Author: Jessica.F

Some common heterocyclic compound, 923590-95-8, name is 4-Bromoisoindoline hydrochloride, molecular formula is C8H9BrClN, 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. SDS of cas: 923590-95-8

Step 4: 1-t-Butyl 2-methyl (2S,4R)-4-(11(4-bromo-1,3-dthydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboicylate To a solution of (2S,4R)-B0C-4-hydroxyproline methyl ester (126.3 g, 515 mmol) in DMF (960 mL) at 0 C. was added N,N’-carbonyldiimidazole (83.51 g, 515 mmol). The reaction mixture was stirred at room temperature for 3 h. 4-Bromoisoindoline hydrochloride (120 g, 515 mmol) and diisopropylethylamine (96.3 mL, 540 mmol) were added and the reaction mixture heated to 50 C. for 6 h then allowed to cool to room temperature and stirred overnight The reaction mixture was partitioned between EtOAc (3 L) and 10% aqueous KHSO4 (6 L), the aqueous re-extracted with EtOAc (2 L) and the combined organic phases washed with 10% aqueous NaHCO3, brine, dried over Na2SO4 and solvent evaporated to a foam (239 g). LRMS (ESI) m/z 471.0 [(M+14)* ; calcd for C20H20BrN2O6: 471.1].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 923590-95-8, its application will become more common.

Reference:
Patent; Gilead Sciences, Inc.; US2010/160403; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 40314-06-5,Some common heterocyclic compound, 40314-06-5, name is 5-Methylisoindoline-1,3-dione, molecular formula is C9H7NO2, 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.

Intermediate 5-1Preparation of 2-(5-bromo-4-methylpyridin-3-yl)-5-methylisoindolin-1-one Step 1 A mixture of 5-methylisoindoline-1,3-dione (5.00 g, 31.0 mmol) and tin shavings (8.84 g, 74.5 mmol) in acetic acid (30 mL) and concentrated hydrochloric acid (15 mL) was heated at reflux for 3 h. The hot solution was filtered and the residual tin shavings were washed with acetic acid. The filtrate was concentrated and the residue was diluted with DCM (200 mL), and washed with water (20 mL) and brine (20 mL), dried and concentrated. The precipitate which formed during the concentration was collected by filtration and washed with DCM (5 mL) and dried under vacuum to give 5-methylisoindolin-1-one (2.3 g, 50%). 1H NMR (400 MHz, chloroform-d) delta 7.70 (1H, d, J=7.77 Hz), 7.43 (1H, s), 7.35 (1H, d, J=7.77 Hz), 4.46 (2H, s), 2.48 (3H, s). Mass spectrum m/z 148.0 (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 5-Methylisoindoline-1,3-dione, its application will become more common.

Reference:
Patent; Bristol-Myers Squibb Company; US2010/160303; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 181140-34-1, 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. 181140-34-1, name is (R)-(-)-N-(2,3-Epoxypropyl)phthalimide, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: Compounds 3-7 have been synthesized using a procedure originallyreported by Roehrig et al.16 Chiral amine or amino alcohol(0.6 mmol, 1.2 equiv) in 10 mL isopropanol was added to the solutionof (R)-N-(2,3-epoxypropyl)phthalimide (102 mg, 0.50 mmol)in 10 mL of isopropanol at in an ice bath and stirred for 1 h. thenrefluxed for 12 h. The reaction monitored by TLC. Solvent was removed by rotary evaporator under reduced pressure after completionof the reaction.

The chemical industry reduces the impact on the environment during synthesis (R)-(-)-N-(2,3-Epoxypropyl)phthalimide. I believe this compound will play a more active role in future production and life.

Reference:
Article; Karakaplan, Mehmet; Jameel, Basam; Tetrahedron Asymmetry; vol. 27; 14-15; (2016); p. 597 – 602;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 65435-04-3, 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. 65435-04-3, name is 5-(2-Chloroacetyl)indolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A suspension of 9.3 g 5-chloroacetyl-2-oxindole was stirred in 90 mL pyridine at 80-90 C. for 3 hours then cooled to room temperature. The precipitate was collected by vacuum filtration and washed with 20 mL of ethanol. The solid was dissolved in 90 mL of 2.5 N sodium hydroxide and stirred at 70-80 C. for 3 hours. The mixture was cooled to room temperature and acidified to pH 2 with 0.5 N hydrochloric acid. The precipitate was collected by vacuum filtration and washed thoroughly with water to give crude 5-carboxy-2-oxindole as a dark 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, 5-(2-Chloroacetyl)indolin-2-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Sugen, Inc.; US6395734; (2002); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 64483-69-8,Some common heterocyclic compound, 64483-69-8, name is 5-Acetylindolin-2-one, molecular formula is C10H9NO2, 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.

EXAMPLE II 1,5-diacetyl-2-indolinone 48.9 g (0.279 mol) 5-acetyl-2-indolinone are stirred in 400 ml acetic anhydride in an oil bath at 140 C. for 2 h. The starting material dissolves during this time. Then the reaction mixture is left to cool, evaporated down, the precipitate is removed by suction filtering, washed with ether and the product is dried. Yield: 56.0 g (92.4% of theory) Rf=0.41 (silica gel, methylene chloride/methanol 50:1) C12H11NO3 (MW=217.223) Mass spectrum: m/z=216 (M-H)-

The synthetic route of 64483-69-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Boehringer Ingelheim International GmbH; US2005/209302; (2005); A1;,
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. 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, This compound has unique chemical properties. The synthetic route is as follows., name: Potassium 1,3-dioxoisoindolin-2-ide

To a solution of 240 1-(bromomethyl)-4-methylbenzene (5 g, 27 mmol) in 28 DMF (30 mL) was added 242 potassium 1,3-dioxoisoindolin-2-ide (7.51 g, 40.5 mmol). The mixture was stirred at 100 C. for 14 hours. The reaction mixture was concentrated under reduced pressure to remove DMF. The residue was purified by column chromatography (SiO2, petroleum ether:ethyl acetate=0 to 20%) to give 243 2-(4-methylbenzyl)isoindoline-1,3-dione (5.50 g, 81% yield). 1H NMR (chloroform-d 400 MHz) delta 7.85 (d, J=3.2 Hz, 2H), 7.84 (d, J=3.2 Hz, 2H), 7.34 (d, J=7.6 Hz, 2H), 7.13 (d, J=8.0 Hz, 2H), 4.82 (s, 2H), 2.32 (s, 3H).

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; H. Lundbeck A/S; Juhl, Karsten; Jessing, Mikkel; Langgard, Morten; Vital, Paulo Jorge Vieira; Kehler, Jan; Rasmussen, Lars Kyhn; Clementson, Carl Martin Sebastian; Marigo, Mauro; (154 pag.)US2019/194189; (2019); A1;,
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. 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, This compound has unique chemical properties. The synthetic route is as follows., Formula: C10H9Cl2NO

General procedure: Equimolar mixture of 6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one 1 (1.00mol) and the carbonyl compound (4i-x) (1.00mol) was stirred at RT in methanol (10mL) for 2h in presence of potassium carbonate (1.20mol). After completion, the reaction mass was filtered to remove inorganic salt, added methanol (10-20mL) and activated charcoal to the filtrate and stirred for 1hr. The crude product was filtered to remove charcoal, methanol was evaporated and cooled to 0-5C to get crude solid. Recrystallized using aqueous ethanol or methanol (Yield 60-70%).

According to the analysis of related databases, 118289-55-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Meti, Gangadhar Y.; Kamble, Atulkumar A.; Kamble, Ravindra R.; Somagond, Shilpa M.; Devarajegowda; Kumari, Sandhya; Kalthur, Guruprasad; Adiga, Satish K.; European Journal of Medicinal Chemistry; vol. 121; (2016); p. 221 – 231;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 337536-15-9, 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. 337536-15-9, name is 4-Bromoisoindolin-1-one, This compound has unique chemical properties. The synthetic route is as follows.

