Category: indolines-derivatives

Synthetic Route of 19727-83-4, A common heterocyclic compound, 19727-83-4, name is 6-Nitroindoline, molecular formula is C8H8N2O2, 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 A: 6-Nitroindoline (3.0 g, 18.3 mmol) was dissolved in THF (45 mL) and Et3N (3.4 mL, 24.4 mmol) at O0C. Acetyl chloride (1.5 mL, 21 mmol) was added drop wise. The mixture was stirred at room temperature for 30 minutes. The mixture was partitioned between EtOAc and aqueous HCl. The organic layer was dried and concentrated to yield l-acetyl-6-nitroindoline (3.8 g, 100%) as a 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; PTC THERAPEUTICS, INC.; HWANG, Peter Seongwoo; TAKASUGI, James; REN, Hongyu; WILDE, Richard Gerald; TURPOFF, Anthony; AREFOLOV, Alexander; KARP, Gary Mitchell; CHEN, Guangming; CAMPBELL, Jeffrey Allen; WO2006/19831; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 7477-63-6, A common heterocyclic compound, 7477-63-6, name is 7-Chloroisatin, molecular formula is C8H4ClNO2, 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.

In a 100 mL round bottom flask, according to the feed ratio (7-chloroisatin: benzyl alcohol (1:1.5); 7-chloroisatin: malondialdehyde (1:1.2))Add 7-chloroisatin 80 mg (0.44 mmol), benzyl alcohol 71.3 mg (0.66 mmol) and malondialdehyde 38.2 mg (0.53 mmol), respectively.Add a catalytic amount (0.1 times equivalent of 7-chloroisatin) of 001×7 MB, ferrocene and palladium acetate, 50 mL of solvent benzene, heat to 90 ° C, and heat the reaction for 6 hours.The reaction was monitored by thin layer chromatography. After the reaction was completed, the heating was stopped, the condensing device was removed, the mixed system was concentrated under reduced pressure, and purified by column chromatography.The target compound (14) was obtained by drying to give 115.8 mg (yield: 81percent).

The synthetic route of 7477-63-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shaanxi University of Science and Technology; Liang Chengyuan; Tian Danni; Ding Shunjun; Wang Xuechuan; Dong Hao; Wang Qiang; (15 pag.)CN108395438; (2018); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 2436-29-5, 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. 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal, This compound has unique chemical properties. The synthetic route is as follows.

Example 26Synthesis of 2-(3-((7-methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dione (181) To a slurry of 4-(4-amino-6-methoxynaphthalen-2-yl)-N-methylpyrimidin-2-amine (150 mg, 0.42 mmol) in 1,2-dichloromethane (10 ml) was added N,N-diisopropylethylamine (250 mul) followed by acetic acid (0.5 ml), 3-(1,3-dioxoisoindolin-2-yl)propanal (140 mg) and sodium triacetoxyborohydride (200 mg). The mixture was stirred at room temperature for 24 hours before being poured into ethyl acetate (100 ml) washed with water (250 ml) and dried over anhydrous magnesium sulfate. Evaporation to dryness gave a yellow oil which was purified by silica gel chromatography eluting with 40-60% ethyl acetate in hexanes to yield 2-(3-((7-methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dione 181 as a yellow foam (95 mg). 1H NMR (CDCl3) 400 MHz delta 8.34 (d, J=5.2 Hz, 1H), 7.87 (s, 1H), 7.86-7.83 (m, 3H), 7.8 (d, J=8.8 Hz, 1H), 7.75-7.71 (m, 2H), 7.34 (s, 1H), 7.31 (d, J=2.4 Hz, 1H), 7.18 (dd, J=2.4 and 8.8 Hz, 1H), 7.08 (d, J=4.8 Hz, 1H), 5.24 (m, 1H), 4.9 (m, 1H), 4.04 (s, 3H), 3.9 (t, J=6.0 Hz 2H), 3.5 (t, J=6.0 Hz, 2H), 3.11 (d, J=5.2 Hz, 3H), 2.24 (m, 2H), 2.2-2.14 (m, 2H), LCMS m/e 468 (M+H)

The chemical industry reduces the impact on the environment during synthesis 3-(1,3-Dioxoisoindolin-2-yl)propanal. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ArQule, Inc.; US2011/166137; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 350797-56-7, 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. 350797-56-7 name is 3-(7-Cyano-5-(2-nitropropyl)indolin-1-yl)propyl benzoate, 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.

General procedure: Raw materials (II), hydrochloric acid added to the organic solvent, heated to a certain temperature, slowly adding zinc powder in batch, by thin layer chromatography (TLC) or high performance liquid chromatography (HPLC) to the raw material (II) completely react , The filter cake is washed with a solvent to the product (I), and then subjected to separation and purification by conventional means such as concentration, washing, drying,To give the salt of the compound (I), which is obtained by alkalizing the free base of (I).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(7-Cyano-5-(2-nitropropyl)indolin-1-yl)propyl benzoate, and friends who are interested can also refer to it.

Reference:
Patent; Changzhou Ruiming Pharmaceutical Co., Ltd.; Shi Weiming; (5 pag.)CN106928118; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 150544-04-0, A common heterocyclic compound, 150544-04-0, name is 6-Aminoindolin-2-one, molecular formula is C8H8N2O, 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 above compound (2 g) and ethyl 1,3-dioxobenzo[c]azolidine-2-carboxylate (1.1 eq) in THF was refluxed overnight. The reaction was cooled and the precipitate was filtered. The gray solid (2 g) was heated with acetic anhydride (2 eq) in acetic acid (40 ml) at 115° C. overnight. The solvent was evaporated and the product was triturated with 50percent EtOAc/Hexane and filtered to give 1-acetyl-6-(1,3-dioxobenzo[c]-azolidin-2-yl)-2-oxoindoline as a dark gray solid.

The synthetic route of 150544-04-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chen, Guoqing P.; US2004/259916; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 118289-55-7, These common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)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.

88.7 g (0.837 mols, 3.21 molar equivalents) of sodium carbonate, 600 ml of acetonitrile and 66.7 g (0.261 mols, 1.0 molar equivalent) of 3- (1-piperazinyl) -1, 2- benzisothiazole hydrochloride [hydrochloride of the compound of formula (III) ] are added into a beaker –> equipped with a magnetic stirrer. The resulting white suspension is stirred for 10 minutes. At this point 60.0 g (0.261 mols, 1.0 molar equivalent) of 5- (2- chloroethyl) -6-chloro-l, 3-dihydro-indole-2- (2H) -one [compound of formula (II) wherein X is chlorine] and 0.3 g (0.002 mols, 0.008 molar equivalents) of NaI are added. The resulting brown suspension is charged into a 1 L reactor vessel, which is purged with nitrogen and heated to 120-125 C (internal pressure increases to 400-500 kPa) for 25 hours. The reaction is cooled to room temperature, stirred for 30 minutes, filtered and the solid washed with acetonitrile. A wet mixture of zipradisone and inorganic salts is obtained.The resulting wet mixture is stirred with 675 ml of water at reflux temperature for 1 h to remove inorganic salts . The suspension is cooled at room temperature, stirred for 30 minutes and filtered. The solid is washed with water, and 140 g of wet solid (corresponding to 87 g of dry material) are obtained.The wet solid is stirred again with water at reflux temperature for 1 h to remove residual inorganic salts. The suspension is cooled to room temperature, stirred for 30 minutes and filtered. The solid is washed with water, and 170 g of wet solid (corresponding to 81 g of dry- material) are obtained. HPLC analysis reveals a purity of 97.8%.To remove starting materials present in the wet solid obtained in the previous step, it is stirred twice with 400 ml of tetrahydrofuran at reflux temperature. The solution is cooled to room temperature, stirred for 30 –> minutes and filtered. The solid is washed twice with 40 ml of tetrahydrofuran at room temperature and 60 g of wet solid, corresponding to 54.8 g of dry material, are obtained.The solid obtained is ziprasidone base having a purity of 99.4% by HPLC and the global yield from the starting compound (II) or (III) is 51% molar. Potentiometric titration with HClO4: 100.03% Optionally, Ziprasidone base could be converted to ziprasidone hydrochloride.;Example 3. Large scale preparation of ziprasidone baseInto a 100 1 Hastelloy reactor are loaded:- 8 kg (31.3 mols 1.0 molar equivalent) of 3-(l- piperazinyl) -1, 2-benzisothiazole hydrochloride[hydrochloride of compound of formula (III) ] ,- 8.64 kg (37.5 mols, 1.2 molar equivalents) of 5- (2- chloroethyl) -6-chloro-l, 3-dihydro-indole-2- (2H) -one [compound of formula (II) wherein X is chlorine] ,- 10.6 kg (100 mols, 3.20 molar equivalents) of sodium carbonate,- 0.038 kg (0.25 mols, 0.008 molar equivalents) of NaIThe reactor is closed and blanketed with vacuum/nitrogen. Then, 56.3 kg of acetonitrile are loaded and the mixture is stirred for 10 minutes. The reactor is heated to reflux (80-82 C) . Then the reactor is closed and –> continued to be heated up to 120-125 C (internal pressure increases to 300 kPa) . The reaction mixture is kept under these conditions for 25 hours. Then the content is cooled down to room temperature and the solid is centrifuged and washed with 2 x 12 kg of acetonitrile. A wet solid containing ziprasidone base and inorganic salts is obtained.The resulting solid is loaded in a 100 1 Hastelloy reactor. The reactor is blanketed and 52 kg of water are loaded. The suspension is stirred at reflux conditions(80-850C; due to the presence of acetonitrile) for 1 h to remove inorganic salts. The suspension is cooled down to room temperature, stirred for 30 minutes and the solid is centrifuged and washed with 2 x 9 kg of water. 17.97 kg of wet solid are obtained.The wet solid from the previous step is loaded in a 100 1 Hastelloy reactor. The reactor is blanketed and 57 kg of tetrahydrofuran are loaded. The suspension is stirred at reflux conditions for 1 h. The suspension is cooled down to room temperature, stirred for 30 minutes and the solid is filtered through a Nutsche Filter and washed with 2 x 16 kg of tetrahydrofuran. 10.53 kg of wet solid (corresponding to 8.57 kg of dry material) are obtained.The solid obtained is ziprasidone base having a purity by HPLC of 99.2%. The global yield from the starting compound (III) is 66.3% (molar yield) . Optionally, Ziprasidone base could be converted to ziprasidone hydrochloride.Example 4 : Preparation of ziprasidone base –> 13.26 g (0.400 mols, 3.20 molar equivalents) of sodium carbonate, 10.00 g (0.039 mols, 1.0 molar equivalent) of3- (1-piperazinyl) -1, 2-benzisothiazole hydrochloride [hydrochloride of the compound of formula (III)], 10.80 g(0.0469 mols, 1.2 molar equivalent) of 5- (2-chloroethyl) -6-chloro-l, 3-dihydro-indole-2- (2H) -one [compound of formula (II) wherein X is chlorine] and 7.030 g (0.0469 mols, 1.2 molar equivalents) of NaI are added into a 250 ml round bottom, three necked reaction vessel, equi…

The synthetic route of 118289-55-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDICHEM, S.A.; WO2006/34964; (2006); 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. 104618-32-8, name is 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 2-(4-Oxocyclohexyl)isoindoline-1,3-dione

Example 11 3-Amino-6-(N-methylsulphonamidomethyl)-1,2,3,4-tetrahydrocarbazole oxalate Reaction of 4-phthalimidocyclohexanone (0.42 g) with 4-(N-methylsulphonamidomethyl) phenyl hydrazine hydrochloride (0.44 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 (0.15 g), mp 218-222C dec.

According to the analysis of related databases, 104618-32-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SMITHKLINE BEECHAM PLC; EP603432; (1994); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 99365-40-9, 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. 99365-40-9, name is 6-Bromoindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A solution of 28 (3.74 g, 17.64 mmol) in dry THF (150mL) was degassed with N2 for 15 min. The solution was then cooled to-78 C and a solution of NaHMDS (1 M in THF, 88.2 mL) was added dropwise over a10 min period. The reaction was stirred at -78 C for 1 h before adding solid N-benzyl-2-chloro-N-(2-chloroethyl)ethan-1-amine HCl salt (5.20 g, 19.40 mmol) in oneportion. The reaction was stirred at -78 C for 1 h before removing the coldbath and allowing the reaction to warm to rt. Upon reaching rt, the reactionwas heated to 70 C (reflux) for 15 hours. The mixture was cooled to 0 C and asaturated aq. NH4Cl solution (150 mL) was added followed by EtOAc(300 mL) for the workup. The organic layer was separated and the aqueous layerwas extracted twice with EtOAc (50 mL x 2).The organic layers were combined, washed with brine, dried using Na2SO4and evaporated to afford the crude product. This crude product wastriturated using hot petroleum ether to give 29 (6.10 g, 93%) as a pink colored solid.

The synthetic route of 6-Bromoindolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Article; Lotesta, Stephen D.; Marcus, Andrew P.; Zheng, Yajun; Leftheris, Katerina; Noto, Paul B.; Meng, Shi; Kandpal, Geeta; Chen, Guozhou; Zhou, Jing; McKeever, Brian; Bukhtiyarov, Yuri; Zhao, Yi; Lala, Deepak S.; Singh, Suresh B.; McGeehan, Gerard M.; Bioorganic and Medicinal Chemistry; vol. 24; 6; (2016); p. 1384 – 1391;,
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. 32692-19-6, name is 5-Nitroindoline, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C8H8N2O2

General procedure: We described the synthesis of the compound 1 (Table 2) to illustrate the general procedure for TFA accelerated Petasis three-component reaction. The descriptions of the preparations of all reported compounds are in the Supporting information section. To a magnetically stirred mixture of 5-nitroindoline (0.164 g, 1.0 mmol), 4-tolyboronic acid (0.135 g, 1.0 mmol), and glyoxylic acid monohydrate (0.092 g, 1.0 mmol) in CH2Cl2 (5 ml) was added TFA (20 mul). The mixture was stirred at room temperature for 4 h. After the completion of the reaction (TLC monitoring), half of the solvent was evaporated by means of a rotovap. The resulting solid was filtered through a sintered glass funnel. The collected solid was thoroughly washed with petroleum ether and a small amount of ice water (5 ml), and then dried in vacuo at room temperature for 24 h to afford 0.26 g (83.3 %) of 2-(5-nitroindolin-1-yl)-2-(p-tolyl) acetic acid as a light yellow solid.

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 32692-19-6.

Reference:
Article; Zhang, Jing; Yun, Fan; Xie, Rui; Cheng, Chunhui; Chen, Guangyao; Li, Jingxuan; Tang, Pingwah; Yuan, Qipeng; Tetrahedron Letters; vol. 57; 35; (2016); p. 3916 – 3919;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 99365-40-9, 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. 99365-40-9, name is 6-Bromoindolin-2-one, This compound has unique chemical properties. The synthetic route is as follows.

n-Butyllithium (2.25 M in hexane, 130 mL, 259.4 mmol) was added drop wise at -40C to a solution of 6-bromoindolin-2-one (25.0 g, 117.9 mmol) and diisopropylamine (36.54 mL, 259.4 mmol) in THF (500 mL).The mixture was stirred for 45 mm at that temperature, 1,2-dibromoethane (31.0 mL, 353.7 mmol) wasadded drop wise and stirring was continued for 16 h while the temperature was slowly raised to RT. Thereaction mixture was quenched with 4 N HCI (400 mL) and the aqueous part was separated andextracted with EtOAc (3x 100 mL). The combined organic layers were washed with brine and dried overNa2504. The solvents were evaporated and the residue was triturated with EtOAchexane (1:4, 200 mL),filtered and washed with EtOAc/hexane (1:4, 100 mL). Brown solid. Yield: 26.0 g (92%). HPLC (method 1): R = 2.92 mi mlz [M+H] = 240.0 (MW calc. 238.08)

The chemical industry reduces the impact on the environment during synthesis 6-Bromoindolin-2-one. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GRUeNENTHAL GMBH; KONETZKI, Ingo; JAKOB, Florian; WAGENER, Markus; WELBERS, Andre; HESSLINGER, Christian; (138 pag.)WO2017/108203; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem