Category: indolines-derivatives

Application of 1074-82-4,Some common heterocyclic compound, 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, molecular formula is C8H4KNO2, 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.

(0331) A mixture of potassium phthalimide (100.0 g, 539.9 mmol, 1.0 equiv.), potassium carbonate (11.2 g, 81.0 mmol, 0.15 equiv.) and N,N-dimethylformamide (DMF) (200 mL) is treated with chloroacetone (47.3 mL, 54.9 g, 593.9 mmol, 1.1 equiv.) at a rate to control the internal temperature at not more than 40 C. After the addition is complete, the reaction mixture is stirred for about 12 hours at about 20-25 C. Water (333 mL) is charged to the reaction mixture at a rate to control the internal temperature at not more than 30 C. The mixture is stirred at about 20-25 C. for about 1 hour, and then the mixture is filtered. The filter cake is washed with water (200 mL), and the product is dried at about 70-80 C. under vacuum with a nitrogen flow for about 12 hours. The product phthalimidoacetone (VII-j) is obtained as a white solid (90.2 g, 97.3 wt. % purity, 80% yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Potassium 1,3-dioxoisoindolin-2-ide, its application will become more common.

Reference:
Patent; Boehringer Ingelheim International GmbH; DANG, Mai Thi Quynh; HAMPEL, Thomas Armin; KOCH, Sandra; NORDSTROM, Fredrik Lars; REEVES, Jonathan Timothy; REICHEL, Carsten; SCHOERER, Marvin; STANGE, Christian; VOLCHKOV, Ivan N.; Zhong, Li; ZIMMERMANN, Uwe Johannes; (38 pag.)US2018/251427; (2018); A1;,
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Application of 105310-75-6, A common heterocyclic compound, 105310-75-6, name is cis-2-((1,3-Dioxoisoindolin-2-yl)methyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide, molecular formula is C23H24N2O3, 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.

40% methyl amine solution (prepared by mixing methyl amine (210 g) with water (190 ml)) was added to (Z)-l -phenyl- l-diethylaminocarbonyl-2- phthalimidomethylcyclo propane compound of formula-6 (100 g) obtained from example-3 in toluene (450 ml) at 20-30C and stirred for 24 hours. After completion of the reaction both the organic and aqueous layers were separated; the aqueous layer was extracted with toluene. Both the organic layers were combined and washed with water. Carbon (8 g) was added to the organic layer, heated to 50-55C and stirred for 45 minutes. Filtered the reaction mixture and washed with toluene. Distilled off the solvent from filtrate under reduced pressure to get the title compound.Yield: 65 grams

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; MSN LABORATORIES LIMITED; THIRUMALAI RAJAN, Srinivasan; ESWARAIAH, Sajja; SATYANARAYANA, Revu; WO2012/46247; (2012); A2;,
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Electric Literature of 141452-01-9, A common heterocyclic compound, 141452-01-9, name is Methyl indoline-5-carboxylate, molecular formula is C10H11NO2, 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.

General procedure: To a 100-mL, one-necked, round-bottomed flask,sequentially charged with compound A (2.25 mmol, 1 equiv.), CS2 (11.25 mmol, 5 equiv.), K3PO4 (2.25 mmol, 1 equiv.) and 30 mL ofacetone. The mixture was stirred for 0.5 h at r.t. and then 4-(bromomethyl)benzoic acid (2.25 mmol, 1 equiv.) was added. TLCanalysis was used to indicate the completed reaction. The reactionmixture was concentrated to provide crude compound B.

The synthetic route of 141452-01-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Xie, Rui; Li, Yan; Tang, Pingwah; Yuan, Qipeng; European Journal of Medicinal Chemistry; vol. 143; (2018); p. 320 – 333;,
Indoline – Wikipedia,
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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. 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, A new synthetic method of this compound is introduced below., Computed Properties of C13H16BrNO2

5-Bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 mL) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 8O0C for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45g, 46%). 1H NMR (MeOH-d4) 7.15 (1 H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H, m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H, s). MS: [M+H]+ 318.

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; ASTEX THERAPEUTICS LIMITED; WO2008/44029; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 118289-55-7, 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.

EXAMPLE 1; 5- (2- (4- (1, 2-benzisotliiazol-3-yl)-l-piperazitiyl) ethyl)-6-chloro-1, 3-diliydro-2H-indole-2-one (Ziprasidone); In a 10 liter three-necked round bottom flask sodium carbonate (742 g) and pure water (3.06 liter) is charged. To the above stirred solution 1, 2-benzisothiazole-3-piperazinyl HCl (611 g, 2 moles) is added at ambient temperature and stirred the reaction mixture additionally for 1 hour. To the obtained suspension 2-Chloroethyl-6-chloro oxindole (430 g, 2 moles) and sodium iodide (20 g) is added. The combined reaction mixture is heated at 60 to 90 C for 20 to 30 hours. After completion of the reaction, reaction mass is cooled to ambient temperature and the slurry thus obtained is stirred for 1 hour more and then filtered. The wet tan colored crude free base is suspended in water (7.50 liter), heated to 75 to 80 C under stirring for 1 hour and filtered at 45 to 50 C temperature. Wet compound is dried at 65 to 70 C for 10 to 12 hours to get desired product in 752 gm yield (HPLC Purity 95 to 96%).

The synthetic route of 6-Chloro-5-(2-chloroethyl)indolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; WOCKHARDT LIMITED; JAWEED MUKARRAM, Siddiqui, Mohammed; MERWADE, Aravind, Yekanathsa; SINGH, Kumar, Kamlesh, Laxmi; SOLANKI, Pawan, Vrajlal; WO2005/54235; (2005); A1;,
Indoline – Wikipedia,
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These common heterocyclic compound, 172078-33-0, name is Indolin-5-ol, 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. COA of Formula: C8H9NO

Example 48 1-(6,7-Dimethoxy-quinazolin-4-yl)-2,3-dihydro-1H-indol-5-ol methanesulfonate salt Utilizing a procedure analogous to that described in Example 1 (with conversion to the methanesulfonate salt analogous to that described in Example 44), this product was prepared in 90% yield from 5-hydroxy-indoline (1.1 eq.), and 4-chloro-6,7-dimethoxy-quinazoline (1.0 eq) in i-PrOH. (M.P. 245-250 C. (dec); LC-MS: 324 (MH+); anal. RP18-HPLC RT: 2.76 min.).

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

Reference:
Patent; Pfizer Inc.; US5736534; (1998); A;,
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Some common heterocyclic compound, 61-70-1, name is 1-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. name: 1-Methylindolin-2-one

General procedure: Appropriate indolin-2-one or indoline-2-thione (0.3 g) was mixed with acetic anhydride (3 mL) and 4-dimethylaminopyridine (DMAP, 1 mol %). The mixture was heated at 150 C in a round-bottomed flask equipped with an air condenser and CaCl2 guard tube. The reaction time for each reactant is provided in [Table 2] and [Table 3]. After the completion of the reaction excess acetic anhydride was evaporated under reduced pressure. The solid residue obtained in the case of the triacetylated products was suspended in cold methanol and vacuum filtered. The product collected was thoroughly washed with hexane and dried. In the case of mono and diacetylated products the solid residue was purified using flash column chromatography (FCC) (silica gel, hexanes/ethyl acetate).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 61-70-1, its application will become more common.

Reference:
Article; Jha, Mukund; Chou, Ting-Yi; Blunt, Brian; Tetrahedron; vol. 67; 5; (2011); p. 982 – 989;,
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 337536-15-9 as follows. SDS of cas: 337536-15-9

EXAMPLE 854-(6-Amino-5-((R)-1-(5-fluoro-2-(2H-1 ,2,3-triazol-2-yl)phenyl)ethoxy)pyridin-3- yl)isoindolin-1-oneA mixture of preparation 45 (100 mg, 0.264 mmol), 4,4,5,5,4′,4,,5′,5,-Octamethyl- [2,2′]bi[[1 ,3,2]dioxaborolanyl] (1 14 mg, 1.7 eq), and potassium acetate (90.7 mg, 3.5 eq) in DMSO (1.0 mL) was deoxygenated with N2 bubbler for 30 minutes before addition of the Pd(dppf)CI2 (9.5 mg, 0.05 eq). The mixture was then heated in 80C oil bath for 3 hr. LCMS indicated disappearance of starting bromide. To the crude boronate mixture was added 4-bromoisoindolin-1-one (84 mg, 1.5 eq), CsF (120 mg, 3.5 eq) and MeOH (2 ml_). The mixture was thoroughly degassed and Pd(dppf)Cl2 (9.5 mg, 0.05 eq) was added. The mixture was heated in the microwave at 120 C for 1 hr. LCMS showed the desired product mass. Mixture was filtered and purified with a reverse phasepreparative HPLC under acidic condition to give the title compound as an amorphous white solid (57.8 mg, 50.9%).1H NMR (600 MHz, DMSO-d6) delta ppm 1.59 (d, J=6.14 Hz, 3 H), 4.07 – 4.21 (m, 1 H), 4.23 – 4.34 (m, 1 H), 5.56 (q, J=6.06 Hz, 1 H), 6.19 (s, 2 H), 6.77 (s, 1 H), 7.34 (td, J=8.26, 2.94 Hz, 1 H), 7.41 (d, J=7.42 Hz, 1 H), 7.51 (t, J=7.55 Hz, 1 H), 7.57 (s, 1 H), 7.63 – 7.67 (m, 1 H), 7.70 – 7.72 (m, 1 H), 7.72 (d, J=1.28 Hz, 2 H), 8.20 (s, 1 H), 8.64 (s, 1 H).

According to the analysis of related databases, 337536-15-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PFIZER INC.; BUNNAGE, Mark, Edward; COOK, Andrew, Simon; CUI, Jingrong, Jean; DACK, Kevin, Neil; DEAL, Judith, Gail; GU, Danlin; HE, Mingying; JOHNSON, Patrick, Stephen; JOHNSON, Ted, William; LE, Phuong, Thi, Quy; PALMER, Cynthia, Louise; SHEN, Hong; WO2011/138751; (2011); A2;,
Indoline – Wikipedia,
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Application of 84807-26-1, 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 84807-26-1 as follows.

General procedure: To a solution of 6-nitroindoline (13) (590 mg, 3.6 mmol), tert-butyl 4-oxopiperidine-1-carboxylate (860 mg, 4.3 mmol) in acetic acid (10.0 mL) was added sodium triacetoxyborohydride (1.14 g, 5.4 mmol) at 0C and the reaction mixture was stirred for 1 hr at this temperature and then heated to room temperature overnight. After the reaction completed, water was added to the the mixture and the mixture was extracted with CH2Cl2. The organic phase was washed with water and saturated NaHCO3, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to afford the crude product, which was purified by column chromatography to give the tert-butyl 4-(6-nitroindolin-1-yl) piperidine-1-carboxylate (14) 0.92 g, yield: 73.6%.

According to the analysis of related databases, 84807-26-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Tian, Jinlong; Sun, Nannan; Yu, Mingcheng; Gu, Xianfeng; Xie, Qiong; Shao, Liming; Liu, Jin; Liu, Li; Wang, Yonghui; European Journal of Medicinal Chemistry; vol. 167; (2019); p. 37 – 48;,
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 20870-79-5 as follows. Application In Synthesis of 5-Nitroindolin-2-one

Example 67 5-Nitro-indoline (2) A suspension of compound 1 (5 g, 28.1 mmol) in THF (10 mL) was treated with a BH3-THF complex (84 mL, 84 mmol, 1.0 M in THF) and the resulting brown red suspension was refluxed overnight. The reaction was cooled in an ice-bath and methanol (125 mL) was added resulting in orange/red solution which was stirred for half an hour and then concentrated. Methanol (200 mL) was added again and the solution was refluxed for 2 hrs and then concentrated. The residue was subjected to a large silica gel filter with methanol as eluent resulting in a brown solid (2.5 g, 54% yield). 1H-NMR (DMSO-d6) delta 7.90 (dd, J=8.7, 2.4 Hz, 1H), 7.83 (s, 1H), 7.26 (s, 1H), 6.44 (d, J=8.7 Hz, 1H), 3.66 (t, J=9.0 Hz, 2H), 3.04 (t, J=9.0 Hz, 2H).

According to the analysis of related databases, 20870-79-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MADDAFORD, Shawn; RAMNAUTH, Jailall; RAKHIT, Suman; PATMAN, Joanne; ANNEDI, Subhash C.; ANDREWS, John; DOVE, Peter; SILVERMAN, Sarah; Renton, Paul; US2008/234237; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem