Month: March 2021

Application of 132898-96-5, A common heterocyclic compound, 132898-96-5, name is 2,3-Dioxoindoline-5-sulfonyl chloride, molecular formula is C8H4ClNO4S, 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 stirred solution of the N-Boc-protected pyrrolidine (1.0 mmol) in dry DCM (3 mL) at 0 C under argon atmosphere, TFA (1.14 g, 10.0 mmol) was added dropwise. The obtained solution was stirred at 0 C for 30 min followed by stirring at r.t. for 2 h. Subsequently, the solution was poured to cold 10% aq. NaOH (15 mL) and extracted with DCM (3 ¡Á 15 mL). The combined organic phases were dried over MgSO4 and concentrated under reduced pressure resulting in the corresponding unprotected pyrrolidine, which was used in the next step without further purification. The free pyrrolidine (ca. 1 mmol) from the previous step was then taken up in CHCl3 (2.2 mL) and DIPEA (2.0 mmol) was added. The solution was added dropwise to a stirred solution of 5-chlorosulfonyl isatin (1.5 mmol) in CHCl3/THF (1:1, 15 mL) at room temperature. The resulting mixture was stirred further for 1 h and the solvent was removed under reduced pressure. After purification by flash column chromatography the target isatin sulfonamide was obtained.

The synthetic route of 132898-96-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Limpachayaporn, Panupun; Riemann, Burkhard; Kopka, Klaus; Schober, Otmar; Schaefers, Michael; Haufe, Guenter; European Journal of Medicinal Chemistry; vol. 64; (2013); p. 562 – 578;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 132898-96-5, name is 2,3-Dioxoindoline-5-sulfonyl chloride, molecular formula is C8H4ClNO4S, 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. Recommanded Product: 132898-96-5

General procedure: A mixture of cis-N-benzyl-2,5-bis(methoxymethyl)pyrrolidine (18a) (620 mg, 2.49 mmol, 1.00 equiv.) and 10% Pd/C (62 mg, 10% w/w) in MeOH (12 mL) was stirred in an autoclave at ambient temperature under H2 atmosphere (20 atm) for 6 h. After this time, the mixture was filtered through Celite and washed again with MeOH. The solvent was removed under reduced pressure to obtain the corresponding unprotected bis(methoxymethyl)pyrrolidine as a light yellow oil. The solution of obtained free amine cis-2,5-bis(methoxymethyl)pyrrolidine and DIPEA (766 muL, 4.40 mmol, 2.00 equiv.) in CHCl3 (5 mL) was added dropwise to a stirred solution of 5-chlorosulfonyl isatin (1.08 g, 4.40 mmol, 2.00 equiv.) in CHCl3/THF (1:1, 50 mL) at room temperature. The resulting mixture was stirred further for 2 h and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 90% EtOAc in cyclohexane) to yield a yellow solid (723 mg, 1.96 mmol, 89%). M.p. 168 C. 1H NMR (400 MHz, DMSO-d6): delta = 11.46 (br s, 1H, 1-NH), 8.05 (dd, 3JH,H = 8.3 Hz, 4JH,H = 2.0 Hz, 1H, 6-CH), 7.80 (d, 4JH,H = 1.9 Hz, 1H, 4-CH), 7.09 (d, 3JH,H = 8.3 Hz, 1H, 7-CH), 3.73-3.58 (m, 2H, 12-CH, 15-CH), 3.52-3.20 (m, 4H, 16-CH2, 19-CH2), 3.37 (s, 6H, 18-CH3, 21-CH3), 1.78-1.62 (m, 2H, 13-CHa, 14-CHa), 1.57-1.37 (m, 2H, 13-CHb, 14-CHb) ppm. 13C NMR (100 MHz, DMSO-d6): delta = 182.9 (3-CO), 159.4 (2-CO), 153.6 (8-CN), 136.7 (6-CH), 130.8 (5-CSO2), 123.1 (4-CH), 118.1 (9-CCO), 112.7 (7-CH), 74.4 (2C, 16-CH2, 19-CH2), 59.9 (2C, 12-CH, 15-CH), 58.4 (2C, 18-CH3, 21-CH3), 26.9 (2C, 13-CH2, 14-CH2) ppm. HRMS (ESI+, MeOH): m/z = 391.0931 [M + Na]+, 423.1194 [M + Na + MeOH]+; calcd. 391.0934 for C16H20N2O6S + Na, 423.1196 for C16H20N2O6S + Na + MeOH.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 132898-96-5, its application will become more common.

Reference:
Article; Limpachayaporn, Panupun; Riemann, Burkhard; Kopka, Klaus; Schober, Otmar; Schaefers, Michael; Haufe, Guenter; European Journal of Medicinal Chemistry; vol. 64; (2013); p. 562 – 578;,
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. 39603-24-2, name is 5,7-Dimethylindoline-2,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Formula: C10H9NO2

General procedure: A mixture of phenylhydrazine (1 mmol), 3-aminocrotononitrile (1 mmol), and InCl3 (0.1 mmol) in water (10 ml) was added to isatin (1 mmol) and the reaction mixture heated under reflux at 100 C for 10 min. After completion of the reaction (TLC), the reaction mixture was cooled to room temperature; the precipitate was filtered off and washed with methanol to obtain pure 13 as a colorless solid. Spectroscopic data for all the compounds are given below.

According to the analysis of related databases, 39603-24-2, the application of this compound in the production field has become more and more popular.

Reference:
Article; Balamurugan, Kamaraj; Perumal, Subbu; Menendez, J. Carlos; Tetrahedron; vol. 67; 18; (2011); p. 3201 – 3208;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 19727-83-4, name is 6-Nitroindoline, molecular formula is C8H8N2O2, 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. Recommanded Product: 19727-83-4

5-Trifluoromethyl-7-pyridono[5,6-e]indoline (Compound 419, structure 49A of Scheme XLV, where R1 =trifluoromethyl, R2 =H) 6-Aminoindoline A solution of 6-nitroindoline (1 g, 6.1 mmol) in 50 mL of ethyl acetate was hydrogenated under an atmosphere of hydrogen with Pd-C 10% (100 mg) at rt for 3 h. Filtration over celite afforded 1.0 g (98%) of 6-aminoindoline. Data for 6-aminoindoline: 1 H NMR (400 MHz, CDCl3) 7.40 (d, J=7.4, 1H), 6.05 (d, J=2.0, 1H), 6.03 (d, J=7.5, 1H), 3.67 (bs, 1H), 3.49 (t, J=8.1, 2H), 3.48 (bs, 2H), 2.90 (t, J=8.2, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19727-83-4, its application will become more common.

Reference:
Patent; Ligand Pharmaceuticals Incorporated; US5688810; (1997); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

340702-10-5, name is 6-Fluoroisoindolin-1-one, 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. Recommanded Product: 340702-10-5

To a 0 C suspension of 6-fluoroisoindoline-l-one (8.0 g, 5.3 mmol) in concentrated H2S04 was added drop-wise a pre-cooled mixture of concentrated H2S04 (26 mL) and nitric acid (6 mL) while keeping the reaction mixture below 5 C. After addition, the reaction mixture was slowly warmed to room temperature during overnight. Ice (50 g) was added to the mixture and the solid was collected and dried, then washed with MTBE (50 mL) and ethyl acetate (50 mL) to give the desired product as a light yellow solid ( 5.1 g, 50%). MS: (ES) m/z calculated for C8H6FN203[M+H]+ 197.2, found 197.2.

The synthetic route of 340702-10-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CHEMOCENTRYX, INC.; CHEN, Xi; DRAGOLI, Dean, R.; FAN, Junfa; KALISIAK, Jaroslaw; KRASINSKI, Antoni; LELETI, Manmohan, Reddy; MALI, Venkat; MCMAHON, Jeffrey; SINGH, Rajinder; TANAKA, Hiroko; YANG, Ju; YU, Chao; ZHANG, Penglie; (198 pag.)WO2017/87607; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 6341-92-0, name is 6-Chloroisatin, 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 6341-92-0, Recommanded Product: 6-Chloroisatin

Step 3: 6′-Chlorospiro[1,3-dioxane-2,3′-indol]-2′(1’H)-one A mixture of 6-chloroisatin (10.39 g, 57.2 mmol), 1,3-propanediol (10.74 mL, 143 mmol, 2.5 eq) and p-toluenesulfonic acid monohydrate (2.18 g, 11.4 mmol, 0.2 mol %) in benzene (IL) was heated to reflux under a Dean Stark Trap for 20 hr. Additional p-toluenesulfonic acid (5.44 g, 0.5 mol %) and 1,3-propanediol (5 mL) was added and the reaction was refluxed for an additional 4 hr then stirred at room temperature overnight. The reaction was concentrated and the residue was taken up in EtOAc, washed with sat. aq. NaHCO3 (3*), water (3*), dried over Na2SO4, filtered, and concentrated. The crude product was purified on Biotage KP silica gel eluding with 96/4 (CH2Cl2/CH3OH) to give an orange gummy solid (13.25 g, 97%) which was triturated with CH3OH (100 mL) to give the title compound as an orange colored solid (8.85 g, 64.6% yield). NMR (400 MHz, DMSO-d6): consistent. MS: (API-ES-) m/z 237/239 [M-H]1 chlorine pattern observed.

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

Reference:
Patent; Wyeth; US2005/250798; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

3485-84-5, name is N-Vinylphthalimide, 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. Quality Control of N-Vinylphthalimide

Preparation 9 2-{2-[4-(2-Hydroxy-ethyl)-phenyl]-vinyl}-isoindole-1,3-dione To a solution of 2-(4-bromophenyl)ethanol (48.3 g) in acetonitrile (480 mL) was added diisopropylethylamine (46.6 g), N-vinylphthalimide (43.7 g) and tri-o-tolylphosphine (7.31 g) and the mixture was purged with nitrogen gas three times. Palladium acetate (2.7 g) was added and the mixture was stirred at 90 C. for 21 hr under nitrogen. The reaction was cooled and the precipitated product collected by filtration. The resulting solid was re-dissolved in dichloromethane and ethyl acetate and filtered through silica gel. The filtrate was concentrated in vacuo to give the title compound, 24 g. 1H NMR (400 MHz, CDCl3) delta=2.81-2.84 (t, 2H), 3.82-3.90 (t, 2H), 7.23-7.26 (d, 2H), 7.32-7.26 (d, 1H), 7.40-7.43 (d, 2H), 7.61-7.64 (d, 1H), 7.66-7.78 (d, 2H), 7.86-7.88 (d, 2H) ppm.

The synthetic route of 3485-84-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Jones, Lyn Howard; Roberts, Dannielle Frances; Strang, Ross Sinclair; US2010/10040; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 20780-72-7, 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. 20780-72-7, name is 4-Bromoisatin, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: In a general procedure, a mixture of 4-chloroindoline-2,3-dione(4.4 mmol), K2CO3 (1.8 g), P-chlorobenzyl bromide (1.1 g) in DMF(10 mL) was stirred at room temperature for 4 h under argon. Thenthe reaction was quenched by adding excess ice-water and stirredfor 30 min. The suspensionwas filtered and the residuewas dried toafford 4-chloro-1-(4-chlorobenzyl)indoline-2,3-dione (1.34 g, 90percent)as a red solid without further purification. This was directly used in the next step; NH2OHHCl (1.5 mmol) was added to a solution of 4-chloro-1-(4-chlorobenzyl)indoline-2,3-dione (1.4 mmol) in Pyridine(5 mL) and the resulting mixture was heated to 110 C andstirred for 2 h. After cooling to room temperature, the resultingsolution was poured into aqueous HCl (1 M, 50 mL) and extractedwith EtOAc (350 mL). The combined organic layer was washedwith brine (330 mL), dried over Na2SO4, concentrated underreduced pressure and then recrystallized to produce 5a (382 mg,85percent) as a yellow solid. The derivatives 5b, 5c were preparedthrough this procedure by using 4-bromoindoline-2,3-dione and 4-iodoindoline-2,3-dione as material.

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

Reference:
Article; Li, Yuyin; Pan, Guojun; Chen, Yue; Yang, Qian; Hao, Tiantian; Zhao, Lianbo; Zhao, Long; Cong, Yusheng; Diao, Aipo; Yu, Peng; European Journal of Medicinal Chemistry; vol. 145; (2018); p. 370 – 378;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 264916-06-5, 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. 264916-06-5, name is tert-Butyl 5-aminoisoindoline-2-carboxylate belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Step-1: tert-butyl 5-((2-ethyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)isoindoline-2-carboxylate To a stirred solution of 2-ethyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (0.2 g 0.5790 mmol, 1.0 eq) in (5.0 mL) of toluene was added m-CPBA (0.280 g, 1.158 mmol, 2 eq) and allowed to stir at rt for 30 min. followed by addition of tert-butyl 5-aminoisoindoline-2-carboxylate (0.176 g, 0.7527 mmol, 1.3 eq) and DIPEA (0.3 ml 1.737 mmol, 3.0 eq) and allowed to stir at rt for overnight. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2*20 mL). The combined organic layers were washed with water (30 mL), brine (30 mL), dried over Na2SO4, concentrated and purified by combi flash [silica gel-100-200 mesh; elution 0-35% EtOAc in Hexane] to afford the desired compound, tert-butyl 5-((2-ethyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)isoindoline-2-carboxylate (0.100 g, 49.52%) as white 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, tert-Butyl 5-aminoisoindoline-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; giraFpharma LLC; Chakravarty, Sarvajit; PHAM, Son Minh; Kankanala, Jayakanth; AGARWAL, Anil Kumar; PUJALA, Brahmam; SONI, Sanjeev; ARYA, Satish K.; PALVE, Deepak; Gupta, Ashu; KUMAR, Varun; (498 pag.)US2019/106427; (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. 16800-68-3, name is 1-Acetylindolin-3-one, This compound has unique chemical properties. The synthetic route is as follows., Formula: C10H9NO2

General procedure: 1a (35.0 mg, 0.2 mmol, 1 equiv.), tert-BuOK (22.4 mg, 0.2 mmol, 1.0 equiv.) were added to a Schlenk tube. Then 2 ml THF was added using a syringe. The reaction mixture was stirred 15min,and then added iodonium salt 2 (0.2 mmol, 1.0 eq). The reaction was stirred at 30C for 10 hours.After cooling to room temperature, the solvent was removed in vacuo and the residue was purifiedby silica gel using a proper eluent (EtOAc/Hexane) to afford the desired products

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 16800-68-3.

Reference:
Article; Zhang, Yanxia; Han, Jianwei; Liu, Zhen-Jiang; Synlett; vol. 26; 18; (2015); p. 2593 – 2597;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem