Category: indolines-derivatives

These common heterocyclic compound, 7147-90-2, name is 5-Chloroisoindoline-1,3-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. Formula: C8H4ClNO2

N-4-methylphenylglycine ethyl ester (0.3 mmol) under air atmosphere,A phthalimide compound (0.2 mmol) and cuprous chloride (0.02 mmol) were placed in a dry reaction tube with stirring magnets.Then, an acetonitrile solvent (2 mL) was added to the test tube, and the reaction tube was reacted in an air atmosphere at 60 C for 24 hours.After the reaction is completed, it is cooled to room temperature, and the solvent is distilled off under reduced pressure using a rotary evaporator.The residue is purified by column chromatography to obtain a pure pale yellow solid 3n.The yield was 67%.

The synthetic route of 5-Chloroisoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Donghua University Of Science And Technology; Zhu Zhiqiang; Xiao Lijin; Xie Zongbo; Yue Changgao; (12 pag.)CN108623514; (2018); A;,
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Synthetic Route of 5332-26-3, These common heterocyclic compound, 5332-26-3, name is 2-(Bromomethyl)isoindoline-1,3-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.

Step 1. Dimethyl (phthalimidomethyl)phosphonate (ii). A mixture of N-(bromomethyl) phthalimide (i) (10.43 g, 43.46 mmol) and trimethyl phosphite (5.93 g, 47.80 mmol) was heated at reflux in xylene (20 mL) for 6 h. The reaction mixture was then cooled to room temperature and concentrated. Crystallization from CHCl3-hexane gave (ii) (7.60 g, 65%) as a white solid: 1H NMR (300 MHz, CDCl3) deltaH 3.84 (d, JH,P=10.8 Hz, 6 H), 4.12 (d, J=11.4 Hz, 2 H), 7.76 (m, 2 H), 7.87 (m, 2 H).

The synthetic route of 5332-26-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Besterman, Jeffrey M.; Rahil, Jubrail; Vaisburg, Arkadii; US2004/29836; (2004); A1;,
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Synthetic Route of 496-12-8, These common heterocyclic compound, 496-12-8, name is Isoindoline, 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.

Example 343 (BVT074103); 2-anilino-5-[2-(1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-1, 3-thiazol-4 (5H)-one ;(2-anilino-4-oxo-4, 5-dihydro-1, 3-thiazol-5-yl) acetic acid (25 mg, 1 eq) was dissolved in DCM (1 mL) and 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (EDC, 29 mg, 1.5 eq), 1-hydroxybenzotriazole hydrate (HOBt, 20 mg, 1.5 eq), and N- methylmorpholine (NMM, 44 u. L, 4 eq) were added sequentially. After 10 min stirring at room temperature isoindoline (13 pL, 1.1 eq) was added and the reaction mixture was stirred overnight at room temperature H,, O (5 mL) and DCM (5 mL) was added, the organic layer separated on a 1-PS syringe and concentrated. Purified by flashtube DCM- MeOH (14: 1). 17 mg, yield 47%. 1H NMR (400 MHz, CHLOROFORM-D) 8 ppm 2.09-2. 45 (m, 2 H), 4.19-4. 42 (m, 1 H), 4.53-4. 77 (m, 4 H), 7.01-7. 22 (m, 7 H), 7.30-7. 42 (m, 2 H). MS [M+H] + m/z = 352.

Statistics shows that Isoindoline is playing an increasingly important role. we look forward to future research findings about 496-12-8.

Reference:
Patent; BIOVITRUM AB; WO2005/75471; (2005); A2;,
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446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, 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: 446292-08-6

Reference example 1: Synthesis of (S)-4-{4-[5-(aminomethyl)-2-oxo-l,3-oxazolidin- 3-yl]phenyl}morpholin-3-one sulfate (2: 1) [compound IV-sulfate (2: 1)]26.07 g (61.9 mmol) of (5)-2-({2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-l,3- oxazolidin-5-yl}methyl)-lH-isoindole-l,3(2H)-dione (compound III, obtained from compound II following the process disclosed in the ‘ 823 patent) were suspended in 196 mL of ethanol. 24.0 mL (278.4 mmol) of 40% w/w aqueous methylamine were added to the suspension, and the resulting mixture was heated to 60-65C and maintained at this temperature for about 2.5 hours. The content of unreacted compound III was checked to be below 5% by TLC. At this point, 75.1 g (178.2 mmol) of 20% w/w aqueous sulfuric acid were added over the reaction mixture while keeping the temperature above 60 C. Precipitation was observed during the addition. The resulting suspension was heated to 70-75 C and stirred at this temperature for about 1 hour, then cooled down to 20-25 C and stirred at this temperature for about 1 hour. Subsequently, the suspension was filtered and the collected solid was washed with 26.1 mL of ethanol followed by 26.1 mL of acetone to give 18.4 g of wet (,S)-4-{4-[5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one sulfate (2: 1) as a white solid. Estimated dry mass: 17.4 g. Yield: 82.7%.

The synthetic route of 446292-08-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDICHEM S.A.; MANGION, Bernardino; DURAN LOPEZ, Ernesto; WO2012/35057; (2012); A2;,
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Electric Literature of 14192-26-8, A common heterocyclic compound, 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, molecular formula is C10H9NO3, 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.

To a stirred solution of methyl 2-oxoindoline-6-carboxylate (10.0 g, 52.33 mmol) in 1,4-dioxane (500 mL) was added selenium dioxide (27.9 g, 261.68 mmol) and the resulting reaction mixture was stirred vigorously at 100 C for 1 h. After completion of the reaction, the reaction mixture was diluted with EtOAc and water and filtered through a bed of celite. The filtrate layers were separated and the organic layer was washed with water and brine, dried over anhydrous Na2S04 and then evaporated under reduced pressure to provide the crude product. This was purified by Comb1-flash using 50% EtOAc in hexanes as eluent to afford methyl 2,3-dioxoindoline-6-carboxylate (3.5 g, 17.06 mmol, 34% yield) as a light yellow solid.

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; CURADEV PHARMA LIMITED; BANERJEE, Monali; MIDDYA, Sandip; BASU, Sourav; YADAV, Dharmendra; GHOSH, Rajib; PRYDE, David; SHRIVASTAVA, Ritesh; SURYA, Arjun; (190 pag.)WO2018/234807; (2018); A1;,
Indoline – Wikipedia,
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Some common heterocyclic compound, 20780-72-7, name is 4-Bromoisatin, molecular formula is C8H4BrNO2, 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: 4-Bromoisatin

To 4-bromoindoline-2,3-dione (8.94 g, 39.6 mmol) was added 1.0 M sodium hydroxide (40 mL, 120 mmol) to give a dark brown mixture. The mixture was heated to 80 °C then 20percent hydrogen peroxide (9 mL, 88 mmol) was added slowly over 15 min (caution: a strong exotherm was observed upon reagent addition). The mixture was then stirred at 80 °C for lh. After this time, the mixture was cooled in an ice bath to ~10 °C and then concentrated to a residue. HC1 was added cautiously to the residue until the pH of the mixture was 4-5. Once at the prescribed pH, the mixture was then concentrated to dryness and MeOH (150 ml) was added. The resulting suspension stirred for 15 min and then filtered. The filtrate wasconcentrated to dryness and dried under vacuum for 14 h to yield 2-amino-6- bromobenzoic acid (9.18 g) as a brown solid. 3/4 NMR (400 MHz, DMSO-d6) delta ppm 6.72 (1 H, t, J=7.91 Hz), 6.60 (1 H, dd, J=7.78, 1.00 Hz), 6.52 (1 H, dd, J=7.91, 1.13 Hz). LCMS Method D: retention time 0.68 min, [M+l] 200.0.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 20780-72-7, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; JOHNSON, James A.; LLOYD, John; FINLAY, Heather; JIANG, Ji; NEELS, James; DHONDI, Naveen Kumar; GUNAGA, Prashantha; BANERJEE, Abhisek; ADISECHAN, Ashokkumar; WO2011/28741; (2011); A1;,
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Synthetic Route of 13861-75-1, 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. 13861-75-1, name is Spiro[cyclopropane-1,3′-indolin]-2′-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

The spiro [cyclopropane-1,3′-indol] -2′-one 63a (3g, 18.8mmol) was dissolved in 3mL of acetonitrile at room temperature was added 2-bromo-1,1-dimethoxyethane ( 3.34g, 19.7mmol), potassium carbonate (12.25g, 37.6mmol), potassium iodide (10mg), the reaction was stirred for 16 hours at room temperature. The reaction solution was concentrated under reduced pressure, the reaction solution was added 100mL of water, extracted with ethyl acetate (100mL × 2), and the combined organic phase was washed with water (100mL × 3), washed with saturated sodium chloride solution (100mL × 2), dried over anhydrous dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. By column chromatography (PE: EtOAc = 4: 1) to give purified 1 ‘- (2,2-dimethoxy-ethyl) spiro [cyclopropane-1,3′-indol] -2′-one 63b (2g, yellow solid), yield: 43.0%.

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, Spiro[cyclopropane-1,3′-indolin]-2’-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Nanjing Mingde New Drug Research And Development Co. Ltd; HE, HAI-YING; SHI, WEI-HUA; JIANG, ZHI-GAN; HAN, LI-XIA; SUN, JI-KUI; LI, JIAN; CHEN, SHU-HUI; (175 pag.)TW2016/5834; (2016); A;,
Indoline – Wikipedia,
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Synthetic Route of 1168150-46-6, These common heterocyclic compound, 1168150-46-6, name is (E)-Methyl 3-(methoxy(phenyl)methylene)-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.

General procedure: A mixture of intermediate (3a, 3b, 6a, 6b, 10a, 10b, 11a-d, and14a-g, 1.5 mmol) and methyl (E)-3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate (1.5 mmol) in methanol (10 mL) wasstirred under reflux for 5-10 h. When TLC showed the completionof the reaction, the solution was cooled to room temperature. Theprecipitate was filtered off to give a crude product, which wasrecrystallized from methanol to provide the target compounds.

Statistics shows that (E)-Methyl 3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate is playing an increasingly important role. we look forward to future research findings about 1168150-46-6.

Reference:
Article; Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang; European Journal of Medicinal Chemistry; vol. 139; (2017); p. 492 – 502;,
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Electric Literature of 912999-79-2, 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. 912999-79-2, name is 5-Chloroisoindoline hydrochloride, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of Compound 151A (340 mg, 2.36 mmol) and 1-(azidomethyl)-4- methoxybenzene (500 mg, 3.07 mmol) in toluene (15 mL) was stirred at 110 C for 48 hours. The reaction mixture was concentrated and purified by column chromatography on silica gel using ethyl acetate- hexane as eluent to afford a Mixture 151B. LC-MS (ESI) m/z: 278 [M+H]._A Mixture 151B (60 mg, 0.217 mmol) and thionyl chloride (0.45 mL) in methylene chloride (10 mL) was stirred at 50 C for 5 hours. The reaction mixture was concentrated to give isic, which was used directly in the next step without further purification.LC-MS (ESI) m/z: 296 [M+H]._ A Mixture 151C (74 mg, 0.2 17 mmol), 5-chloroisoindoline (38 mg, 0.248 mmol), and K2C03 (60 mg, 0.43 5 mmol) in DMF (6 mL) was stirred at 60 C for 5 hours. The mixture was poured into water (100 mL) and extracted with ethyl acetate (100 mL x 3). The combined extracts were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with preparative HPLC to afford a Mixture 151D. LCMS (ESI) m/z: 413 [M+H]t

The chemical industry reduces the impact on the environment during synthesis 5-Chloroisoindoline hydrochloride. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BIOMARIN PHARMACEUTICAL INC.; WANG, Bing; CHAO, Qi; (737 pag.)WO2019/133770; (2019); A2;,
Indoline – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 16800-68-3, name is 1-Acetylindolin-3-one, 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 16800-68-3, 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

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, 1-Acetylindolin-3-one, other downstream synthetic routes, hurry up and to see.

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