Month: February 2021

Application of 3891-07-4,Some common heterocyclic compound, 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, molecular formula is C10H9NO3, 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.

This compound was obtained by mixing fuming nitric acid (1.0 mmol) and the precursor compound (0.10 mmol) at – 5 C and stirring for 2 h (Scheme 1). The reaction mixture was poured into a mixture of water and ice. The pH was adjusted to 6 by adding CaCO3. The obtained white solid was vacuum filtered, with yield 93%; Mp 87.1-89.5 C. IR (ATR): 3062, 3030, 2978, 2886, 1774, 1716, 1608, 1422, 1402, 1288, 982, 870, 722, 530. 1H NMR (200 MHz, DMSO-d6): 3.95 (t, 2H), 4.71 (t, 2H), 7.86 (br s,4H). 13C NMR (50 MHz, DMSO-d6): 34.8, 70.8, 123.1, 131.4, 134.4, 167.5. Anal. Calcd. for C10H8N2O5. Calcd. (%): C, 50.85; H, 3.41; N, 11.86. Found (%): C, 51.09; H, 3.32; N, 11.77.

The synthetic route of 3891-07-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Godin, Adriana M.; Araujo, Debora P.; Menezes, Raquel R.; Brito, Ana Mercy S.; Melo, Ivo S.F.; Coura, Giovanna M.E.; Soares, Darly G.; Bastos, Leandro F.S.; Amaral, Flavio A.; Ribeiro, Lucas S.; Boff, Daiane; Santos, Julliana R.A.; Santos, Daniel A.; Teixeira, Mauro M.; De Fatima, Angelo; Machado, Renes R.; Coelho, Marcio M.; Pharmacology, Biochemistry and Behavior; vol. 122; (2014); p. 291 – 298;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 667463-64-1, name is 6-Bromo-1-methylindoline-2,3-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 667463-64-1, Recommanded Product: 6-Bromo-1-methylindoline-2,3-dione

Step 2: Synthesis of Intermediate 1-12.2 1-12.1 (15.0 g, 63 mmol) and hydrazine hydrate (30 mL, 618 mmol) are heated to 125 C for 72 h. To the cool reaction mixture DCM is added and extracted with water and 1 M HC1. The organic layer is dried over MgSC>4 and concentrated. The crystallized residue is dissolved in DCM, methanol is added and the DCM is removed in vacuo. The crystallized product is filtered by sunction and washed with cold methanol. Yield 63%, m/z 226/228 [M+H]+, rt 1.16 min, LC-MS Method V001 003.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromo-1-methylindoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRAUERT, Matthias; GRUNDL, Marc; HAEBEL, Peter, Wilhelm; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; BINDER, Florian; VINTONYAK, Viktor; WO2014/140075; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 14192-26-8, These common heterocyclic compound, 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, 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.

A stirred solution of methyl 2-oxoindoline-6-carboxylate (D1) (2.0 g, 10.47 mmol) in acetic anhydride (16 ml) was heated to 130 C under inert atmosphere for 6 h. After complete consumption of the starting material (monitored by TLC), the reaction mixture was cooled to approximately 21 C. The precipitate was filtered, washed with n-hexane (2 x 50 ml) and dried in vacuo to afford compound D2 as a yellow solid (1.5 g, 61.5%).1H NMR (400 MHz, DMSO -de)6 8.66 (s, 1 H), 7.82 (d, J = 8.0 Hz, 1 H), 7.48 (d, J = 8.0 Hz, 1 H), 3.91 (s, 2H), 3.87 (s, 3H), 2.57 (s, 3H)

The synthetic route of 14192-26-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SYNTHIS, LLC; THOMAS-KARYAT, Dori A.; (0 pag.)WO2020/13803; (2020); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 16078-34-5,Some common heterocyclic compound, 16078-34-5, name is 1-(2,3-Dihydro-1H-indol-5-yl)-ethanone, molecular formula is C10H11NO, 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 I:Methanesulfonyl chloride was added dropwise to a stirred solution of 1-(indolin-5-yl)ethanone and 5 mL of pyridine under N2. The reaction was stirred at room temperature overnight. When complete as determined by HPLC using the protocol described in Example 2 above, as well as by TLC (8/2 PE/EtOAc), the solvent was evaporated, the evaporation residue was dissolved in 50 mL ethyl acetate, washed with 100 mL cold 0.5M HCl and then with brine and finally dried on Na2SO4. The solvent was evaporated and the product was used in the next step without further purification (400 mg, yield 38%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-(2,3-Dihydro-1H-indol-5-yl)-ethanone, its application will become more common.

Reference:
Patent; Dynamix Pharmaceuticals LTD.; US2012/302609; (2012); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 32692-19-6, A common heterocyclic compound, 32692-19-6, name is 5-Nitroindoline, molecular formula is C8H8N2O2, 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.

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 (0.4 g, 56%) as a solid. 1H NMR (DMSO-d6) delta 7.96 (dd, 1H, J = 2.1, 8.7 Hz), 7.79 (d, 1H, J = 2.1 Hz), 6.49 (d, 1H, J = 9.0 Hz), 3.72 (t, 2H, J = 8.7 Hz), 3.39 (t, 2H, J = 6.6 Hz), 3.04 (t, 2H, J = 8.7 Hz), 2.44 (t, 2H, J = 6.3 Hz), 2.18 (s, 6H).

The synthetic route of 32692-19-6 has been constantly updated, and we look forward to future research findings.

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

Synthetic Route of 1254319-51-1,Some common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, 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.

Potassium acetate (294 mg, 3.00 mmol), bis(pinacolato)diboron (305 mg, 1.200 mmol), 6-bromo-2- methylisoindolin-l-one (271 mg, 1.200 mmol) and 2nd Generation XPHOS precatalyst (59.0 mg, 0.075 mmol) were added to a 8 mL reaction vial equipped with a stir bar. The vial was evacuated and charged 3x with nitrogen. 1,4-Dioxane (8 mL) was added, the vial was again evacuated and charged (3x) with nitrogen, and the borylation reaction was heated to 100C. Monitored by LCMS; once borylation was complete the reaction was cooled to room temperature and 2-chloro-3 -(-(( 1- fluorocyclopentyl)methyl)-lH-pyrazol-4-yl)-6-methylpyridine (INTERMEDIATE F7; 294 mg, 1.0 mmol) and l, -bis(di-tert-butylphosphino)ferrocene palladium dichloride (48.9 mg, 0.075 mmol) were added to the reaction. The vial was evacuated and charged 3x with nitrogen, then added 3M aqueous K2C03 (1.0 mL, 3.00 mmol). The reaction was then heated to 70C overnight. LCMS shows reaction is substantially complete. Cooled to room temperature, then partitioned between water and ethyl acetate. The organic was filtered over a bed of sodium sulfate. The aqueous was extracted twice more with ethyl acetate, and the organic from those extractions was used to wash the sodium sulfate as well. The combined filtrate was evaporated and taken up again in DCM, then purified by silica gel chromatography, eluting with 20-100% 3 : 1 EtOAc:EtOH in hexanes. The major peak was isolated and the volatiles were evaporated. The solid was scraped to a small particle size and treated with diethyl ether. The suspension was filtered and the solid was collected as the title compound. MS: 405 (M+l). 1H NMR (500 MHz, CDC13): delta 7.89 (s, 1H), 7.67 (d, J=7.5 Hz, 1H), 7.58 (d, J=7.7 Hz, 1H), 7.39 (d, J=7.7 Hz, 1H), 7.21 (s, 1H), 7.18 (d, J=7.8 Hz, 1H), 7.04(s, 1H), 4.39 (s, 2H), 4.23 (d, J=21.6 Hz, 2H), 3.20 (s, 3H), 2.62 (s, 3H), 1-77-1.58 (m, 8H).

The synthetic route of 1254319-51-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MSD R&D (CHINA) CO., LTD.; ACTON, John, J., III; BAO, Jianming; DENG, Qiaolin; EGBERTSON, Melissa; FERGUSON, Ronald, III; GAO, Xiaolei; HARRISON, Scott Timothy; KNOWLES, Sandra, L.; LI, Chunsing; LO, Michael Man-Chu; MAZZOLA, Robert, D., Jr.; MENG, Zhaoyang; NA, Meng; RUDD, Michael, T.; SELYUTIN, Oleg, B.; TELLERS, David, M.; TONG, Ling; ZHANG, Fengqi; (195 pag.)WO2019/5587; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 18711-13-2,Some common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, molecular formula is C8H3Cl2NO2, 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: TiCl4 (0.7 mL, 6 mmol)was added to a stirred suspension of Zn powder (0.78 g, 12 mmol) in freshlydistilled anhydrous THF (15 mL) at room temperature (rt) under a dry N2atmosphere. After completion of the addition, the mixture was refluxed for 2 h.The suspension of the low-valent titanium reagent thus-formed was cooled tort. A solution of isatin or its derivatives 1 or 3 (2 mmol) in THF (10 mL) wasadded dropwise. The mixture was stirred at room temperature for about 5 minunder N2. After this period, the thin layer chromatography (TLC) analysis of themixture showed the reaction completed. The reaction mixture was quenchedwith 3% HCl (15 mL) and extracted with CHCl3 (3 50 mL). The combinedextracts were washed with water (3 50 mL) and dried over anhydrousNa2SO4. After evaporation of the solvent under reduced pressure, the crudeproduct was purified by column chromatography (petroleum ether/ethylacetate = 5:1) to give the pure products 2 or 4.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4,7-Dichloroindoline-2,3-dione, its application will become more common.

Reference:
Article; Lin, Wei; Hu, Ming-Hua; Feng, Xian; Fu, Lei; Cao, Cheng-Pao; Huang, Zhi-Bin; Shi, Da-Qing; Tetrahedron Letters; vol. 55; 14; (2014); p. 2238 – 2242;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 603-62-3, These common heterocyclic compound, 603-62-3, name is 3-Nitrophthalimide, 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.

In a 2500 mL round bottom flask containing 0.52 mol (100 g) of 3-nitrophthalimide, Add anhydrous ethanol 800mL, Under stirring, 385 mL of a methanolic solution of KOH at a concentration of 80 g ¡¤ L -1 (1 h addition, 0.55 mol KOH) was added dropwise and stirring continued for 3 h at room temperature, filter, The resulting white solid was rinsed with absolute ethanol, drying, The quality of 119g.

The synthetic route of 603-62-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chinese Academy Of Agricultural Sciences Plant Protection Institute; Mei Xiangdong; Si Weijie; Zhang Tao; Ning Jun; (17 pag.)CN104447498; (2017); B;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 118-29-6, 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. 118-29-6, name is 2-(Hydroxymethyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

To a mixture of compound 2,3,3-Trimethylindolenine (1) (2.0 g, 12.5 mmol, 1.1 eq.) and A (Hydroxymethyl)phthalimide (3) (2.02 g 11.4 mmol, 1 eq.) were added 14.7 mL of concentrated sulfuric acid and the system stirred at room temperature for 6 days. The reaction was then poured over ice and made basic with concentrated aqueous ammonium hydroxide. After crystallizing at -20 C overnight, the resulting precipitate was filtered, rinsed with ice cold water, and dried under vacuum to give indolenine 4 as a light yellow shiny crystalline solid. Yield 88.3%. XH NMR (400 MHz, CDCl3); d 7.82-7.87 (m, 2H, Ar- H); 7.67-7.72 (m, 2H, Ar-H); 7.44-7.48 (m, 1H, Ar-H); 7.35-7.42 (m, 2H, Ar-H); 4.87 (s, 2H,CH2); 2.25 (s, 3H, CH3) 1.28 (s, 6H, CH3).

The chemical industry reduces the impact on the environment during synthesis 2-(Hydroxymethyl)isoindoline-1,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE; SIMBERG, Dmitri; SMITH, Weston J.; (107 pag.)WO2019/126565; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 2058-74-4, These common heterocyclic compound, 2058-74-4, name is 1-Methylisatin, 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: Sulfonated-b-cyclodextrin (b-CD-SO3H) (0.1 mmol) was dissolved in water(2 mL) at room temperature by stirring to get the clear solution. Then thereaction was shifted to reflux with addition of isatin (1 mmol) and indole(2 mmol) with constant stirring. The progress of the reaction was monitored byTLC. After completion of reaction, it was cooled to room temperature andfiltered, to get the solid. The crude product was recrystallized from aqueousethanol (60:40) giving pure 3,3-di(indolyl)indolin-2-ones.

The synthetic route of 2058-74-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Tayade, Yogesh A.; Patil, Dipak R.; Wagh, Yogesh B.; Jangle, Asha D.; Dalal, Dipak S.; Tetrahedron Letters; vol. 56; 5; (2015); p. 666 – 673;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem