Category: indolines-derivatives

Adding a certain compound to certain chemical reactions, such as: 883-44-3, name is 2-(3-Hydroxypropyl)isoindoline-1,3-dione, 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 883-44-3, Computed Properties of C11H11NO3

Step 2. Preparation of 3-(l,3-dioxoisoindolin-2-yl)propanal A mixture of 2-(3-hydroxypropyl)isoindoline-l,3-dione (2.0 g, 8.76 mmol) and IBX (8.2 g, 29.27 mmol) in 60 mL EA was refluxed for 2 h. The mixture was filtered and filtrate was concentrated to afford 3-(l,3-dioxoisoindolin-2-yl)propanal (2.0 g , yield: 100%) as white solid. NMR (500 MHz, CDC13): delta 9.82 (s, 2H), 7.84-7.86 (m, 2H), 7.72-7.74 (m, 2H), 4.04 (t, J = 7.0 Hz, 2H), 2.87-2.89 (m, 2H) ppm. MS (ESI): m/z 553.7 [M+l]+.

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, 2-(3-Hydroxypropyl)isoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EPIZYME, INC.; CHESWORTH, Richard; KUNTZ, Kevin, Wayne; OLHAVA, Edward, James; PATANE, Michael, A.; WO2012/82436; (2012); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 141452-01-9,Some common heterocyclic compound, 141452-01-9, name is Methyl indoline-5-carboxylate, molecular formula is C10H11NO2, 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.

(R)- l-(4-cyclopentyl- 1 ,3-dimethyl-2-oxo- 1 ,2,3,4-tetrahydropyrido [2,3-6] pyrazin-6- yl)indoline-5-carboxylic acid (i?)-6-chloro-4-cyclopentyl-l ,3-dimethyl-3,4-dihydropyrido[2,3-]pyrazin-2(lH)- one (42.0 mg, 0.15 mmol, 1 eq), methyl indoline-5-carboxylate (31.9 mg, 0.180 mmol, 1.2 eq), Pd2dba3 (6.9 mg, 0.0075 mmol, 5 mol%), XPhos (10.7 mg, 0.0225 mmol, 15 mol%) and K2C03 (82.9 mg, 0.60 mmol, 4 eq) were dissolved in tBuOH (1.5 mL, 0.1 M) and heated to 100 C for 20 hours. The mixture was filtered through celite, washed with DCM/EtOAc/MeOH and condensed. Purification by column chromatography (ISCO, 4 g silica column, 0-10%MeOH/DCM, 15 minute gradient) gave a mixture of the desired methyl ester and the (inconsequential) ethyl ester, which was used without further purification (65.56 mg). LCMS 40.48 (M+H), 435.47 (ethyl ester M+H). The resulting material was dissolved in THF (0.78 mL) and water (0.39 mL). LiOH (5.6 mg) was added and the mixture was stirred at room temperature. Due to poor solubility and sluggish conversion, an additional 5.6 mg LiOH, 0.39 mL water and 0.39 mL MeOH were added. After 2 days, the mixture was diluted with MeOH and purified by preparative HPLC to give a dark brown oil (33.84 mg, 0.08325 mmol, 53% over 2 steps. 1H NMR (400 MHz, Methanol-^) delta 8.11 (d, J= 8.6 Hz, 1H), 7.82 (dd, J= 8.6, 1.7 Hz, 1H), 7.76 (s, 1H), 7.23 – 7.16 (m, 1H), 6.24 (d, J= 8.5 Hz, 1H), 4.61 – 4.52 (m, 1H), 4.28 (q, J = 6.8 Hz, 1H), 4.06 (t, J= 8.8 Hz, 2H), 3.31 (s, 3H), 3.19 (t, J= 8.7 Hz, 2H), 2.09 (ddd, J = 17.1, 12.9, 8.7 Hz, 2H), 1.86 – 1.61 (m, 6H), 1.18 (d, J= 6.8 Hz, 3H). 13C NMR (100 MHz, cd3od) delta 169.88, 168.00, 150.16, 146.41, 132.06, 131.00, 126.64, 123.78, 121.72, 117.96, 112.26, 98.72, 58.11, 54.52, 50.70, 30.98, 30.72, 29.27, 27.49, 24.04, 23.33, 17.03. LCMS 407.48 (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 Methyl indoline-5-carboxylate, its application will become more common.

Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; BRADNER, James, E.; GRAY, Nathanael; QI, Jun; MCKEOWN, Michael, R.; BUCKLEY, Dennis; WO2015/117055; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 3484-35-3,Some common heterocyclic compound, 3484-35-3, name is 5-Methylindolin-2-one, molecular formula is C9H9NO, 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: To a solution of 3-substituted-5-benzylidene-2-thioxo-4-thiazolidinone (3a-3h, 8a-8f) (0.003 mol) in 1,4-dioxane (15 ml) was added HC(OEt)3 (2 ml) and BF3·Et2O (2 ml). The reaction mixture was heated to 80 C and stirring was continued at the same temperature for 4 h. The resulting 2-ethylthio-3-substituted-5-benzylidene-4-thiazolium fluoroborate (4a-4h, 9a-9f) was precipitated, filtered off, and dried without any additional purification, as starting material for the following reactions. To a mixture of thiazolium fluoroborate (4a-4h, 9a-9f) (0.003 mol) and indolin-2-one (11a-11f) (0.003 mol) in acetonitrile (15 ml) was added triethylamine (0.91 g, 0.009 mol) dropwise at 25 C, and the mixture was stirred for 4 h at the same temperature. The orange precipitate was collected and washed with ethyl acetate (8 ml). The crude product thus obtained was recrystallized from methanol or acetone to give compound (5a-5s, 10a-10s).

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

Reference:
Article; Wang, Shuobing; Zhao, Yanfang; Zhang, Guogang; Lv, Yingxiang; Zhang, Ning; Gong, Ping; European Journal of Medicinal Chemistry; vol. 46; 8; (2011); p. 3509 – 3518;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 6941-75-9,Some common heterocyclic compound, 6941-75-9, name is 5-Bromoisoindoline-1,3-dione, molecular formula is C8H4BrNO2, 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 fuming nitric acid (9.2 mL, 0.22 mol, 1.0 eq) pre-cooled at 0 C. was added drop wise concentrated sulfuric acid (21 mL, 0.40 mol, 1.8 eq) followed by portion-wise addition of intermediate I-55 (10 g, 44 mmol, 2.0 eq) and the resulting suspension was warmed to room temperature over 1 hour and stirred for a additional 24 hours at room temperature. The crude reaction mixture was poured onto a mixture of ice and water and the solids were collected by filtration and dried in vacuo to give intermediate I-56 (11.8 g, 98%). MS (ESI): m/z 272 (M+H+).

The synthetic route of 6941-75-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chytil, Milan; Engel, Sharon R.; Fang, Qun Kevin; Spear, Kerry L.; US2010/204214; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

15362-40-0, name is 1-(2,6-Dichlorophenyl)-2-indolinone, 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. category: indolines-derivatives

Pyrrole-2-carboxaldehyde (1 mmol) and 1-(2,6-dichlorophenyl)-2-indolinone (1 mmol) were taken in CHCl3 (solvent) and catalytic amount of piperidine (0.2 mmol) was added and then the mixture was subjected to microwave irradiations at 100 C for 1 hr. TLC was used for monitoring the progress of the reaction and after the completion of reaction, it was quenched by adding water. Later the product was extracted with CHCl3 (2 x 50 ml), dried over Na2SO4 and evaporated in vacuum. The crude product was then purified by recrystallization from CHCl3: Methanol (1:3) to get pure product 3e. Yellow Solid, yield 87.2%, mp 178-180 C; IR (KBr): 3469, 3082, 1678, 1597, 1578, 1485; 1H NMR (500 MHz, CDCl3) delta: 6.41-6.43 (m, 1H, ArH), 6.49-6.51 (m, 1H, ArH), 6.85-6.86 (m, 1H, ArH), 7.14-7.21 (m, 3H, ArH), 7.41-7.45 (m, 1H, ArH), 7.56-7.57 (s, 2H, ArH), 7.58 (s, 1H, ArH), 7.61-7.63 (m, 1H, ArH), 13.22 (s, 1H, NH); 13C NMR (125 MHz, CDCl3) delta: 109.0, 111.89, 115.25, 118.2, 121.2, 122.7, 124.9, 125.7, 126.8, 127.3, 128.9, 130.0, 130.7, 135.8, 138.7, 167.2; HRMS (ESI) m/z for C19H12Cl2N2O [M+H]+ calcd. 355.0994, found 355.0326.

The synthetic route of 15362-40-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Kaur, Jagroop; Kaur, Baljit; Singh, Palwinder; Bioorganic and Medicinal Chemistry Letters; vol. 28; 2; (2018); p. 129 – 133;,
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 32692-19-6 as follows. Formula: C8H8N2O2

General procedure: A solution of 5-nitroindoline (6) (0.5 g, 3.05 mmol) in DMF (10 mL) was treated with NaH (0.39 g, 9.75 mmol, 60% wt in mineral oil) at 0 C resulting in an orange mixture. ;The reaction mixture was then treated with 2-chloro-N,N-dimethylethanamine hydrochloride (0.87 g, 6.09 mmol) resulting in a dark red mixture. ;The reaction was heated to 90 C and stirred for 1.5 h. ;After allowing the reaction to cool to room temperature, water was added and the product was extracted into EtOAc. ;The combined ethyl acetate layer was washed with water, brine and dried (Na2SO4). ;Solvent was evaporated and the crude was purified by flash column chromatography (2 M NH3 in MeOH:CH2Cl2, 2.5:97.5) to obtain the title compound

According to the analysis of related databases, 32692-19-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Annedi, Subhash C.; Maddaford, Shawn P.; Ramnauth, Jailall; Renton, Paul; Rybak, Taras; Silverman, Sarah; Rakhit, Suman; Mladenova, Gabriela; Dove, Peter; Andrews, John S.; Zhang, Dongqin; Porreca, Frank; European Journal of Medicinal Chemistry; vol. 55; (2012); p. 94 – 107,14;; ; Article; Annedi, Subhash C.; Maddaford, Shawn P.; Ramnauth, Jailall; Renton, Paul; Rybak, Taras; Silverman, Sarah; Rakhit, Suman; Mladenova, Gabriela; Dove, Peter; Andrews, John S.; Zhang, Dongqin; Porreca, Frank; European Journal of Medicinal Chemistry; vol. 55; (2012); p. 94 – 107;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 7147-90-2, name is 5-Chloroisoindoline-1,3-dione, 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 7147-90-2, COA of Formula: C8H4ClNO2

To a solution of 5-chloro-isoindole-l,3-dione (3.63 g, 20 mmol) in DCM (150 mL) was added methylmagnesium chloride (3 M in THF, 20 mL) dropwise at 0 C. After the addition, the mixture was stirred at 0 C for 3 hours before it was quenched with satd. aq. NH4CI solution. After extraction with DCM, the organic layer was washed with brine, dried over anhy. Na2S04, filtered and concentrated in vacuo to give a crude product containing a mixture of two regioisomers (3.95 g, 100%). MS: 198.1 (M+H+).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Chloroisoindoline-1,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; AEBI, Johannes; AMREIN, Kurt; CHEN, Wenming; HORNSPERGER, Benoit; KUHN, Bernd; LIU, Yongfu; MAERKI, Hans P.; MAYWEG, Alexander V.; MOHR, Peter; TAN, Xuefei; WANG, Zhanguo; ZHOU, Mingwei; WO2013/79452; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 59-48-3, 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 59-48-3 as follows.

PREPARATION 8 5-Acetyl-2-oxindole To 95 ml. of carbon disulfide was added 27 g. (0.202 mole) of aluminum chloride, followed by the dropwise addition of a solution of 3 ml. (0.042 mole) of acetyl chloride in 5 ml. of carbon disulfide, with stirring. Stirring was continued for 5 minutes and then 4.4 g. (0.033 mole) of 2-oxindole was added. The resulting mixture was heated under reflux for 4 hours and cooled. The carbon disulfide was removed by decantation and the residue was triturated under water and recovered by filtration. After drying, 3.2 g. of the title compound was obtained, m.p. 225-227 C.

According to the analysis of related databases, 59-48-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Pfizer Inc.; US4652658; (1987); A;,
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. 552330-86-6, name is 5-Bromoisoindolin-1-one, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 5-Bromoisoindolin-1-one

A mixture of 5-bromoisoindolin-1-one (2-73, 200 mg, 0.95 mmol), 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane) (2-57, 241 mg, 0.95 mmol), KOAc (186 mg, 1.9 mmol), and Pd(dppf)C12 (69 mg, 0.095 mmol) in dioxane (5 ml) was stirred for 16 h at 60 C. Upon reaction completion, the resulting mixture was washed with H20 and extracted with ethyl acetate (50 mL x 3). The combined organic phases were concentrated under reduced pressure and the resulting residue was purified via silica gel chromatography (Pet Ether/ ethyl acetate = 10/1) to obtain intermediate 2-74 (white solid, 300 mg, 88% yield). LCMS (m/z): 260 [M + Hj.

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 552330-86-6.

Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; FONDAZIONE CENTRO SAN RAFFAELE; GRAY, Nathanael S.; BUHRLAGE, Sara; ANDERSON, Kenneth; COTTINI, Francesca; TONON, Giovanni; (288 pag.)WO2016/161145; (2016); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 883-44-3,Some common heterocyclic compound, 883-44-3, name is 2-(3-Hydroxypropyl)isoindoline-1,3-dione, molecular formula is C11H11NO3, 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 4-[(4-fluorophenyl)sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid, 1,I-di-methylethyl ester (6.7 g, 19 mmol, as prepared in Example 1, Part C) in anhydrous N,N-dimethylformamide (40 ml) at ambient temperature was added N-(3-hydroxypropyl)phthalimide (4 g, 19 mmol), followed immediately by NaH (700 mg, 20 mmol, 60% dispersion in mineral oil). After 1.5 hr, HPLC showed less than 1% of the starting Electrophile. The reaction mixture was quenched with water (60 ml). The cloudy mixture was extracted with ethyl acetate (2×100 ml). The organic layers were combined, washed with brine (1×200 ml), dried over sodium sulfate, filtered, and concentrated in vacuo to give a tan, viscous oil that crystallized from methanol (3.2 g, 52%). ESMS m/z=489 [M+H]+. This material was used without further purification.

The synthetic route of 883-44-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Freskos, John N.; Fobian, Yvette M.; Barta, Thomas E.; Becker, Daniel P.; Bedell, Louis J.; Boehm, Terri L.; Carroll, Jeffery N.; DeCrescenzo, Gary A.; Hockerman, Susan L.; Kassab, Darren J.; Kolodziej, Steve A.; McDonald, Joseph; Mischke, Deborah A.; Norton, Monica B.; Rico, Joseph G.; Talley, John J.; Villamil, Clara I.; Wang, Lijuan Jane; US2004/10019; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem