Indolines-derivatives

Some common heterocyclic compound, 391-12-8, name is 7-(Trifluoromethyl)isatin, molecular formula is C9H4F3NO2, 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. Recommanded Product: 391-12-8

EXAMPLE 6 20 parts of a 30 percent strength by weight solution of sodium methylate in methanol are added to 21.5 parts of 7-trifluoromethylisatin in 300 parts of methanol at 0° C., resulting in a violet solution. 8 parts of a 50 percent strength by weight hydrogen peroxide solution are then added at 0° C., after which the mixture is stirred for one hour at room temperature. The reddish solution is concentrated, water is added, the pH is brought to 8 with hydrochloric acid and the batch is extracted by shaking with methylene chloride. After concentrating the methylene chloride phase, 16.2 parts (74percent of theory) of methyl 3-trifluoromethylanthranilate are obtained. H1 –NMR (CDCl3): delta=3.8 ppm (s), 6.4 (s, N–H2), 6.6 (t), 7.5 (d) and 7.95 (d).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 391-12-8, its application will become more common.

Reference:
Patent; BASF Aktiengesellschaft; US4310677; (1982); A;,
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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. 7147-90-2, name is 5-Chloroisoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C8H4ClNO2

To a solution of 5-chloro-isoindole-l,3-dione (5.0 g, 27.5 mmol) in DCM (200 mL) was added ethylmagnesium chloride (2 M in THF, 41.3 mL) dropwise at 0 C. After the addition, the mixture was allowed to stir at 0 C for 3 hours before it was quenched with satd. aq. NH4C1 solution. After extraction with DCM, the organic layer was washed with brine, dried over anhy. Na2S04, filtered and concentrated in vacuo to give a crude product containing a mixture of two regioisomers (5.82 g, 100%). MS: 212.0 (M+H+).

According to the analysis of related databases, 7147-90-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; AEBI, Johannes; AMREIN, Kurt; CHEN, Wenming; HORNSPERGER, Benoit; KUHN, Bernd; LIU, Yongfu; MAERKI, Hans P.; MAYWEG, Alexander V.; MOHR, Peter; TAN, Xuefei; WANG, Zhanguo; ZHOU, Mingwei; WO2013/79452; (2013); A1;,
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Related Products of 7699-18-5, These common heterocyclic compound, 7699-18-5, name is 5-Methoxyindolin-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.

General procedure: A suspension of indolinone (0.3mmol), aldehyde (0.3mmol) and pyridine (30muL) in methanol (1mL) were heated under microwave irradiation at 100 C for 30 minutes. The reaction mixture was cooled to room temperature and the resulting precipitate was removed by filtration, carefully washed with methanol and dried in vacuo. When no precipitate was observed methanol was removed under vacuum and the residue was purified by silica gel chromatography to give the desired product.

The synthetic route of 7699-18-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Goering, Stefan; Taymans, Jean-Marc; Baekelandt, Veerle; Schmidt, Boris; Bioorganic and Medicinal Chemistry Letters; vol. 24; 19; (2014); p. 4630 – 4637;,
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Related Products of 6941-75-9, 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. 6941-75-9 name is 5-Bromoisoindoline-1,3-dione, 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.

Heck reaction of 4-Bromophthalic imide with 1,7-Octadien (Heck condition) 1 g 4-Bromophthalic imide (6.167 mmol), a two-fold excess 1,7-Octadien (12.33 mmol) and the catalysator system were solved in 50 ml DMF. The catalysator system consisted of Palladiumacetate (5 mol-% to Imide: 0.31 mmol), 0.92 mmol Triphenylphosphane and 6.17 mmol Triethylamin. The solution has been heated for 24 h at 150 C (Control of reaction progress via thin layer chromatography with CH2Cl2: n-Hexane [5:1]). From the resulting dark brown solution the solvent was removed by reduced pressure. The obtained viscous brown raw product was solved with 80 ml CH2Cl2 and washed three times (3 x 200 ml) with a saturated H2O/NaCl solution. After that the CH2Cl2-phase was dried with MgSO4 and the solvent was removed by reduced pressure. The viscous brown product (1) was dried under constant vacuum.Yield : quant. IR : v 1772, 1717 (s, Imide) cm-1 MS / ESI : 401.14972 m/z (M+H+)

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

Reference:
Patent; DENTSPLY DETREY GmbH; E, Klee, Joachim; Retzmann, Nils; Ritter, Helmut; Szillat, Florian; EP2759289; (2014); A1;,
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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.

Example 8: 6-((R)-5-{[((RS)-2-methoxy-8,9-dihydro-furo[2,3-Lambda]quinolin-9-ylmethyl)- amino] -methyl}-2-oxo-oxazolidin-3-yl)-4H-benzo [ 1 ,4] thiazin-3-one:; 8.i. rac-3-( 1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-yl)-2-(7-fluoro-2-methoxy-quinolin-8-yl)- propionic acid methyl ester:; To a solution of LiEtaMDS (IM in TEtaF, 9.6 niL) was added at -78C a solution of (7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester (2.0 g, 8.0 mmol; prepared as in WO 2007/081597) in TEtaF (16 mL) over lO min. After stirring the resulting orange mixture for 1 h at -78C, a solution of Lambda/-(bromomethyl)phthalimide (1.2 eq.) in TEtaF (16 mL) was added dropwise over 10 min. The mixture was stirred 1 h at -78C and then at it overnight. The yellow solution was quenched with 17V EtaC1 (80 mL) and then extracted with DCM. The combined org layers were washed with water, dried over MgSO4, concentrated and purified by CC (Etaept/EA 1 : 1) to give 1.89 g of a yellow solid which was recrystallized from EA/MeOEta/NEta4OEta (90:10:1) to afford the title intermediate as a colourless solid (924 mg, 28% yield). MS (ESI, m/z): 409.3 [IVB-H+].

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:
Patent; ACTELION PHARMACEUTICALS LTD; HUBSCHWERLEN, Christian; RUEEDI, Georg; SURIVET, Jean-Philippe; ZUMBRUNN ACKLIN, Cornelia; WO2010/15985; (2010); A1;,
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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 5332-26-3 as follows. COA of Formula: C9H6BrNO2

General procedure: S-alkylation of the products was achieved by following a modified method [38]. The oxadiazoles (6a, 6b, 13) (0.02, mol) and K2CO3 (0.022, mol) were stirred in 10mL of acetone for 20 mints followed by the addition of alkyl bromides 7a-c and 7d-m (0.022, mol). The reaction mixture was stirred for 4-6h at room temperature. The reaction mixture was concentrated under vacuum and crude solid gained was recrystallized from methanol to get pure products. 8a: Colorless solid; 55% yield; Rf: 0.55 (chloroform: acetone, 9:1), m.p.; 224-226C; 1H NMR (300MHz, DMSO-d6): delta ppm 10.71 (s, 1H, NH), 7.91-7.84 (m, 4H, Ar-H), 7.64 (dd, 4H, J=18, 9Hz, Ar-H), 7.28 (d, 2H, J=9Hz, Ar-H), 7.06 (d, 2H, J=9Hz, Ar-H), 5.28 (s, 2H, SCH2N), 2.31 (s, 3H, Ar-CH3); 13C NMR (75MHz, DMSO-d6): delta ppm 167.02, 166.74, 160.01, 144.00, 142.03, 140.01, 135.44, 131.76, 129.72, 127.89, 126.94, 124.06, 119.95, 118.11, 43.00, 21.37; IR (cm-1) 3260 (N-H), 3025 (C-H, aromatic), 2948 (C-H, aliphatic), 1716 (C=O), 1602 (C=N), 1308, 1176 (O=S=O); Anal. Calcd for C24H18N4O5S2: C, 56.91; H, 3.58; N, 11.06; O, 15.79; S, 12.66 Found: C, 56.98; H, 3.61; N, 11.11; O, 15.79; S, 12.72.

According to the analysis of related databases, 5332-26-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Batool, Farwa; Hamdani, Syeda Shamila; Hameed, Shahid; Khan, Bilal Ahmad; Mughal, Ehsan Ullah; Saeed, Muhammad; Saleem, Hafiza Nosheen; Bioorganic Chemistry; vol. 96; (2020);,
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Related Products of 603-62-3, 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 603-62-3 as follows.

4-Nitro-lH-isoindole-l, 3(2H)-dione (117.3 g; Formula IV) followed by 1,1- carbonyldiimidazole (138.1 g) were added to a slurry of 3-aminopiperidine-2,6-dione hydrochloride (100 g, Formula III; obtained in Example 1) in acetonitrile (800 mL) to obtain a reaction mixture. The reaction mixture was heated to reflux at 80C to 82C and then stirred for 2 hours. 1,1-Carbonyldiimidazole (19.8 g) was further added to the reaction mixture twice over an interval of one hour. The reaction mixture was cooled to 25 C to 30C and then stirred for 30 minutes. The product obtained was filtered and the wet solid obtained was dried at 50C to 55C under reduced pressure to obtain the title compound. (0076) Yield: 162 g (88%)

According to the analysis of related databases, 603-62-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SUN PHARMACEUTICAL INDUSTRIES LIMITED; BARMAN, Dhiren Chandra; RAM, Sita; RAJBANGSHI, Mantu; NATH, Asok; PRASAD, Mohan; (14 pag.)WO2018/154516; (2018); A1;,
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Related Products of 603-62-3, 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. 603-62-3 name is 3-Nitrophthalimide, 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.

Step 1): An ice cooled solution of bromine (2.5 ml, 48.5 mmol) in 1N KOH aq.solution was added to the solution of 3-nitrophthalimide (9.66 g, 50 mmol) in 1N KOH aq.solution (150 ml) followed by 1N KOH at 0. The mixture was refluxed for 1.5 hours. After cooling, the mixture was neutralized with 2N HCl and stirred at 0 to precipitate 2-amino-6-nitrobenzoic acid, 6.23 g (68%): mp 190 C.

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

Reference:
Patent; Grelan Pharmaceutical Co. Ltd.; Laboratoires Fournier S.C.A.; US5872115; (1999); A;,
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Related Products of 446292-08-6,Some common heterocyclic compound, 446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, molecular formula is C22H19N3O6, 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.

20.0 g (23.80 mmol) of (5)-2-({2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-l,3- oxazolidin-5-yl}methyl)-lH-isoindole-l,3(2H)-dione (compound III, obtained from compound II following the process disclosed in the ‘823 patent) were suspended in 600 mL of acetonitrile and cooled to 0 C. A solution of 3.6 g (7.20 mmol) of sodium sulfide in 60 mL of water was added dropwise to the suspension over 1 hour. The reaction mixture was then stirred for 30 minutes between 5-10 C. The pH was adjusted to 7 using 1.5 M hydrochloric acid solution whilst maintaining the temperature at 5-10 C. The mixture was filtered and 40.0 g of sodium chloride were added to the filtrate. The aqueous phase was collected and kept aside. The organic phase and the solid obtained from the filtration were loaded into the reactor and cooled to 0 C. A solution of 3.6 g (7.20 mmol) of sodium sulfide in 60 mL of water was added dropwise to the suspension over 1 hour. The reaction mixture was then stirred for 30 minutes between 5-10 C. The pH was adjusted to 7 using 1.5 M hydrochloric acid solution whilst maintaining the temperature at 5-10 C. The mixture was filtered and 40.0 g of sodium chloride were added to the filtrate. The aqueous phase was collected and combined with the previous one which was kept aside. The combined aqueous phase was cooled to 0 C. The pH was adjusted to 4-5 using 1.5 M hydrochloric acid solution whilst maintaining the temperature at 5-10 C. 40.0 g of sodium chloride were added and the solution was extracted twice with 600 mL of acetonitrile. The combined organic phases were dried with 60 g of anhydrous sodium sulfate, filtered and concentrated under vacuum without exceeded 38 C . 1 1 .0 g of (5)-2-[({2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-l,3- oxazolidin-5-yl}methyl)carbamoyl]benzoic acid (compound V) were obtained as a pale yellow foam-like solid. Yield: 56.0 %. HPLC chromatographic purity: 95.29% (% area).

The synthetic route of 446292-08-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDICHEM S.A.; MANGION, Bernardino; DURAN LOPEZ, Ernesto; WO2012/35057; (2012); A2;,
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Adding a certain compound to certain chemical reactions, such as: 825-70-7, name is 5-Fluoro-2-methylindoline, 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 825-70-7, Computed Properties of C9H10FN

Example 13c and Example 14c Synthesis of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-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}-6-(morpholin-4-yl)pyrimidin-4(3H)-one 430 mg of 5-fluoro-2-methyl-2,3-dihydro-1H-indole (reference example 4c, step 1c) and 872 mg of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride are added to a solution of 743 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2c of example 1c) 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 580 mg of 2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-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, 80×350 mm), elution being carried out with a mixture of: heptane/dichloromethane/ethanol/methanol: 70/20/5/5; flow rate: 200 ml/min.252 mg of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-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): 1.26 (d, J=6.4 Hz, 3H); 2.70 (m, 1H); 3.34 to 3.48 (m, 5H); 3.60 (m, 4H); 3.71 (d, J=15.9 Hz, 1H); 3.91 (d, J=15.9 Hz, 1H); 4.73 (m, 1H); 5.20 (s, 1H); 7.00 (dt, J=3.0 and 9.1 Hz, 1H); 7.15 (dd, J=3.0 and 9.1 Hz, 1H); 7.95 (dd, J=5.0 and 9.1 Hz, 1H); 11.65 (broad m, 1H)Mass spectrometry: method ARetention time Tr (min)=0.72;[M+H]+: m/z 373; [M-H]-: m/z 371;Optical rotation: alphaD=+60.4 (c=1.939 mg/0.5 ml CH3OH)Then the second enantiomer, 246 mg of (-)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-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): 1.26 (d, J=6.5 Hz, 3H); 2.69 (m, 1H); 3.35 to 3.47 (m, 5H); 3.60 (m, 4H); 3.71 (d, J=15.9 Hz, 1H); 3.91 (d, J=15.9 Hz, 1H); 4.72 (m, 1H); 5.20 (s, 1H); 7.00 (td, J=3.0 and 9.1 Hz, 1H); 7.15 (dd, J=3.0 and 9.1 Hz, 1H); 7.95 (dd, J=5.0 and 9.1 Hz, 1H); 11.66 (broad m, 1H)Mass spectrometry: method ARetention time Tr (min)=0.72;[M+H]+: m/z 373; [M-H]-: m/z 371;Optical rotation: alphaD=-57.9+/-1.1 (c=1.833 mg/0.5 ml CH3OH)

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

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;,
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