Tag: M.W=200-300

Synthetic Route of 552330-86-6,Some common heterocyclic compound, 552330-86-6, name is 5-Bromoisoindolin-1-one, molecular formula is C8H6BrNO, 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.

Intermediate No.165 *romo-2 -trimethyl-2 -dihvdro-l/y soindol-l-one5-Bromo-2,3-dihydro-lH-isoindol-l-one (150 mg, 0.71 mmol) was dissolved in DMF (3.5 mL) and stirred at ambient temperature. NaH (85 mg, 2.1 mmol, 60% dispersion in oil) was carefully added in two portions, and the resulting mixture was allowed to stir for 15 minutes before Mel (151 mg, 1.06 mmol) was added. The mixture was allowed to stir at ambient temperature for 30 minutes before water (10 mL) was carefully added. The mixture was extracted with EtOAc, and the organic layer was washed with water, brine, dried over anhydrous MgS04, filtered, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-20% EtOAc/hexanes). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound.LRMS (ESI) calc’d for Ci iH12BrNO [M+H]+: 254, Found: 254.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromoisoindolin-1-one, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; BRUBAKER, Jason; DINSMORE, Christopher J.; HOFFMAN, Dawn Marie; JUNG, Joon; LIU, Duan; PETERSON, Scott; SIU, Tony; TORRES, Luis E.; ZHANG, Hongjun; WEI, Zhongyong; SHI, Feng; WO2013/40863; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1029691-06-2, name is 2-(3-Oxocyclopentyl)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. Safety of 2-(3-Oxocyclopentyl)isoindoline-1,3-dione

Mix (+/-)-2-(3-oxo-cyclopentyl)-isoindole-1,3-dione (12.7 g, 55.3 mmol) and 4-cyanophenylhydrazine-HCl (8.53 g, 50.3 mmol) in HOAc (200 mL) and 4N HCl dioxane (50 mL). Using mechanical stirring, heat the reaction to 90 C. for 18 h, then add additional 4N HCl dioxane (20 mL). Heat the reaction to 100 C. for 18 h. Dilute the reaction mixture with water (600 mL) and collect a black solid by vacuum filtration. Sonicate the solid with MeOH (200 mL), then collect and dry in a vacuum oven to give 10.94 g (66%) of a gray-brown solid. MS (m/z): 328 (M+1), 326 (M-1).

The synthetic route of 1029691-06-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Gavardinas, Konstantinos; Green, Jonathan Edward; Jadhav, Prabhakar Kondaji; Matthews, Donald Paul; US2010/69404; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 20870-90-0, name is 5-Bromo-1-methyl-2-oxoindoline, molecular formula is C9H8BrNO, 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. Quality Control of 5-Bromo-1-methyl-2-oxoindoline

EXAMPLE 59A benzyl 1-methyl-oxindole-5-carboxylate A solution of 5-bromo-1-methyl oxindole (3.75 g, 16.6 mmol) and triethylamine (3.48 mL) in THF (40 mL) was treated with benzyl alcohol (2.58 mL) and PdCl2(dppf) (300 mg), stirred under carbon monoxide (680 psi) at 130 C. for 16 hours, depressurized, filtered through diatomaceous earth (Celite), and concentrated. The concentrate was purified on silica gel with 30% ethyl acetate/hexanes to provide 2.36 g of the desired product. MS (ESI(+)) m/z 299 (M+NH4)+; 1H NMR (CDCl3) delta 8.10-8.07 (m, 1H), 7.95 (s, 1H), 7.47-7.33 (m, 5H), 6.86 (d, J=8.1 Hz, 2H), 5.35 (s, 2H), 3.56 (s, 2H), 3.25 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 20870-90-0, its application will become more common.

Reference:
Patent; Abbott Laboratories; US6228868; (2001); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 1677-48-1, name is 5,6-Dichloroindoline-2,3-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 1677-48-1, Application In Synthesis of 5,6-Dichloroindoline-2,3-dione

Example 2 5,6-dichloro-1-methylisatin (2a). To a solution of 5,6-dichloroisatin (0,15 g; 0.7 mmol) in anhydrous DMF (5 ml) was added sodium hydride (40 mg, 60% dispersion in mineral oil). When the evolution of hydrogen had ceased iodomethane (0.1 ml) was added and the mixture was stirred for 20 min. at ambient temperature. Water (15 ml) and glacial acetic acid (0.1 ml) were added and the product was filtered off, washed with water and dried to yield 5,6-dichloro-1-methylisatin (0.13 g, 81%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5,6-Dichloroindoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; Jensen, Bo Skaaning; Jorgensen, Tino Dyhring; Ahring, Philip K.; Christophersen, Palle; Strobaek, Dorte; Teuber, Lene; Olesen, Soren Peter; US2002/16354; (2002); 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

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

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 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

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. 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, A new synthetic method of this compound is introduced below., Computed Properties of C13H16BrNO2

5-Bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 mL) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 8O0C for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45g, 46%). 1H NMR (MeOH-d4) 7.15 (1 H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H, m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H, s). MS: [M+H]+ 318.

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; ASTEX THERAPEUTICS LIMITED; WO2008/44029; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 118289-55-7, 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. 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 1; 5- (2- (4- (1, 2-benzisotliiazol-3-yl)-l-piperazitiyl) ethyl)-6-chloro-1, 3-diliydro-2H-indole-2-one (Ziprasidone); In a 10 liter three-necked round bottom flask sodium carbonate (742 g) and pure water (3.06 liter) is charged. To the above stirred solution 1, 2-benzisothiazole-3-piperazinyl HCl (611 g, 2 moles) is added at ambient temperature and stirred the reaction mixture additionally for 1 hour. To the obtained suspension 2-Chloroethyl-6-chloro oxindole (430 g, 2 moles) and sodium iodide (20 g) is added. The combined reaction mixture is heated at 60 to 90 C for 20 to 30 hours. After completion of the reaction, reaction mass is cooled to ambient temperature and the slurry thus obtained is stirred for 1 hour more and then filtered. The wet tan colored crude free base is suspended in water (7.50 liter), heated to 75 to 80 C under stirring for 1 hour and filtered at 45 to 50 C temperature. Wet compound is dried at 65 to 70 C for 10 to 12 hours to get desired product in 752 gm yield (HPLC Purity 95 to 96%).

The synthetic route of 6-Chloro-5-(2-chloroethyl)indolin-2-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; WOCKHARDT LIMITED; JAWEED MUKARRAM, Siddiqui, Mohammed; MERWADE, Aravind, Yekanathsa; SINGH, Kumar, Kamlesh, Laxmi; SOLANKI, Pawan, Vrajlal; WO2005/54235; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem