Author: Jessica.F

Application of 17564-64-6,Some common heterocyclic compound, 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-dione, molecular formula is C9H6ClNO2, 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 solution of ammonium O,O-(2-methylpentane-2,4-diyl) dithiophosphate (1) (0.01 mol) was dissolved in absolute methanol (20 mL) and treated with N-(chloromethyl)phthalimide (0.01 mol). The mixture was reuxed for 1 h, fltered and concentrated by distillation under reduced pressure.The resulting concentrated solution crystallized at room temperature. The white solid was fltered, washed with diethylether and dried over P2O5. It was recrystallized with aMeOH:CHCl3 (9:1) mixture.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(Chloromethyl)isoindoline-1,3-dione, its application will become more common.

Reference:
Article; Rastogi, Rupali; Gupta, Srasti; Tarannum, Nazia; Agarwal, Ranu; Butcher; Phosphorus, Sulfur and Silicon and the Related Elements; vol. 192; 3; (2017); p. 300 – 306;,
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. 3484-35-3, name is 5-Methylindolin-2-one, A new synthetic method of this compound is introduced below., Safety of 5-Methylindolin-2-one

General procedure: Equimolar quantity of 5-substituted-1H-indolin-2-ones and 2-(4-formylphenoxy)-N-substituted-phenyl-acetamide was taken into round bottom flask containing 50 mL of methanol, followed by 2-3 drops of piperidine. The reaction mixture was refluxed for 1-4 h or till the end of reaction as confirmed by TLC. Then, it was cooled to room temperature and, the solution was filtered. The obtained residue was recrystallized by using dimethylformamide and ethanol.

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:
Article; Bhadauria, Vivek Singh; Sravanthi, Vishnu; Kumar, Sujeet; Das, Debajyoti; De Clercq, Erik; Schols, Dominique; Tokuda, Harukuni; Karki, Subhas S.; Acta poloniae pharmaceutica; vol. 74; 1; (2017); p. 137 – 145;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 105310-75-6, A common heterocyclic compound, 105310-75-6, name is cis-2-((1,3-Dioxoisoindolin-2-yl)methyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide, molecular formula is C23H24N2O3, 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.

40% methyl amine solution (prepared by mixing methyl amine (210 g) with water (190 ml)) was added to (Z)-l -phenyl- l-diethylaminocarbonyl-2- phthalimidomethylcyclo propane compound of formula-6 (100 g) obtained from example-3 in toluene (450 ml) at 20-30C and stirred for 24 hours. After completion of the reaction both the organic and aqueous layers were separated; the aqueous layer was extracted with toluene. Both the organic layers were combined and washed with water. Carbon (8 g) was added to the organic layer, heated to 50-55C and stirred for 45 minutes. Filtered the reaction mixture and washed with toluene. Distilled off the solvent from filtrate under reduced pressure to get the title compound.Yield: 65 grams

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; MSN LABORATORIES LIMITED; THIRUMALAI RAJAN, Srinivasan; ESWARAIAH, Sajja; SATYANARAYANA, Revu; WO2012/46247; (2012); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 1074-82-4,Some common heterocyclic compound, 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, molecular formula is C8H4KNO2, 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.

(0331) A mixture of potassium phthalimide (100.0 g, 539.9 mmol, 1.0 equiv.), potassium carbonate (11.2 g, 81.0 mmol, 0.15 equiv.) and N,N-dimethylformamide (DMF) (200 mL) is treated with chloroacetone (47.3 mL, 54.9 g, 593.9 mmol, 1.1 equiv.) at a rate to control the internal temperature at not more than 40 C. After the addition is complete, the reaction mixture is stirred for about 12 hours at about 20-25 C. Water (333 mL) is charged to the reaction mixture at a rate to control the internal temperature at not more than 30 C. The mixture is stirred at about 20-25 C. for about 1 hour, and then the mixture is filtered. The filter cake is washed with water (200 mL), and the product is dried at about 70-80 C. under vacuum with a nitrogen flow for about 12 hours. The product phthalimidoacetone (VII-j) is obtained as a white solid (90.2 g, 97.3 wt. % purity, 80% yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Potassium 1,3-dioxoisoindolin-2-ide, its application will become more common.

Reference:
Patent; Boehringer Ingelheim International GmbH; DANG, Mai Thi Quynh; HAMPEL, Thomas Armin; KOCH, Sandra; NORDSTROM, Fredrik Lars; REEVES, Jonathan Timothy; REICHEL, Carsten; SCHOERER, Marvin; STANGE, Christian; VOLCHKOV, Ivan N.; Zhong, Li; ZIMMERMANN, Uwe Johannes; (38 pag.)US2018/251427; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 35197-64-9, 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. 35197-64-9, name is 2-Bromo-4-(1,3-dioxoisoindolin-2-yl)butanoic acid belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: In this work, previously reported N-benzyl-2-bromo-4-(1,3-dioxoisoindolin-2-yl)butanamide derivatives (25a-e) [44] were obtained by activating the carboxylic acid group of 24 (1 eqv) by using n-propanephosphonic acid anhydride (T3P, 50% in EtOAc, 1 eqv). The reaction was carried out under argon atmosphere for 2hat 0C in dry methylene chloride. Then, distilled triethylamine (1.2 eqv) and the appropriate N-benzylamine (1.1 eqv) were added to the reaction mixture [57]. The reaction was continued at room temperature for 12h. The products were purified by column chromatography over silica gel (DCM/acetone=9:1) to yield 25a-e as a white solid.

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, 2-Bromo-4-(1,3-dioxoisoindolin-2-yl)butanoic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Article; ?mudzki, Pawe?; Fija?kowski, ?ukasz; Furga?a, Anna; Gryz?o, Beata; Hoefner, Georg C.; Kulig, Katarzyna; Malawska, Barbara; Malawska, Katarzyna; Nowaczyk, Alicja; Podkowa, Adrian; Rapacz, Anna; Sa?at, Kinga; Wanner, Klaus T.; Zar?ba, Paula; European Journal of Medicinal Chemistry; vol. 188; (2020);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 5332-26-3,Some common heterocyclic compound, 5332-26-3, name is 2-(Bromomethyl)isoindoline-1,3-dione, molecular formula is C9H6BrNO2, 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.

1.02 g (4.2 mmol) of N-(bromomethyl)phthalimide (1c), 1.09 g (8.0 mmol) of phenylacetic acid and 0.56 g (4.0 mmol) of potassium carbonate were mixed in 120 mL of a mixture of acetone and distilled water (1:1 vol %). The solution was heated for 5 h to approx. 70 C. After evaporation of acetone, the product precipitated as a colorless solid. Filtration, washing with water and drying gave 465 mg (1.6 mmol; 37%) of 6 as a colorless solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(Bromomethyl)isoindoline-1,3-dione, its application will become more common.

Reference:
Article; Anamimoghadam, Ommid; Mumtaz, Saira; Nietsch, Anke; Saya, Gaetano; Motti, Cherie A.; Wang, Jun; Junk, Peter C.; Qureshi, Ashfaq Mahmood; Oelgemoeller, Michael; Beilstein Journal of Organic Chemistry; vol. 13; (2017); p. 2833 – 2841;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 18711-13-2,Some common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, molecular formula is C8H3Cl2NO2, 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 1- Synthesis of 4,7 dichloroisatin analogs [0143] An appropriate acetophenone and 4, 7-dichloroisatin were condensed in the presence of a catalytic amount of diethylamine to prepare the desired compound in quantitative yield. Example compounds: R1 = 4′-CN (PT-1-11); 2′-OCH3 (PT-1-12) ; 3*-OCH3 (PT-1-18) ; 2′,4′-OCH3 (PT-1-19); 2′,3*-OCH3 (PT-1-20); 3*,4OCH3 (PT-1-21); 3*,5*OCH3 (PT-1-22); 2′,3*,4′,-OCH3 (PT-1-23); 3*,4′,5*-OCH3 (PT-1-13); 4′-OC2H5 (PT-1-14); 4′-CF3 (PT-1-15); 4′- OCF3 (PT-1-16); 4′-N(CH3)2 (PT-1-17); 4′-OPh (PT-1-60); 4′-SCH3 (PT-1-67); and 4′-C(CH3)2 (PT-1-67).

The synthetic route of 18711-13-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GEORGETOWN UNIVERSITY; TORETSKY, Jeffrey, A.; BROWN, Milton, Lang; TOSSO, Perrer, N.; UREN, Aykut; KONG, Yali; WO2013/155341; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 41910-64-9, 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 41910-64-9 as follows.

