaneous preparation of 1-(5,6-dimethoxyisoindolin-2-yl)-6-[4-(3-trifluoromethyl-phenyl)piperazin-1-yl]hexan-1-one, 1-isoindolin-2-yl-6-[4-(2-cyanophenyl)piperazin-1-yl]hexan-1-one and 1-isoindolin-2-yl-6-[4-(2-methyl-phenyl)piperazin-1-yl]hexan-1-one A mixture of 0.3 mmol of dicyclohexylcarbodiimide and 0.3 mmol of 1-hydroxybenzotriazole is added to a solution of acid (0.3 mmol) in 2 mL of anhydrous N,N-dimethylformamide. The mixture is left whilst stirring for four hours at 70 C. It is then cooled at ambient temperature, filtered in order to eliminate the dicyclohexylurea. Amine (0.2 mmol) is then added, then it is left for twenty hours at ambient temperature. The N,N-dimethylformamide is evaporated out in a vacuum and the crude is taken up by 2 mL of dichloromethane. It is then washed twice with 1 mL of a normal aqueous solution of soda, then with 1 mL of water. The organic phase is dried then concentrated in a vacuum. Starting from 6-[4-(3-trifluoromethyl-phenyl)piperazin-1-yl]hexanoic acid and 5,6-dimethoxyisoindoline, 1-(5,6-dimethoxyisoindolin-2-yl)-6-[4-(3-trifluoromethylphenyl)piperazin-1-yl]hexan-1-one is obtained in this way. Rf: 0.76 dichloromethane/methanol 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 5,6-Dimethoxyisoindoline, its application will become more common.

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. 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Formula: C10H9Cl2NO

Preparation of 5-(2-(4-(l ,2-benzisothiazol-3-yl)-1 -piperazinyl)ethvD-6-chloro-l ,3-dihydro-2H-indol-2-one(Ziprasidone)In a 50 ml 3 necked round bottom flask there were placed 1 gram (4.56 mmol) of 3-piperazinylbenzo[d]isothiazole; 1.25 grams (5.43 mmol) of 6-chloro-5-(2-chloroethyl)indolin-2-one; 50 mg of potassium iodide; 0.82 gram (5.94 mmol) ofpotassium carbonate and 3 ml of sulfolane. The contents of the flask were heated to 95C to 100 C. The reaction was monitored by HPLC. After completion of the reaction, 50ml of DM water was added to the reaction mixture and stirred. The product was filtered off and washed with water and dried to obtain 1.41 grams (75%) of 5-(2-(4-(l,2-benzisothiazol-3-yl)-l-piperazinyl)ethyl)-6-chloro-l,3-dihydro-2H-indol-2-one. The crude product was purified by IPA and/ or THF. The product matched the spectra of a standard NMR and showed the correct retention time by HPLC with 98.0% assay. The melting point of the compound was found to be 218C -220 C, and was found to conform with the melting point of 218 -220 C as disclosed in US. 5,206,366. Example 3Preparation of 5-(2-(4-(‘l,2-benzisothiazol-3-vD-l-piperazinvDethvl)-6-chloro-l,3-dihydro-2H-indol-2-one(Ziprasidone)In glass-lined reactor placed 21.1 Kg (96.34 mole) of 3-piperazinylbenzo [d]isothiazole; 31 kg (134.7 moles) of 6-chloro-5-(2-chloroethyl)indolin-2-one; 1.1 kg ofpotassium iodide; 20.0 kg (111.92 mole) of potassium carbonate and 63.2 lit ofsulfolane. The contents of the flask were initially heated to 75C to 80 C for 2 hrs.Then temperature was raised to 95C to 100 C and stirred till completion of thereaction. After completion of the reaction 210 lit of DM water was added to the reaction mixture and stirred. The product was filtered off and washed with water and dried to obtain 29.75 kg of 5-(2-(4-(l,2-benzisothiazol-3-yl)-l-piperazinyl)ethyl)-6-chloro-l,3-dihydro-2H-indol-2-one (Ziprasidone).

The synthetic route of 118289-55-7 has been constantly updated, and we look forward to future research findings.

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. COA of Formula: C10H13NO2

General procedure: Compound 8 (70.6 mg, 0.24 mmol) and 5,6-dimethoxyisoindoline(68.5 mg, 0.38 mmol) were dissolved in CH3CN (30 mL), followed by addition of K2CO3 (138.8 mg, 1.00 mmol). The mixture was heated under reflux and stirred at 90 C for 6 h. After cooling and filtration, the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography (petroleum ether/ethyl acetate/triethyamine) = 10:10:1, v/v/v) to afford 13(56.8 mg, 59%)

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.

These common heterocyclic compound, 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, 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. Recommanded Product: 102359-00-2

Example 30 COMPOUND IN-022 2-Oxo-3-[5-(2-pyrrolidin-1-yl-ethoxy)-1H-indol-2-ylmethylene]-2,3-dihydro-1H-indole-5-carboxylic acid 2-Oxo-2,3-dihydro-1H-indole-5-carboxylic acid was condensed with 5-(2-pyrrolidin-1-yl-ethoxy)-1H-indole-2-carbaldehyde to give the title compound. 1H-NMR (360 MHz, DMSO-d6) delta 12.74 (s, 1H, NH), 11.42 (br s, 1H, NH), 8.31 (s, 1H), 8.12 (s, 1H), 7.84 (dd, 1H), 7.53 (d, 1H), 7.2 (3, 1H), 7.14 (m, 1H), 7.0 (m, 2H), 4.26 (m, 2H, CH2), 2.94 (m, 2H, CH2), 2.49 (m, under DMSO), 1.67 (m, 4H, 2*CH2). MS-Ve APCI m/z 416.5 [M+-1].

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

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. 89-40-7, name is 5-Nitroisoindoline-1,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Product Details of 89-40-7

In a 250 ml two-necked flask, 40 ml of absolute ethanol and 10 ml of distilled water, 14.56 g (0.26 mol) of iron powder and 1.643 g (0.031 mol) of ammonium chloride were added.10g (0.052mol) of 4-nitrophthalimide was added under stirring without nitrogen protection; the temperature was set at 65 C, and the reaction was about 4 h.TCL shows that the disappearance of the starting point of the reaction is completed; the pH of the solution is adjusted to 9-10 by sodium carbonate, the filter cake is filtered and dried, and extracted with 100 ml of absolute ethanol (85 C) for 3 times.Ethanol distilled under reduced pressure to give a yellow solid 7.5g, yield 89.03%.

The synthetic route of 89-40-7 has been constantly updated, and we look forward to future research findings.

Reference of 7699-18-5, 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. 7699-18-5, name is 5-Methoxyindolin-2-one, This compound has unique chemical properties. The synthetic route is as follows.

Example A lOO. (l R*.2S*V5′-methoxy-l’-methyl-2-(3-(4-(4-methylpiperazin-l- vDphenv?-l H-indazol–v?spirofcvclopropane-U’-indolini^’-one Sigma^^-trifluoroacetateA . 5-methoxy- 1 -methylindolin-2-oneA dry round-bottom flask was charged with NaH (60% wt) (64 mg, 1.61 mmol) and toluene (2.0 mL). The suspension was heated to 100 0C and then 5-methoxyindolin-2- one (250 mg, 1.53 mmol) was added. After 30 min at 100 0C, Me2SO4 (0.16 mL, 1.68 mmol) was added and the temperature maintained at 1000C for 2.5 h. The reaction was cooled to room temperature and the solvent was removed in vacuo. The residue was purified by column chromatography (silica gel, hexanes/EtOAc, 3: 1 to 2:1) to give the product as a beige solid (144mg, 53%); MS ESI 164.1 [M + H]+, calcd for [C9H9NO2 +H]+ 164.07.

The chemical industry reduces the impact on the environment during synthesis 5-Methoxyindolin-2-one. I believe this compound will play a more active role in future production and life.

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 3891-07-4 as follows. name: 2-(2-Hydroxyethyl)isoindoline-1,3-dione

Into the reaction tank, put 350 kg of toluene, stirring temperature, distillation of toluene, after the liquid in the water separator is filled, keep the reflux water for 60 minutes, and take a sample to measure the water, when the water content of the reflux liquid is ?0.2%, the reflux is changed to distillation, distilled 45kg of toluene (worked ethyl 4-chloroacetoacetate as a dilution solvent), stirring and lowering the temperature, when the temperature in the tank drops to 45 C, the reaction tank is filled with nitrogen, continue to cool down at-5 C, under stirring add 40 kg of N-(2-hydroxyethyl)-phthalimide, and the add 20 kg of sodium hydride, after the addition, cover the can lid, stirring at -5 C, into the metering tank draw 38.4 kg of ethyl 4-chloroacetoacetate, 45 kg of toluene and mix well, at -5 C condition added the drops of ethyl 4-chloroacetoacetate toluene solution, the dropping time is controlled at 4 hours, after the addition, the reaction is stirred and the temperature is slowly increased, the temperature of the reaction solution is slowly raised at 32 C within 5 hours, the reaction time is more than 12 hours, and the temperature is raised at 45 C to continue the heat preservation, until the reaction is complete, cool down, control the internal temperature of 25 C, add 61 kg of glacial acetic acid, after the addition, continue stirring to make the material in the reaction solution stir evenly, and the internal temperature is controlled at 25 C, add 180kg of water, add, continue to stir for 30 minutes, stop nitrogen filling, stop stirring, let stand, divide the water layer into the barrel and transfer the toluene layer to the washing tank, transfer the water layer into the reaction tank, into the reaction tank add 75kg of toluene, stir and let stand, the water layer is separated into barrels, and the toluene layer is transferred to a washing tank, the water layer is transferred into the reaction tank, 75 kg of toluene is added into the reaction tank, stirred, and allowed to stand, and the water layer was separated, combine the toluene layer into a water wash tank, add 100kg of 25% salt water to the washing tank, stir for 15 minutes, let stand for 30 minutes, and separate the water layer, obtained 4-[(2-phthalimido) ethyoxyl] ethyl acetoacetate toluene solution

According to the analysis of related databases, 3891-07-4, the application of this compound in the production field has become more and more popular.

Electric Literature of 675109-26-9, 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. 675109-26-9 name is 6-Bromoisoindolin-1-one, 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.

Example 265: (S)-3-Oxo-N-((4-(trifluoromethyl)phenyl)(3-(trifluoromethyl)- pyridin-2-yl)methyl)isoindoline-5-carboxamide To a 25 mL round bottom flask containing (S)-(4-(trifluoromethyl)- phenyl)(3 -(trifiuoromethyl)pyridin-2-yl)methanamine hydrochloride (Intermediate 1) (120 mg, 0.336 mmol) was added toluene (3 mL). The resulting mixture was stirred at rt for 2 min. At this time,sodium carbonate (143 mg, 1.346 mmol), 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (3.89 mg, 6.73 muiotaetaomicron), palladium (II) acetate (1.5 mg, 6.7 muiotaetaomicron) and 6-bromo-2,3-dihydro-isoindol-l-one (71.3 mg, 0.336 mmol) were added to the flask. The reaction vessel was flushed with argon and then left under 1.0 atm of carbon monoxide gas (from a lecture bottle, in hood). The flask was heated to 85 C overnight, filtered though Celite brnad filter agent, and eluted with EtOAc. Purification by reverse phase HPLC, and concentration of the containing fractions gave (S)-3-oxo-N-((4-(trifiuoromethyl)- phenyl)(3-(trifiuoromethyl)pyridin-2-yl)methyl)isoindoline-5-carboxamide as a yellow foamy solid. 1H NMR (300MHz , CDC13): delta ppm 8.92 (d, J = 4.5 Hz, 1H), 8.40 (d, J = 7.7 Hz, 1 H), 7.60 – 7.56 (m, 5 H), 7.46 – 7.48 (m, 2 H), 6.90 (d, J = 7.6 Hz, 1 H), 4.54 (s, 2 H). MS 480.1 (M+H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromoisoindolin-1-one, and friends who are interested can also refer to it.

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. 550-44-7, name is 2-Methylisoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., name: 2-Methylisoindoline-1,3-dione

ZrCl4 (8.7 g, 37.3 mmol) was added slowly to a solution of 2-methylisoindoline-1,3- dione (41.1, 3.0 g, 18.6 mmol) in THF (50 mL) at -20 C. The mixture was stirred at -20 C for 1h. MeMgBr (1 M, 111.6 mL, 111.6 mmol) was added slowly to the reaction at -20 C. The mixture was stirred at room temperature overnight. The reaction mixture was poured into 5N NaOH solution (while keeping pH 14) and extracted with DCM. The organic solution was concentrated to afford 1,1,2,3,3-pentamethylisoindoline (41.2) as a brown oil (1.0 g, 28%).

According to the analysis of related databases, 550-44-7, the application of this compound in the production field has become more and more popular.