Category: indolines-derivatives

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

Reference of 825-70-7, These common heterocyclic compound, 825-70-7, name is 5-Fluoro-2-methylindoline, 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 15c and Example 16c Synthesis of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one and of (-)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one 430 mg of 5-fluoro-2-methyl-2,3-dihydro-1H-indole (reference example 4c) and 872 mg of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride are added to a solution of 1.1 g of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate in 25 ml of N,N-dimethylformamide and 25 ml of pyridine. The reaction mixture is stirred at ambient temperature for 48 hours and then 100 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with a 0.1N hydrochloric acid solution, water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol (95/05: v/v), so as to give 538 mg of 2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one.The enantiomers are separated by chiral chromatography on a Whelk 01 SS, 10 mum column (10 mum, 80¡Á350 mm), elution being carried out with a mixture of: heptane/dichloromethane/ethanol/methanol: 60/20/10/10; flow rate: 240 ml/min.212 mg of (+)-2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained, as first enantiomer, in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.28 (d, J=6.6 Hz, 3H); 2.70 (d, J=16.2 Hz, 1H); 3.33 (s, 3H); 3.36 to 3.44 (m, 5H); 3.58 (m, 4H); 4.02 (d, J=16.6 Hz, 1H); 4.27 (d, J=16.6 Hz, 1H); 4.73 (m, 1H); 5.36 (s, 1H); 7.00 (td, J=2.9 and 8.9 Hz, 1H); 7.16 (dd, J=2.9 and 8.9 Hz, 1H); 7.94 (dd, J=5.0 and 8.9 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.76;[M+H]+: m/z 387; [M-H]-: m/z 385;Optical rotation: alphaD=+72.0 (c=1.704 mg/0.5 ml CH3OH)Then the second enantiomer (Tr=17.61 min), 210 mg of (-)-2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one, is obtained in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.28 (d, J=6.4 Hz, 3H); 2.70 (d, J=16.2 Hz, 1H); 3.33 (s, 3H); 3.37 to 3.44 (m, 5H); 3.59 (m, 4H); 4.02 (d, J=16.6 Hz, 1H); 4.27 (d, J=16.6 Hz, 1H); 4.72 (m, 1H); 5.36 (s, 1H); 7.00 (td, J=3.0 and 8.8 Hz, 1H); 7.16 (dd, J=3.0 and 8.8 Hz, 1H); 7.93 (dd, J=5.1 and 8.8 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.76;[M+H]+: m/z 387; [M-H]-: m/z 385;Optical rotation: alphaD=-59.5 (c=2.182 mg/0.5 ml CH3OH)

The synthetic route of 825-70-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SANOFI; Brollo, Maurice; Carry, Jean-Christophe; Certal, Victor; Didier, Eric; Doerflinger, Gilles; EL Ahmad, Youssef; Filoche-Romme, Bruno; Halley, Frank; Karlsson, Karl Andreas; Schio, Laurent; Thompson, Fabienne; US2013/274253; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 32692-19-6, name is 5-Nitroindoline, 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. Safety of 5-Nitroindoline

Manufacturing Example 1 tert-Butyl 5-nitro-1-indolinecarboxylate To a solution of 500mg (3.05mmol) of 5-nitroindoline in 10mL of anhydrous dichloromethane was added 798mg (3.65mmol) of di-tert-butyl dicarbonate under ice cooling, and the mixture was stirred for 1.5 hours. Then, to this mixture was added catalytic amount of 4-dimethylamiopyridine and the mixture was stirred for 1 hour at room temperature. Water was added to the reaction mixture and the mixture was extracted with dichloromethane. The organic layer was washed with saturated saline solution and dried over with anhydrous sodium sulfate. The solvent was removed under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 6/1) to give 800mg (99%) of the title compound.

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

Reference:
Patent; Daiichi Asubio Pharma Co., Ltd.; EP1775298; (2007); A1;,
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

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

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

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