(1) Penta-O-acetyl-5-thio-D-glucopyranose (1323 mg) was suspended in ethyl alcohol (30 ml), and thereto was added sodium methoxide (28% methanol solution, 2 drops). The mixture was stirred at room temperature for one hour under argon atmosphere to give a solution of 5-thio-D-glucopyranose. To the solution were added 4-chloroindoline (500 mg) and ammonium chloride (174 mg), and the resultant mixture was refluxed for 22 hours. After being cooled to room temperature, the solvent was evaporated under reduced pressure to give crude 4-chloro-1-(5-thio-beta-D-glucopyranosyl)indoline, which was used in the subsequent step without further purification.

According to the analysis of related databases, 41910-64-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Tanabe Seiyaku Co., Ltd.; US2008/27014; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 18711-13-2, These common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-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.

3-(2-(4-(Aziridin-l-yl)phenyl)-2-oxoethyl)-4,7-dichloro-3-hydroxyindolin-2-one (EXAMPLE 2): To 4,7-dichloroindoline-2,3-dione (A) (300 mg, 1.39 mmol) in 15 mL of methanol were l-(4-(aziridin-l-yl)phenyl)ethanone (B) (0.9 g, 5.5 mmol) and 10 drops of diethylamine (2). The reaction was stirred at 50C for 24 hours. The solvent was removed and the residue was purified with flash chromatography (0-5% Methanol/CH2C12) to get an off white solid. 3-(2-(4-(Aziridin-l-yl)phenyl)-2-oxoethyl)-4,7-dichloro-3-hydroxyindolin-2-one (EXAMPLE 2): off-white solid; 1H NMR (DMSO-d6, 400 MHz) delta 2.16 (s, 4H), 3.64 (d, 1H, J=16 Hz), 4.32 (d, 1H, J=16Hz), 6.41(s, 1H), 6.89(d, 1H, J=8Hz), 7.05 (d, 2H, J=8Hz), 7.30 (d, 1H, J=8Hz), 7.80 (d, 2H, J=8Hz), 10.95 (s, 1H).

Statistics shows that 4,7-Dichloroindoline-2,3-dione is playing an increasingly important role. we look forward to future research findings about 18711-13-2.

Reference:
Patent; TOKALAS, INC.; VERNIER, Jean-michael; (82 pag.)WO2016/57698; (2016); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-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. Quality Control of 6-Chloro-5-(2-chloroethyl)indolin-2-one

i. Synthesis of 5- [2- [4- (1, 2- benzisothiazol-3-yl) -1-piperazinyl] ethyl] -6-chloro-1, 3-dihydro-2H-indol-2-one (Ziprasidone base) An amount of 5.00 g (0.023 mol) of 3-(1-piperazinyl)1,2-benzisothiazole, 5.77 g (0.025 mol) of 6-Chloro-5-(2-Chloroethyl)-1,3-Dihydro-2H-Indol-2-One, 2.44 g (0.023 mol) of Na2CO3 and 37.5 ml of 1-ethyl-3-methylimidazolium ethylsulfate were mixed to obtain homogenous suspension. The suspension was heated to about 100 C and maintained at the same temperature until the end of reaction. The reaction mixture was then cooled to room temperature and precipitated with 50 ml of MeOH, mixed for 1 hour and filtrated. Finally, 10 g of product containing 97.6 area % (by HPLC) of Ziprasidone base were obtained. ii. Synthesis of 5- [2- [4- (1, 2- benzisothiazol-3-yl) -1-piperazinyl] ethyl] -6-chloro-1, 3-dihydro-2H-indol-2-one (Ziprasidone base) Example 13.i. was repeated with the exception that 50 ml of 2-propanol were used instead of methanol for precipitation. 10.1 g of wet product containing 97.6 area % (by HPLC) of Ziprasidone base was obtained.; iii. Synthesis of 5- [2- [4- (1, 2- benzisothiazol-3-yl) -1-piperazinyll ethyl] -6-chloro-1, 3-dihydro-2H-indol-2-one (Ziprasidone base) Filtrate (mixture of ionic liquid and methanol) as obtained according to Example 13.i. was reused for reaction in such way that methanol was evaporated. Example 13.i. was repeated with the exception that reused 1-ethyl-3-methylimidazolium ethylsulfate was added. Purity of the obtained product was > 90 area % (by HPLC).

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

Reference:
Patent; KRKA; EP1889844; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem