Category: indolines-derivatives

Synthetic Route of 169037-23-4, These common heterocyclic compound, 169037-23-4, name is 5-(Trifluoromethoxy)indoline-2,3-dione, 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: A mixture of bisarylidenepiperidin-4-one (1.36 mmoL), isatin (2.72 mmoL) and L-phenylalanine (2.72 mmoL) were heated with stirring in [bmim]Br medium (3 mL) for 1 h at 100 C. After completion of the reaction (TLC), ethyl acetate (2 x 5 mL) was added and the reaction mixture was stirred for 10 min. The organic layer was removed under reduced pressure and the crude product was purified by column chromatography (ethyl acetate:hexane v/v 3:7). 5′-Benzyl-4′-(m-nitrophenyl)-5-(trifluoromethoxy)spiro[3,2′]oxindolopyrrolidino-4′-(m-nitrophenyl)-1?-styryl-5-benzylidene-spiro[3′.3?]piperidin-4?-one (5l): Melting point 296-298 C; white solid, 94%; 1H-NMR (CDCl3, 400 MHz): delta/ppm 5.05 (d, J = 14.64 Hz, 1H), 4.75-4.77 (m, 1H), 4.30 (d, J = 10.24 Hz, 1H), 3.86 (d, J = 13.92 Hz, 1H), 3.83 (d, J = 16.92 Hz, 1H), 3.49 (d, J = 15.4 Hz, 1H), 3.10 (d, J = 11.72 Hz, 1H), 2.73-2.77 (dd, J = 13.96, 8.08 Hz, 1H), 2.74 (d, J = 13.92 Hz, 1H), 7.01-6.68 (m, 2H), 7.18-7.82 (m, 21H,Ar); 13C-NMR (CDCl3, 100 MHz): delta/ppm 40.6, 47.4, 52.1, 53.3, 62.8, 65.6, 70.9, 98.8, 110.2, 121.9, 122.4, 122.5, 112.5, 123.6, 124.4, 124.5, 126.4, 126.5, 126.7, 128.7, 128.8, 128.9, 129.2, 129.4, 129.9, 132.4, 132.9, 135.6, 136.3, 137.7, 138.7, 139.9, 144.4, 179.8, 198.7. EI-MS: m/z 801 (M+). Anal. Calcd for C44H34F3N5O7: C, 65.91; H, 4.27; N, 8.73; Found: C, 65.99; H, 4.39; N, 8.86.

Statistics shows that 5-(Trifluoromethoxy)indoline-2,3-dione is playing an increasingly important role. we look forward to future research findings about 169037-23-4.

Reference:
Article; Arumugam, Natarajan; Almansour, Abdulrahman I.; Kumar, Raju Suresh; Govindasami, Periyasami; Al-thamili, Dhaifallah M.; Krishnamoorthy, Rajapandian; Periasamy, Vaiyapuri Subbarayan; Alshatwi, Ali A.; Mahalingam; Thangamani, Shankar; Menendez, J. Carlos; Molecules; vol. 23; 5; (2018);,
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. 6326-79-0, name is 6-Bromoisatin, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 6326-79-0

Bis(2-methoxyethyl)aminosulfur trifluoride (deoxo-fluor, 44.25 mL, 22.12 mmol, 50% solution in THF) was added dropwise over 30 min to a suspension of 6-bromoisatin (2.0 g, 8.75 mmol) in DCM (90 mL) at rt with stirring. After 24 h the reaction was cautiously quenched with saturated sodium hydrogen carbonate solution (40 mL) solution at 0 C. The layers were separated and the organics extracts dried (hydrophobic frit/phase separator) and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with 20% EtOAc in iso-hexane to afford the subtitled compound as an orange solid (1.63 g, 74%). 1H NMR (400 MHz, CH3OH-d4): delta 7.50-7.46 (m, 1H), 7.36 (dd, 1H), 7.18 (d, 1H), (one exchangeable not observed).

According to the analysis of related databases, 6326-79-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; LONN, Hans Roland; CONNOLLY, Stephen; SWALLOW, Steven; KARLSSON, Staffan PO; AURELL, Carl-Johan; PONTEN, John Fritiof; DOYLE, Kevin James; VAN DE POEL, Amanda Jane; JONES, Graham Peter; WATSON, David Wyn; MACRITCHIE, Jaqueline Anne; PALMER, Nicholas John; US2015/210655; (2015); A1;,
Indoline – Wikipedia,
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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 104618-31-7 as follows. HPLC of Formula: C14H15NO3

EXAMPLE 1: 4- (Phthalimido) -cyclohexanone [0034] 4- (Phthalimido) -cyclohexanol (146 g) was mixed with AcOEt (1000 mL) , after which and NaBr (8 g) and TEMPO(0.5 g) was added. 1000 mL of NaClO (10 %) was added in portions and the reaction mixture was adjusted using NaHCtheta3 to pH 7- 8 to maintain the temperature between 5 and 20 0C. After the reaction was completed, the aqueous layer was separated and the organic layer was washed with brine (400 mL) and dried over Na2SO4. The solvent was removed under reduced pressure to give the product as white solid (95 % yield) .

According to the analysis of related databases, 104618-31-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CHIRAL QUEST, INC.; WEI, Yuan; LI, Tianqiao; CHI, Yongxiang; ZHU, Jingyang; WO2010/78250; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 104618-32-8, 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. 104618-32-8 name is 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, 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.

Example 14 3-Amino-6-n-butyloxy-1,2,3,4-tetrahydrocarbazole oxalate Reaction of 4-phthalimidocyclohexanone (1.12 g) with 4-n-butyloxyphenyl hydrazine hydrochloride (1.00 g) and subsequent deprotection by the method described in example 3, gave the title compound free base. This was treated with oxalic acid to give the oxalate salt (0.47 g), mp 227-229 C.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; Smithkline Beecham plc; US5827871; (1998); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 6941-75-9, 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 6941-75-9 as follows.

Step 1: tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate To a solution of 5-bromo-1H-isoindole-1,3(2H)-dione (4 mmol) in THF (10 mL) was added borane-dimethyl sulfide complex (2M in THF, 14 mL) at 0 C. The reaction mixture was allowed to stir at reflux overnight and was then cooled to 0 C. The reaction mixture was quenched by the slow addition of MeOH (10 mL) and then 2N HCl (10 mL). The reaction mixture was allowed to stir at reflux for 3 hr and then concentrated. Water (10 mL) was added to the residue. Remaining starting material was removed by extraction with DCM. To the aqueous solution was added 4N NaOH until pH>9. The solution was extracted with DCM. The organic solutions from this basic extraction were combined, dried over Na2SO4, filtered and concentrated to give 5-bromoisoindoline, which was dissolved in THF (20 mL). To this solution was added potassium carbonate (8 mmol) in water (1 mL), and BOC2O. The reaction mixture was allowed to stir at rt over the weekend. The reaction mixture was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (2.5 mmol, 60%).

According to the analysis of related databases, 6941-75-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Millennium Pharmaceuticals, Inc.; US2008/171754; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 132898-96-5, name is 2,3-Dioxoindoline-5-sulfonyl chloride, 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. Safety of 2,3-Dioxoindoline-5-sulfonyl chloride

Step 3: 5-({(2S)-2-[(4-methylpiperazin-1-yl)methyl]pyrrolidin-1-yl}sulfonyl)-1H-indole-2,3-dione The title compound was prepared from 2,3-dioxo-2,3-dihydro-1H-indole-5-sulfonylchloride and 1-methyl-4-[(2S)-pyrrolidin-2-ylmethyl]piperazine according to a procedure similar to that of step 1 of Example 12. NMR (400 Mz, DMSO-d6): consistent.

The synthetic route of 2,3-Dioxoindoline-5-sulfonyl chloride has been constantly updated, and we look forward to future research findings.

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

Application of 6341-92-0, The chemical industry reduces the impact on the environment during synthesis 6341-92-0, name is 6-Chloroisatin, I believe this compound will play a more active role in future production and life.

General procedure: In a 25 mL round bottom flask, isatins 1 (1 mmol), 3-phenylisoxazol-5(4H)-one 2 (1 mmol) or 3-ethylisoxazol-5(4H)-one 7 (1 mmol), pyrazol-5-amine 3 (1 mmol) or 6-aminopyrimidine-2,4-(1H,3H)-dione 5 (1 mmol), and Amberlyst-15 (100 mg) were stirred in CH3OH (5.0 mL) at 80 C. When the reaction was completed (detected by TLC), the spherical catalyst was separated by a sieve at once under hot condition. Then, the reaction mixture was cooled to room temperature, and solid precipitation occurred. After filtration, the crude product was recrystallized from EtOH and DMF to give pure compound.

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, 6-Chloroisatin, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Niu, Qingqing; Xi, Junhua; Li, Lei; Li, Li; Pan, Chengli; Lan, Meijun; Rong, Liangce; Tetrahedron Letters; vol. 60; 43; (2019);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 59-48-3, name is Indolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of Indolin-2-one

Sodium hydride (9.0 g; 0.2 mol, 60% in mineral oil) was added portion-wise to a solution of oxindole (10.0 g, 75 mmol) in of dry DMF (350 mL). After 15 minutes, the reaction was cooled to 0 C. and 1,4 dibromoethane in 100 mL of dry DMF was added over 15 minutes. The dark brown reaction was allowed to warm to room temperature and stirred overnight. The reaction was diluted with ethyl acetate and water was added. The layers were separated and the organic layer was dried over anhydrous sodium sulfate. The organic layer was filtered, concentrated in vacuo to give 20 g of red oil. The crude product was purified on silica using a stepwise gradient of 10% to 20% ethyl acetate: hexane to afford Spiro[cyclopropane-1,3′-[3H]indol]-2′(1’H)-one (2.3 g, 11%).

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

Reference:
Patent; Wyeth; US2006/30615; (2006); A1;,
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 923590-95-8 as follows. Application In Synthesis of 4-Bromoisoindoline hydrochloride

3. Kumada Coupling of Bromo-Iso-Indole [0258] bromoisoindoline HCl salt (25 g, 106.6 mmol), Pd(OAc)2 (0.199 g, 0.533 mmol), and the ligand (di-tert-butylneopentylphosphonium tetrafluoroborate, 0.325 g, 1.066 mmol). PhMe (toluene) (450 mL, de-oxygenated via sparging with N2) was then added, and the resulting slurry was then cooled to Ti=5 C. using an external bath. Allylmagnesium chloride (1.7 N in THF, 207 mL, 351.8 mmol) was charged to an addition funnel via cannula, and then added at a rate such that Ti<20 C. The resulting solution was then was heated to Ti=45-50 C. [0260] After 16 hours, LC showed >99% conversion of starting material. The reaction was cooled to room temperature, and then was inverse-quenched into 250 mL of 15% aqueous citric acid. The phases were separated, and the aqueous phase containing the product was held while the dark organic phase was rejected. The extractor that contained the aqueous phase was charged with 125 mL of PhMe. The pH of the aqueous phase was adjusted by the addition of 115 mL of NH4OH. The phases were separated, and the organic phase containing the product was held while the aqueous phase was rejected. The organic phase was washed with 20 mL of 15% aqueous NaCl. The PhMe solution was concentrated with azeotrope to a 10 volume solution (KF<2000 ppm H2O). [0261] This PhMe solution of product was transferred to 250 mL flask with overhead stirring. An addition funnel was charged with 17.5 mL of 5.33 M HCl in IPA (5.3 M), which was added slowly over 20 minutes. The resulting slurry was aged for 30 minutes at Ti=40 C., and then was gradually cooled to Ti=20-22 C. over 30 minutes. After aging for 1 hour, the slurry was slowly cooled to Ti=0 C. over 30 minutes by use of an external bath. After 30 minutes, the slurry was filtered. The cake was washed with 16 mL of cold (Ti=-10 vC) 14:2 PhMe:IPA. The cake was then washed with 15 mL of ambient temperature (Ti=22 C.) MTBE. After drying, 7.6 g of allyl isoindoline was isolated as an off white solid. The isolated product assayed for 98.7 wt %. According to the analysis of related databases, 923590-95-8, the application of this compound in the production field has become more and more popular. Reference:
Patent; Chen, Cheng; Kong, Jongrock; Humphrey, Guy; Dolman, Sarah; Li, Hongmei; Tudge, Matthew T.; Yong, Kelvin; Xiang, Bangping; Zacuto, Michael; US2013/274463; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 59-48-3, name is Indolin-2-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. name: Indolin-2-one

To a solution of 1,3-Dihydro-indol-2-one (20 g, 133.15 mmol) in acetonitrile (300 ml) at 0 C. was added NBS (30.76 gm, 173.8 mmol) in several portions and the solution stirred at this temperature for 3 h. Water was added to the reaction mixture, upon which a white solid precipitated. The solid was collected by filtration, washed with hot water and dried under vacuum to obtain compound 5-Bromo-1,3-dihydro-indol-2-one (28 g, 88%).

The synthetic route of Indolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Alam, Muzaffar; Du Bois, Daisy Joe; Hawley, Ronald Charles; Kennedy-Smith, Joshua; Minatti, Ana Elena; Palmer, Wylie Solang; Silva, Tania; Wilhelm, Robert Stephen; US2011/71150; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem