Category: 3676-85-5

Electric Literature of 3676-85-5, These common heterocyclic compound, 3676-85-5, name is 5-Aminoisoindoline-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.

A mixture of the appropriate amine (1 mmol) and the appropriate benzyl bromide (1 mmol) inDMF (0.5 M) was stirred at 60 C until completion of the reaction (up to 40 hours). The reactionmixture was quenched with sat. NaHCO3 and extracted with EtOAc. Crude material was purified by automated flash chromatography (EtOAc:hexanes mixture) to give the desired compound in 12-20% yield; ?H NIVIR (400 MHz,DMSO) 10.81 (s, 1H), 7.64 (d, J= 8.5 Hz, 2H), 7.53 (d, J= 8.5 Hz, 1H), 7.12 (s, 1H), 7.02 (d, J= 2.1 Hz, 1H), 6.95 (dd, J= 8.5, 2.1 Hz, 1H), 4.49 (s, 2H). ?3C NIVIR (101 1VIHz, DMSO) 170.03(s), 169.78 (s), 161.37 (d, J= 250.6 Hz), 154.06 (s), 136.95 (s), 136.83 (s), 135.86 (s), 130.28 (s),125.00 (s), 119.02 (s), 117.02 (s), 116.77 (s), 42.79 (s).

Statistics shows that 5-Aminoisoindoline-1,3-dione is playing an increasingly important role. we look forward to future research findings about 3676-85-5.

Reference:
Patent; THE CENTRE FOR DRUG RESEARCH AND DEVELOPMENT; THE UNIVERSITY OF BRITISH COLUMBIA; ROBERGE, Michel; BARADARAN-HERAVI, Alireza; BALGI, Aruna D.; ZIMMERMANN, Carla D.; KRAUSE, Alexandra; PFEIFER, Thomas Arthur; JAQUITH, James Brian; TAN, Jason Samuel; SHIDMOOSSAVEE, Fahimeh S.; ARNS, Stephen Paul; BAUDELET, Davy Jeremy; (354 pag.)WO2017/49409; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

3676-85-5, name is 5-Aminoisoindoline-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. category: indolines-derivatives

A solution of 400 mg (1.44 mM) of 4-chloro-6,7-diethoxy-quinoline-3-carbonitrile and 305 mg (1.88 mM) of 4-Aminophthalimide in 10 ml of ethanol was refluxed for 3 hours. To the warm solution was added 1 ml of 1M sodium carbonate and the sample was heated for 5 minutes at 100C, then poured into 300 ml of ice water. The solid was collected, washed with water followed by ether and dried under vacuum at 80C to yield 348 mg of 4-(1,3-Dioxo-2,3-dihydro-1H-isoindol-5-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile as a yellow solid: mass spectrum (electrospray, m/e): M+H 402.9, mp = 248-251C.

The synthetic route of 3676-85-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Wyeth Holdings Corporation; EP1117659; (2003); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 3676-85-5, A common heterocyclic compound, 3676-85-5, name is 5-Aminoisoindoline-1,3-dione, molecular formula is C8H6N2O2, 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 mixture of 1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)piperidine-3-carboxylic acid (500 mg, 1.26 mmol), 5-aminoisoindoline-1,3-dione (250 mg, 1.51 mmol) and pyridine (10 mL) was stirred at 0 C. for 2 h. POCl3 (20 drops) was added and stirred for 10 mins, then water (5 mL) was added and the mixture extracted with ethyl acetate (10 mL). The organic layer was washed with brine (10 mL), then dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by prep-HPLC (Gemini 5u C18 150¡Á21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% TFA, v/v) in a linear fashion over 9 min) to give the product. HCl (1 mL) was added and then the mixture concentrated in vacuo to give 1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(1,3-dioxoisoindolin-5-yl)piperidine-3-carboxamide hydrochloride (10 mg, 2%). 1H NMR (300 MHz, DMSO): delta 11.23 (s, 1H), 10.65 (s, 1H), 10.21 (s, 1H), 8.15 (s, 2H), 7.98 (s, 1H), 7.86 (d, 1H, J=8.4 Hz), 7.77 (d, 1H, J=7.8 Hz), 7.43 (d, 1H, J=8.1 Hz), 6.93 (d, 1H, J=8.1 Hz), 4.29 (d, 1H, J=11.7 Hz), 4.14 (d, 1H, J=12.3 Hz), 3.91 (s, 3H), 7.56 (s, 3H), 3.23-3.02 (m, 2H), 2.73 (s, 1H), 2.10-2.06 (s, 1H), 1.82-1.75 (m, 3H). LC-MS: [M+H]+, 543, tR=1.406 min, HPLC: 98.08% at 214 nm, 98.69% at 254 nm, tR=5.25 min.

The synthetic route of 3676-85-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hoffmann-La Roche Inc.; Hermann, Johannes Cornelius; Kuglstatter, Andreas; Lucas, Matthew C.; Padilla, Fernando; Wanner, Jutta; Zhang, Xiaohu; US2013/109661; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 3676-85-5, 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 3676-85-5 as follows.

Example 82 N-(2-Chlorobenzyl)-N’-(1,3-dioxo-2,3-dihydro-1H-5-isoindolyl)urea Diphenylphosphoryl azide (165 mg, 0.60 mmol, 1.2 eq) and triethylamine (61 mg, 0.60 mmol, 1.2 eq) were added to a solution of 2-chlorophenylacetic acid (85 mg, 0.50 mmol) in toluene, and the mixture was stirred at 110C for 60 min. Thereafter, 4-aminophthalimide (81 mg, 0.50 mmol, 1.0 eq) and a minor amount of DMF were added thereto, and the mixture was stirred at 110C for 2 hr. After the completion of the reaction, water and ethyl acetate were added thereto, and the precipitated crystal was collected by filtration and was washed with ethyl acetate to give the title compound as a crystal (37 mg, 22.6%). MS m/z: 329 1H-NMR delta: 4.40 (2H, d, J = 5.61 Hz), 6.94 (1H, t, J = 5.98 Hz), 7.28 – 7.38 (2H, m), 7.41 (1H, dd, J = 1.71, 7.56 Hz), 7.46 (1H, dd, J = 1.71, 7.56 Hz), 7.61 (1H, dd, J = 1.83, 8.17 Hz), 7.68 (1H, d, J = 8.54 Hz), 8.01 (1H, d, J = 1.46 Hz), 9.42 (1H, s), 11.08 (1H, s)

According to the analysis of related databases, 3676-85-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; KIRIN BEER KABUSHIKI KAISHA; EP1256574; (2002); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 3676-85-5, name is 5-Aminoisoindoline-1,3-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 3676-85-5, Safety of 5-Aminoisoindoline-1,3-dione

6: A suspension of 4-amino-phthalimide 5 (6.48 g, 39.9 mmol) in hydrochloric acid (18%, 120 mL) was cooled to 0 C. A solution of sodium nitrite (3.25 g, 47.2 mmol) in H2O (8.0 mL) was added dropwise. The resulted yellow solution was stirred at 0 C for 1 h. A suspension of CuCl (5.90 g, 59.9 mmol) in H2O (8.0 mL) was added to the above solution slowly. The mixture was stirred at 0 C for 3 h and further stirred at 50 C for 1 h. The precipitate was collected by filtration washed by water, dried in vacuum affording a light yellow solid 6 (4.90 g, 68% yield). 1H NMR (DMSO-d6): delta (ppm) 11.50 (s, 1H, CONHCO), 7.88 (d, 1H, 1.6 Hz), 7.87-7.82 (m, 2H). 13C NMR (DMSO-d6): delta (ppm) 168.23, 167.83, 138.99, 134.57, 134.00, 131.12, 124.64, 122.95.

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, 5-Aminoisoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Song, Xiaoyu; Zhao, Jing; Zhang, Wandong; Chen, Long; Chinese Chemical Letters; (2018); p. 331 – 335;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 3676-85-5, 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 3676-85-5 as follows.

6: A suspension of 4-amino-phthalimide 5 (6.48 g, 39.9 mmol) in hydrochloric acid (18%, 120 mL) was cooled to 0 C. A solution of sodium nitrite (3.25 g, 47.2 mmol) in H2O (8.0 mL) was added dropwise. The resulted yellow solution was stirred at 0 C for 1 h. A suspension of CuCl (5.90 g, 59.9 mmol) in H2O (8.0 mL) was added to the above solution slowly. The mixture was stirred at 0 C for 3 h and further stirred at 50 C for 1 h. The precipitate was collected by filtration washed by water, dried in vacuum affording a light yellow solid 6 (4.90 g, 68% yield). 1H NMR (DMSO-d6): delta (ppm) 11.50 (s, 1H, CONHCO), 7.88 (d, 1H, 1.6 Hz), 7.87-7.82 (m, 2H). 13C NMR (DMSO-d6): delta (ppm) 168.23, 167.83, 138.99, 134.57, 134.00, 131.12, 124.64, 122.95.

According to the analysis of related databases, 3676-85-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Song, Xiaoyu; Zhao, Jing; Zhang, Wandong; Chen, Long; Chinese Chemical Letters; (2018); p. 331 – 335;,
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 3676-85-5 as follows. Recommanded Product: 5-Aminoisoindoline-1,3-dione

A mixture of l-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[l ,2-b]pyridazin-6-yl) piperidine-3- carboxylic acid (500 mg, 1.26 mmol), 5-aminoisoindoline-l ,3-dione (250 mg, 1.51 mmol) and pyridine (10 mL) was stirred at 0C for 2 h. POCI3 (20 drops) was added and stirred for 10 mins, then water (5 mL) was added and the mixture extracted with ethyl acetate (10 mL). The organic layer was washed with brine (10 mL), then dried over Na2S04, filtered and concentrated in vacuo The crude product was purified by prep-HPLC (Gemini 5u CI 8 150×21.2 mm; inject volume: 3mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20 % acetonitrile/80 % water (0.1 % TFA, v/v) initially, proceeding to 50 % acetonitrile/50 % water (0.1 % TFA, v/v) in a linear fashion over 9 min) to give the product. HC1 (1 mL) was added and then the mixture concentrated in vacuo to give l-(8-(5,6-dimethoxypyridin-2- ylamino)imidazo[l ,2-b]pyridazin-6-yl)-N-(l ,3-dioxoisoindolin-5-yl)piperidine-3-carboxamide hydrochloride (10 mg, 2 %). 1H NMR (300 MHz, DMSO): delta 1 1.23 (s, 1H), 10.65 (s, 1H), 10.21 (s, 1H), 8.15 (s, 2H), 7.98 (s, 1H), 7.86 (d, 1H, J = 8.4 Hz), 7.77 (d, 1H, J= 7.8 Hz), 7.43 (d, 1H, J = 8.1 Hz), 6.93 (d, 1H, J = 8.1 Hz), 4.29 (d, 1H, J = 1 1.7 Hz), 4.14 (d, 1H, J = 12.3 Hz), 3.91 (s: 3H), 7.56 (s, 3H), 3.23 – 3.02 (m, 2H), 2.73 (s, 1H), 2.10 – 2.06 (s, 1H), 1.82 – 1.75 (m, 3H). LC- MS : [M+H]+, 543, tR = 1.406 min, HPLC: 98.08 % at 214nm, 98.69 % at 254nm, tR = 5.25 mm.

According to the analysis of related databases, 3676-85-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HERMANN, Johannes Cornelius; KUGLSTATTER, Andreas; LUCAS, Matthew C.; PADILLA, Fernando; WANNER, Jutta; ZHANG, Xiaohu; WO2013/64445; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 3676-85-5, These common heterocyclic compound, 3676-85-5, name is 5-Aminoisoindoline-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.

Example 50 1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1,3-dioxoisoindolin-5-yl)piperidine-3-carboxamide Procedure: To a solution of 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid (50 mg, 0.12 mmol) and 5-aminoisoindoline-1,3-dione (19 mg, 0.12 mmol) in pyridine (8 mL) was added POCl3 (0.3 mL, 3.23 mmol) at 0 C., the reaction mixture was stirred at room temperature for 4 hours, a sat.NaHCO3 solution was added slowly, the solvent was removed in vacuo, water (5 mL) and methanol (2 mL) were added. The precipitate was collected by filtration and washed with water (5 mL) and methanol (5 mL) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1,3-dioxoisoindolin-5-yl)piperidine-3-carboxamide (27 mg, 40.0%) as an orange solid. 1H NMR (300 MHz, DMSO): delta 11.20 (s, 1H), 10.59 (s, 1H), 9.64 (s, 1H), 8.83 (s, 1H), 8.13 (s, 1H), 7.86-7.73 (m, 2H), 7.63 (s, 1H), 7.38-7.29 (m, 1H), 6.78 (s, 1H), 4.77 (d, 1H, J=12.0 Hz), 4.62 (d, 1H, J=12.3 Hz), 3.66 (s, 3H), 3.61 (s, 3H), 3.16-2.94 (m, 2H), 2.60-2.55 (m, 1H), 2.04-2.01 (m, 1H), 1.76-1.72 (m, 2H), 1.52-1.41 (m, 1H). LC-MS: 560 [M+H]+, tR=1.49 min. HPLC: 99.49% at 214 nm, 99.47% at 254 nm, tR=5.33 min.

The synthetic route of 3676-85-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hermann, Johannes Cornelius; Lowrie, JR., Lee Edwin; Lucas, Matthew C.; Luk, Kin-Chun Thomas; Padilla, Fernando; Wanner, Jutta; Xie, Wenwei; Zhang, Xiaohu; US2012/252777; (2012); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 3676-85-5, name is 5-Aminoisoindoline-1,3-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 3676-85-5, category: indolines-derivatives

The synthesis of bromoacetal 6 from phthalimide (7) is shown in FIG. 11. Based on reactions described in the literature, these transformations were carried out on large scale, and some steps were improved. Nitration of 200 g of phthalimide (7) gives 146 g of 5-nitrophthalimide (8). Reduction of 8 by catalytic hydrogenation, according to the literature procedure, is a bottleneck in the synthesis because of the large volume of solvent needed. With a 2 L Parr hydrogenator pressure vessel, 30 g of 8 is converted to 25 g of amine 9. The next step is also a reduction; aminophthalide 10 is obtained quantitatively from 9 by copper-catalyzed reaction with zinc in aqueous base. Steps b and c could be combined by treating 8 with zinc dust and copper(II) sulfate in 2 M aq. sodium hydroxide. This variation, which is not shown in FIG. 11, removes the bottleneck, potentially allowing 100 g of 10 to be prepared in one step from 146 g of 9. The reaction conditions for the steps shown in FIG. 11 are as follows: a) HNO3, H2SO4, 0 C., 56% ; b) 5% Pd/C, H2, EtOAc, 97% ; c) Zn, CuSO4, 6 M NaOH, 5 C. then heated at 70-80 C. 16 h, 100% ; d) NaNO2, 4 M HBr, followed by CuBr at 0 C.; e) DIBAL, toluene, -42 C.; f) BF3 OEt2, MeOH, RT.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Aminoisoindoline-1,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; Bell, Thomas W.; Cline, Joseph I.; Cremo, Christine R.; Gillett, Stephen L.; Frederick, John H.; US2011/77394; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 3676-85-5, 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. 3676-85-5, name is 5-Aminoisoindoline-1,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

10 parts of 4-aminophthalimide and 11 parts of cyanuric chloride were added to 100 parts of nitrobenzene, and the mixture was heated at 100 to 110 C. for 5 hours. After cooling it was filtered and washed with methanol and water. And dried at 80 C. to obtain 17 parts of the intermediate (2) represented by the formula (2).

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

Reference:
Patent; Dainichiseika Color & Chemicals Mfg. Co., Ltd.; Iguchi, Kazunori; Yanagimoto, Hiromitsu; (18 pag.)JP5823432; (2015); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem