Category: indolines-derivatives

Some common heterocyclic compound, 675109-45-2, name is 6-Amino-2,3-dihydro-1H-isoindol-1-one, molecular formula is C8H8N2O, 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: C8H8N2O

To ethyl acetate (10 mL) was added 6-aminoisoindolin-l-one (100 mg, 0.675 mmol), (S)-2-(tert-butoxycarbonylamino)-3-phenylpropanoic acid (179 mg, 0.675 mmol), and DCC (209 mg, 1.012 mmol). The reaction mixture was stirred for 24 h, diluted with ethyl acetate and filtered. The filtrate was washed with 10% citric acid (1 x 10 mL), brine and dried (MgSO4). The crude product was purified by silica gel chromatography (DCM and 0-10%MeOH as eluents) to afford a white foam (0.192 g). The foam was re-dissolved in DCM (5 mL) and to this solution was added TFA (2 mL). After 1 h, the reaction was concentrated to afford 129A (0.29 g, 105%) as a brown oil. LCMS m/z 296.3 [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 675109-45-2, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2008/157162; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 59-48-3, name is Indolin-2-one, A new synthetic method of this compound is introduced below., Recommanded Product: 59-48-3

5-Iodo-2-oxindole 2-Oxindole (82.9 g) was suspended in 630 ML of acetic acid with mechanical stirring and the mixture cooled to 10 C. in an ice water bath.. solid N-iodosuccinimide (175 g) was added in portions over 10 minutes.. After the addition was complete the mixture was stirred for 1.0 hour at 10 C. The suspended solid which had always present became very thick at this time.. The solid was collected by vacuum filtration, washed with 100 ML of 50 % acetic acid in water and then with 200 ML of water and sucked dry for 20 minutes in the funnel.. The product was dried under vacuum to give 93.5 g (36%) of 5-iodo-2-oxindole containing about 5% 2-oxindole by proton NMR.

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; Sugen, Inc.; US6350754; (2002); B2;,
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. 193354-13-1, name is 5-Iodoindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Quality Control of 5-Iodoindolin-2-one

5-Methoxycarbonyl-2-oxindole 5-Iodo-2-oxindole (17 g) was refluxed with 2 g of palladium diacetate, 18.2 g of triethylamine, 150 mL of methanol, 15 mL of dimethylsulfoxide and 2.6 g of DPPP in an atmosphere saturated with carbon monoxide. After 24 hours, the reaction was filtered to remove the catalyst and the filtrate concentrated. The concentrate was chromatographed on silica gel (30% ethyl acetate in hexane). The fractions containing product were concentrated and allowed to stand. The precipitated product was collected by vacuum filtration to give 0.8 g (7%) of the title compound as an off-white solid.

The synthetic route of 193354-13-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUGEN, Inc.; US2003/69421; (2003); A1;; ; Patent; Sugen, Inc.; US6051593; (2000); A;,
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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 65435-04-3 as follows. Safety of 5-(2-Chloroacetyl)indolin-2-one

A suspension of 9.3 g of 5-chloroacetyl-2-oxindole was stirred in 90 ML pyridine at 80 to 90 C. for 3 hours then cooled to room temperature.. The precipitate was collected by vacuum filtration and washed with 20 ML ethanol.. The solid was dissolved in 90 ML 2.5N sodium hydroxide and stirred at 70 to 80 C. for 3 hours.. The mixture was cooled to room temperature and acidified to PH 2 with 0.5 N hydrochloric acid.. The precipitate was collected by vacuum filtration and washed thoroughly with water to give crude 5-carboxy-2-oxindole as a dark brown solid.. After standing overnight the filtrate yielded 2 g of 5-carboxy-2-oxindole as a yellow solid.. The crude dark brown product was dissolved in hot methanol, the insoluble material removed by filtration and the filtrate concentrated to give 5.6 g of 5-carboxy-2-oxindole as a brown solid.. The combined yield was 97%.

According to the analysis of related databases, 65435-04-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sugen, Inc.; US6350754; (2002); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 6872-06-6, These common heterocyclic compound, 6872-06-6, name is 2-Methylindoline, 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.

2-methylindoline (3.26 g, 24.5 mmol) and hexane (0.536 M, 45.7 ml) were placed in a 100 ml Schlenk flask. At -20 C, n-BuLi (1.1 eq, 10.8 ml) was added and allowed to stand at room temperature overnight. Filtered through glass frit (G4) and vacuum dried to obtain phosphine-amine lithium. The phosphine-amine lithium (3.37 g, 24.2 mmol) was added to diethyl ether (0.423 M, 57.3 ml) in a 250 ml Schlenk flask and CO2 bubbling was added at -78 C for 1 hour. THF (1.1 eq, 2.16 ml) and t-BuLi (1.1 eq, 15.7 ml) were added at -20 C and kept at this temperature for 2 hours. IPr2PCl (0.85 eq, 3.14 g) and diethyl ether (0.359 M, 57.3 ml) were added at the same temperature and maintained at the same temperature for 1 hour. After slowly reacting at room temperature overnight, 50 ml of distilled water was added at 0 C, and the mixture was stirred at room temperature for 30 minutes. Work-up with diethyl ether, drying over MgSO4, and then red oil was obtained in 2.23 g, 37% yield via hexane, diethyl ether 50: 1 column

The synthetic route of 6872-06-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LG CHEM, LTD.; JANG, Jae Kwon; KIM, Seul Ki; PARK, In Sung; LEE, Eun Jung; LEE, Choong Hoon; HAN, Ki Won; HAN, Hyo Jung; (20 pag.)KR2017/68330; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

897957-06-1, name is 6-Bromo-1-methylindolin-2-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. SDS of cas: 897957-06-1

A solution of {S)-tert-hvXy 4-(l-amino-l-oxo-3-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 200 mg) and 6-bromo-l-methylindolin-2-one (87 mg) in acetonitrile (5 mL) was treated with potassium carbonate (107 mg) and purged with nitrogen. 1,1 bis(Di-tert- butylphosphino)ferrocene palladium dichloride (15 mg) was added and the reaction stirred under reflux under nitrogen for 4 h and then evaporated in vacuo. The residue was partitioned between water (40 mL) and ethyl acetate (40 mL). The aqueous was further extracted with ethyl acetate (40 mL) and the combined organic extracts were dried over magnesium sulfate and evaporated in vacuo. The crude product was purified by flash silica chromatography eluting with ethyl acetate. Pure fractions were evaporated to dryness to afford the sub-titled compound (45 mg).1H NMR (399.824 MHz, CDCl3) delta 7.54 (d, 2H), 7.32 – 7.28 (m, 3H), 7.22 (d, IH), 6.97 (s, IH), 6.88 – 6.80 (m, IH), 6.49 (d, IH), 5.27 (s, IH), 4.90 (s, IH), 4.80 (q, IH), 3.89 – 3.82 (m, IH), 3.69 – 3.62 (m, IH), 3.60 – 3.48 (m, 4H), 3.32 – 3.18 (m, 5H), 2.33 – 2.24 (m, IH), 1.92 – 1.76 (m, 2H), 1.35 (s, 9H).m/e (Multimode+) 437 [M+2H-BOC]+

The synthetic route of 897957-06-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; FORD, Rhonan; METE, Antonio; MATHER, Andrew; MILLICHIP, Ian; WO2010/128324; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 667463-64-1, 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 667463-64-1 as follows.

General procedure: Step 1: To a 250 mL flask equipped with a silicone oil bubbler was added commercially available isatin (7.7 g, 50 mmol) and anhydrous DMF (80 mL). the mixture was cooled down to 0 oC. To this solution was added NaH (1.32 g, 55 mmol), followed by the addition of CH3I in 15 min. Upon completion of the reaction (monitored by TLC), the mixture was diluted with saturated NH4Cl solution and extracted with ethyl acetate. The organic layer was washed with water, dried over Na2SO4, filtered, and concentrated to yield the crude N-methylindoline-2, 3-dione, which was used directly in the next step. Step 2: The N-methylindoline-2, 3-dione (7.58 g, 47 mmol) was refluxed in NH2·NH2-H2O ( 35 %) for 1h. Then the mixture was cooled to rt. The crude product was extracted with ethyl acetate. The combined organic layer was then dried over Na2SO4, purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 10:1). 1-Methylindolin-2-one was obtained as a pink solid.

According to the analysis of related databases, 667463-64-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Zhao, Jian-bo; Ren, Xinfeng; Zheng, Bu-quan; Ji, Jian; Qiu, Zi-bin; Li, Ya; Journal of Fluorine Chemistry; vol. 215; (2018); p. 44 – 51;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 5181-35-1, name is 2-(2-Bromoethoxy)isoindoline-1,3-dione, molecular formula is C10H8BrNO3, 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. Product Details of 5181-35-1

To a solution of 2-(2- bromoethoxy)isoindoline- l,3-dione (5 g, 1.85 mmol, product from step 1 of preparation 10) and lH-tetrazole (1.3 g, 1.85 mmol) in dimethylformamide (25 ml) was added cesium carbonate (6.0 g, 1.85 mmol) in a lot wise under stirring at room temperature. The progress of reaction was monitored by performing thin layer chromatography using mixture of acetone and hexane (3.5:6.5) as solvent. After 16 hours the completion of the reaction was confirmed by thin layer chromatography. The reaction mixture was slowly poured into chilled water (200 ml) under stirring. After stirring for 30 minutes, the precipitates formed were filtered and washed with water (50 ml). The solid compound was dried at 40 C for 2 hours under high vacuum to provide 3.2 g of a mixture of 2-[2-(lH-tetrazol- l-yl)ethoxy]- lH-isoindole- l,3(2H)-dione and 2-[2-(2H-tetrazol-2- yl)ethoxy]- lH-isoindole- l,3(2H)-dione in 66% yield. Analysis: Mass: 260 (M+l) for Molecular weight: 259 and for Molecular formula: C11H9N5O3; To a flask containing mixture of 2-[2-(lH-tetrazol- l-yl)ethoxy]- lH-isoindole- l,3(2H)- dione and 2-[2-(2H-tetrazol-2-yl)ethoxy]- lH-isoindole- l,3(2H)-dione (3.0 g, 1.15 mmol, product from step 1) in dichloromethane (30 ml) was added hydrazine hydrate (0.870 ml, 1.73 mmol) at 25-30 C under stirring and continued stirring for 2 hours. The progress of reaction was monitored by thin layer chromatography. After complete conversion, the unwanted solid was filtered out and washed with dichloromethane (12 ml). The filtrate was concentrated at 40 C under high vacuum to obtain 1.5 g of crude mixture of l-[2-(aminooxy)ethyl]- lH-tetrazole and 2-[2-(aminooxy)ethyl]- 2H-tetrazole (about 100 % yield) and used without further purification in the next step.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5181-35-1, its application will become more common.

Reference:
Patent; WOCKHARDT LIMITED; TADIPARTHI, Ravikumar; PATIL, Vijaykumar Jagdishwar; DEKHANE, Deepak; SHAIKH, Mohammad Usman; BIRAJDAR, Satish; DOND, Bharat; PATEL, Mahesh Vithalbhai; (100 pag.)WO2017/81615; (2017); A1;,
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. 88150-75-8, name is Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate

Preparation of ETHYL 2-(2-CHLOROBENZYLIDINE)-4-[2-(PHTHALIMIDE) ETHOXY] ACETOACETATE (XV : A 250 mL two-necked flask, equipped with a magnetic stirring bar and thermometer was charged with 10 g of ethyl 4- [2- (phthalimido) ethoxy] acetoacetate and 3.96 g 2- chlorobenzaldehyde and 100 mL isopropanol under nitrogen atmosphere. To the resulting mixture was added 0.188 ML of acetic acid and 0.223 ML pyrolidine. The reaction mixture was heated to 37 C and stirred at this temperature for 5 hours. The solvent was removed in vacuo and the residue was dissolved in 100 ML of methylene chloride. The resulting solution was washed with 100 mL of sat. NAHCO3 and 100 mL of water, dried over 5 G OF MGS04. MGS04 was filtered off, the filtrate was concentrated in vacuo. The residue was purified by flash chromatography using ethyl acetate/hexane (20/80) as an eluent to give 7.72 g of ethyl 2- (2-CHLOROBENZYLIDINE)-4- [2- (PHTHALIMIDE) ethoxy] acetoacetate as an light brown oil (yield 56%, rel. compound purity > 98%). 1H-NMR (CDCL3) No. 7.89 (s, 1H), 7.78 (dd, 2H), 7.69 (dd, 2H), 7.35 (M, 1H), 7.28 (M, 2H), 7.17 (M, 1H), 4.44 (s, 2H), 4.05 (Q, 2H), 3.76 (T, 2H), 3.64 (t, 2H), 1.20 (t, 3H). 13C-NMR (CDCI3) 6 203. 2,168. 4,164. 0,140. 0,134. 0,133. 9,132. 3,131. 5, 130.4, 129.8, 127.3, 126.8, 123.4, 77.7, 68.5, 62.0, 37.4, 14.3.

The synthetic route of 88150-75-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EOS ECZACIBASI OZGUN KIMYASAL URUNLER SANAYI VE TICARET A.S.; WO2004/58711; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 356068-93-4, 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. 356068-93-4 name is (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, 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.

To a stirred solution of compound 1 (0.5 g, 1.67 mmol) in DMF (35 rnL) at room temperature was added etaOBt (1.02 g, 7.52 mmol), triethylamine (2.12 mL, 15.03 mmol), ECDIetaC1 (1.44 g, 1.52 mmol) and methyl 6-aminohexanate hydrochloride(0.91 g, 5.0 mmol) successively. The mixture was stirred for 24 h at room temperature and then was diluted with water (20 mL), brine (20 mL) and saturated bicarbonate solution (20 mL) and the peta of solution was adjusted to 11-12 with 10 M NaOH. The mixture was filtrated and the resulting solid was washed with water and dried to obtain crude yellow solid product 110-4 (0.47 g, 65.8%). LCMS: m/z 428(M+1), 1H NMR(DMSO-J6) deltal.33 (m, 2eta), 1.54 (m, 4H), 2.32 (t, 2H), 2.42(s, 3H), 2.50(s, 3H), 3.20( t, 2H), 3.59 (s, 3H), 6.85 (m, 2H), 7.60 (t, IH), 7.69 (s, IH), 7.71 (m, IH), 10.88 (s, IH), 13.67 (s, IH).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; CURIS, INC.; WO2008/33747; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem