Category: indolines-derivatives

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. 141452-01-9, name is Methyl indoline-5-carboxylate, A new synthetic method of this compound is introduced below., HPLC of Formula: C10H11NO2

The indoline-5-carboxylate (177mg, 1.0mmol) was dissolved in pyridine (4mL), and4- (4- (2- (3- (chlorosulfonyl) benzamido) -4,5,6,7-tetrahydro-benzo [b] thiophen-3-carboxamido) phenethyl) benzoate (800mg, 1.26mmol),The reaction was heated to reflux for 18 hours.The reaction solution was diluted with ethyl acetate (80mL),0.1mol / L hydrochloric acid and washed (10mL ¡Á 3).The organic phase was dried over anhydrous sodium sulfate,concentrate.The crude product was purified by silica gel column chromatography (petroleum ether / dichloromethane (v / v) = 1/1) to give a yellow solid 491mg,Yield: 63.2%.

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; Guangdong East Sunshine Pharmaceutical Co., Ltd.; Wang, Xiaojun; Yang, Xinye; Zhou, Pingjian; Yang, Chuanwen; Lin, Jihua; Xiong, Shaohui; Zhang, Yingjun; Xiao, Ying; Wang, Hui; Cao, Shengtian; Wu, Fangyuan; Ouyang, Luo; (74 pag.)CN105524053; (2016); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 20870-78-4, 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. 20870-78-4 name is 5-Bromoindolin-2-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.

5-Bromo-2-oxindole 16 (150 mg, 0.71 mmol), benzeneboronic acid (113 mg, 0.92 mmol), tetrakis(triphenylphosphine)palladium(0) (61 mg, 0.05 mmol) and Natrium carbonate (250 mg, 2.41 mmol) were suspended in toluene (1.5 mL) and ethanol (1.5 mL) and refluxed for 12 h at 100 C. Water was added and extracted 3 times with ethyl acetate. The combined organic layers were wash with 1N hydrochloric acid, brine, dried over MgSO4, filtered and concentrated in vacuum to give 75 mg (51%) as a light brown solid and was used for the next step without further structure determination.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromoindolin-2-one, and friends who are interested can also refer to it.

Reference:
Article; Goering, Stefan; Taymans, Jean-Marc; Baekelandt, Veerle; Schmidt, Boris; Bioorganic and Medicinal Chemistry Letters; vol. 24; 19; (2014); p. 4630 – 4637;,
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. 924304-73-4, name is 4-Chloroisoindoline hydrochloride, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C8H9Cl2N

Compound 26; Step 2: Synthesis of (2S,4R)-1-(tert-butoxycarbonyl)-4-(4-chloroisoindoline-2- carbonyloxy)pyrrolidine-2-carboxylic acid; To a solution of (25″,4lambda)-1-tert-butyI 2-methyl 4-hydroxypyitauolidme-1,2- dicarboxylate (500 mg, 2 04 mmol) in dry THF (6 mL) was added CDI (430 mg, 2 65 mmol) m one portion and the mixture was stirred at rt for 6 h The amine, 4-chloroisomdoline hydrochloride (0 89 g, 4 7 mmol) was then added in portions, followed by slow addition of DIEA (1 07 mL, 6.12 mmol). The reaction was stirred at rt for overnight. The reaction was diluted with 120 mL EtOAc, washed with IN HCl (2 x 50 mL), water and brine (50 mL each), and dried over Na2SO4 and concentrated down to a thick brownish oil The crude was purified by silica chromatography (eluent = hexanes/EtOAc 2 1), giving the ester product, (25,4J?)-1-tert-butyl 2-methyl 4-(4-chloroisoindolme-2-carbonyloxy)pyrrolidine-1,2- dicaiboxylate, as a light pinkish foamy solid (0 79 g, 91 % yield); (25′,4R)-1-(tert-butoxycarbonyl)-4-(4-chloroisoindoIine-2-carbonyloxy)pyrrolidine-2- carboxylic acid; To a solution of (2S,4R)- 1 -tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2- dicarboxylate (0.50 g, 2.04 mmol) in dry THF (6 niL) was added CDI (430 mg, 2.65 mmol) in one portion and the mixture was stirred at rt for 6 h. 4-chloroisoindoline hydrochloride (0.89 g, 4.69 mmol) was then added in portions, followed by slow addition of DIEA (1.07 mL, 6.12 mmol). The reaction was stirred at rt for overnight. The reaction was diluted with 120 mL EtOAc, washed with IN HCl (2 x 50 mL), water and brine (50 mL each), and dried over Na2SC>4 and concentrated down to a thick brownish oil. The crude was purified by silica chromatography (eluent = hexanes/EtOAc 2: 1), giving (2S,4R)-1-tert-butyl 2-methyl 4-(4- chloroisoindoIine-2-carbonyloxy)pyrrolidine-l ,2-dicarboxylate as a light pinkish foamy solid (0.79 g, 91 % yield).

According to the analysis of related databases, 924304-73-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; INTERMUNE, INC.; ARRAY BIOPHARMA; WO2008/141227; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 239463-85-5,Some common heterocyclic compound, 239463-85-5, name is (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, molecular formula is C26H31N3O8, 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.

1. 80L water was added 200L reactor, adding sodium carbonate 6.2Kg stirring to clarify;2. Add ethyl acetate 50L, stirring,10 Kg of 5 – [(2R) -2-aminopropyl] -2,3-dihydro-1- [3- (benzoyloxy) propyl] -1H-indole-7-carbonitrile tartarate was added, Stir for 2 hours;3. Let stand liquid, the aqueous phase was extracted once with 20 L of ethyl acetate, the combined organic phase;The organic phase was washed twice with 15 L of saturated brine and the organic phase was dried over anhydrous sodium sulfate for 4 hours.5. Suction filtration, desiccant was washed with ethyl acetate; the solvent was dried under reduced pressure to give an oil 7Kg,Is 5 – [(2R) -2-aminopropyl] -2,3-dihydro-1- [3- (benzoyloxy) propyl] -1H-indole-7-carbonitrile, 99%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, its application will become more common.

Reference:
Patent; Beijing Tiantaihenghua Pharmaceutical Co., Ltd.; Li Xueqin; Liu Wenhui; (21 pag.)CN106995399; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature 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 solution of 6 g (0.05 mol) of 4-aminophenol in a mixture of 50 mL of water and 15 mL of 32% hydrochloric acid was cooled on an ice bath to 0C. At continuous stirring maintaining the temperature below 5C a solution was added of 4 g (0.055 mol) of sodium nitrite in 15 mL of water. The obtained solution of a diazonium salt was stirred for 40 min. It was then added to a cooled to -5C solution of tin(II) chloride obtained by dissolving 30 g of tin in a mixture of 50 mL of water and 100 mL of 32% hydrochloric acid. After stirring for 2 h to the reaction mixture was added a solution of 0.05 mol of an appropriate isatin in a sufficient amount of 2-propanol, also a solution was added of 6 g (0.07 mol) of sodium acetate in 35 mL of water. The mixture obtained was stirred for 2 h, heated to 50C, and left standing for crystallization. The separated precipitate was filtered off and several times washed with water on the filter. The filtrate was additionally diluted with water, the separated precipitate was filtered off, washed with water on the filter, the precipitates were combined and dried.

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; Murashevich; Nichik; Zamyatina; Toropin; Burmistrov; Russian Journal of Organic Chemistry; vol. 52; 5; (2016); p. 650 – 654; Zh. Org. Khim.; vol. 52; 5; (2016); p. 665 – 669;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 675109-26-9, These common heterocyclic compound, 675109-26-9, name is 6-Bromoisoindolin-1-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.

Preparation 63: 6-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-2,3-dihydro-1 H-isoindol-1 – one (1578) (1579) A stirred mixture of 6-bromo-2,3-dihydro-1 H-isoindol-1 -one (780 mg, 3.68 mmol), (1580) bis(pinacolato)diboron (1.089 g, 4.28 mmol) and potassium acetate (1.26 g, 12.87 mmol) anhydrous 1 ,4-dioxane (12 mL) was degassed with nitrogen for 5 minutes. 1 ,1′- bis(diphenylphosphino)ferrocene-palladium(ll)dichloride dichloromethane complex (150 mg, 0.18 mmol) was then added and the reaction heated under nitrogen at 100C for 16 hours. After cooling to room temperature the mixture was diluted with water and extracted with EtOAc (x3). The combined organic layers were washed with brine, dried over MgS04, filtered and concentrated under vacuum to yield the title compound (1.1 g, 115 %) which was used crude without purification. MS: [M+H]+ = 260.

Statistics shows that 6-Bromoisoindolin-1-one is playing an increasingly important role. we look forward to future research findings about 675109-26-9.

Reference:
Patent; OTSUKA PHARMACEUTICAL CO., LTD.; BERDINI, Valerio; BUCK, Ildiko Maria; DAY, James Edward Harvey; GRIFFITHS-JONES, Charlotte Mary; HEIGHTMAN, Thomas Daniel; HOWARD, Steven; MURRAY, Christopher William; NORTON, David; O’REILLY, Marc; WOOLFORD, Alison Jo-Anne; COOKE, Michael Liam; COUSIN, David; ONIONS, Stuart Thomas; SHANNON, Jonathan Martin; WATTS, John Paul; (867 pag.)WO2017/68412; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 59-48-3,Some common heterocyclic compound, 59-48-3, name is Indolin-2-one, molecular formula is C8H7NO, 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-a: 5-nitroindolin-2-one: To a stirred solution of oxindole (20 g, 150.21 mmol) in 100 mL of concentrated H2S04 at -15C was added fuming HN03 (9.47 g, 150.206 mmol) dropwise and maintained the reaction temperature at -15C. After completion of addition, the mixture was stirred for 30 min and then poured into ice water. A yellow precipitate was formed which was isolated by filtration (13 g, 48%). -NMR (300 MHz, DMSO-ito): delta 11 (s, 1H), 8.2 (d, 1H), 8.1 (s, 1H), 7.0 (d, 1H), 3.6 (s, 2H).

The synthetic route of 59-48-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ORION CORPORATION; UJJINAMATADA, Ravi Kotrabasaiah; HOSAHALLI, Subramanya; SAMAJDAR, Susanta; ABBINENI, Chandrasekhar; WO2015/92118; (2015); 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. 7699-18-5, name is 5-Methoxyindolin-2-one, A new synthetic method of this compound is introduced below., Recommanded Product: 7699-18-5

General procedure: A 50 mL round-bottom flask equipped with a reflux condenser and a magnetic stir bar was charged with indolin-2-one (10.0 mmol), ethanol(10 mL), acetone (7.3 mL, 0.1 mmol, 10.0 equiv), benzylamine(0.33 mL, 3.0 mmol, 0.3 equiv), and acetic acid (0.17 mL, 3.0 mmol,0.3 equiv). Then, the reaction mixture was heated under reflux for 2 h. The precipitation was filtered off and washed with cold PE (10 mL). The obtained product was dried for 30 min and used without further purification.

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; Hu, Wei-Qiang; Xu, Xiu-Hua; Qing, Feng-Ling; Journal of Fluorine Chemistry; vol. 208; (2018); p. 73 – 79;,
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 334952-09-9 as follows. category: indolines-derivatives

Example 39 COMPOUND IN-031 3-[5-(2-Morpholin-4-yl-ethoxy)-1H-indol-2-ylmethylene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid 2-Oxo-2,3-dihydro-1H-indole-6-carboxylic acid was condensed with 5-(2-morpholin-4-yl-ethoxy)-1HH-indole-2-carbaldehyde to give the title compound.

According to the analysis of related databases, 334952-09-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Tang, Peng Cho; Harris, G. Davis; Li, Xiaoyuan; US2002/52369; (2002); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 56341-37-8, These common heterocyclic compound, 56341-37-8, name is 6-Chlorooxindole, 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.

Preparation of 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl] ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one: (i) Preparation of 6-chloro-5-(chloroacetyl)oxindole : charge 250 ml of methylene dichloride and 100 gm of 6-chloro-oxindole in a 3 litre three neck flask under nitrogen atmosphere at 25 to 30C. Cool gradually to 0 to 5C under stirring and charge 199 gm of anhydrous aluminium chloride in portions at 0 to [50c] and stir for 15 min at 0 to 5C. Add 87.6 gm of chloroacetyl chloride slowly at 0 to 5C over 30 mins. Stir at 0 to 5C for 30 mins. Heat the reaction mixture slowly to reflux (40 to 45C)] over 30 mins. Reflux for 12 hrs. On completion of reaction cool the reaction mixture to 25 to 30C, pour into 1 kg ice, 50 ml of conc. HCl and 450 ml of demin water at 0 to 10C under stirring over 30 mins. Stir for 30 mins, filter solid product and wash with demin water. Prepare a slurry of the solids in hexane and suck dry the product. Dry the product at 70 to 75C.

The synthetic route of 56341-37-8 has been constantly updated, and we look forward to future research findings.

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