Example 10 4-{5-[3-chloro-5-(trifluoromethoxy)phenyl]-1-(pyridine-3-yl)-1H-pyrazole-3-yl}-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-1-one Step 4 [0572] In four parallel procedures, four portions of 175 mg (0.42 mmol) of the product from step 3 are each dissolved in 5 ml dioxane and combined with 128 mg (0.50 mmol) of bis-pinakolato-diboron, 123 mg (1.26 mmol) potassium acetate and 21 mg (0.025 mmol) [1,1-bis-(diphenyl-phosphino)ferrocene]-dichloropalladium-dichloro-methane complex. Each reaction mixture is stirred in the microwave for 1 h at 120 C., cooled to RT, combined with 85 mg (0.50 mmol) of the compound from example 22A, 0.42 ml (2 N in water, 0.84 mmol) of a sodium carbonate solution and 17 mg (0.02 mmol) [1,1-bis-(diphenylphosphino)ferrocene]-dichloropalladium-dichloromethane complex and stirred for 2 h at 120 C. The reaction mixtures are combined. The suspension is diluted with acetonitrile, filtered through a Millipore filter and separated by preparative HPLC (solvent: acetonitrile/water gradient). Once the resulting solid has crystallized out of the acetonitrile, this produces 286 mg (36% of theoretical yield) of the title compound. Example 11 4-{5-[3-chloro-5-(trifluoromethoxy)phenyl]-1-(pyridine-3-yl)-1H-pyrazole-3-yl}-2,3-dihydro-1H-isoindole-1-one [0575] [0576] The synthesis of the title compound is performed starting from 100 mg (0.24 mmol) of the product from step 3 of the compound from example 10 in a manner analogous to step 4 of the synthesis of the compound from example 10. Instead of the compound from example 22A, 4-bromo-2,3-dihydroisoindole-1-on (61 mg, 0.29 mmol) is used. This produces 28 mg (24% of theoretical yield, 94% purity) of the title compound. [0577] 1H-NMR (400 MHz, DMSO-d6): delta=4.73 (s, 2H), 7.21 (s, 1H), 7.51-7.60 (m, 2H), 7.61-7.69 (m, 3H), 7.72 (d, 1H), 7.89 (d, 1H), 8.17 (d, 1H), 8.61-8.71 (m, 2H), 8.75 (s, 1H). [0578] LC-MS (Method 3): Rt=1.13 min; MS (ESIpos): m/z=471 [M+H]+.

The chemical industry reduces the impact on the environment during synthesis 4-Bromoisoindolin-1-one. I believe this compound will play a more active role in future production and life.

Reference:
Patent; AICURIS GMBH & CO. KG; Wildum, Steffen; Klenke, Burkhard; Wendt, Astrid; US2015/203500; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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

EXAMPLE 3 2 moles of Piperazine Benzisothiazole hydrochloride, 1 mole of 5-(2-chloroethyl)-6-chlorooxindole in water (20 times based on benzisothiazole) and in the presence of dispersing agent. All the reactants are charged in to the flask and refluxed under nitrogen, under stirring for 12-16 hr. After the completion of the reaction, the reaction mass is cooled to room temperature and the resulting mass is filtered. It is slurried in IPA and then in water and isolated by filtration. The solid is dried at 95-100 C.Yield: 90-92%, Purity 98% (min).

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; ALKEM LABORATORIES LIMITED; US2011/3995; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 334952-09-9, 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. 334952-09-9, name is 2-Oxoindoline-6-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

2-carbonylindolone-6-carboxylic acid (40 g, 0.23 mol) was added to the reaction flask, 200 ml of methanol was added, and the mixture was slowly added dropwise, and the temperature was raised to 60 C by slowly dropping thionyl chloride (32 g, 0.27 mol). The reaction was carried out for 6 hours. After completion of the reaction, the reaction mixture was evaporated to dryness, ground with methanol, filtered and dried to obtain 40 g of 2-carbonylindolone-6-carboxylate in a yield of 93%.

The chemical industry reduces the impact on the environment during synthesis 2-Oxoindoline-6-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; (6 pag.)CN106854173; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem