Author: Jessica.F

Electric Literature of 667463-64-1, 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. 667463-64-1 name is 6-Bromo-1-methylindoline-2,3-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.

Step 2: Synthesis of Intermediate 1-12.2 1-12.1 (15.0 g, 63 mmol) and hydrazine hydrate (30 mL, 618 mmol) are heated to 125 C for 72 h. To the cool reaction mixture DCM is added and extracted with water and 1 M HC1. The organic layer is dried over MgSC>4 and concentrated. The crystallized residue is dissolved in DCM, methanol is added and the DCM is removed in vacuo. The crystallized product is filtered by sunction and washed with cold methanol. Yield 63%, m/z 226/228 [M+H]+, rt 1.16 min, LC-MS Method V001 003.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromo-1-methylindoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRAUERT, Matthias; GRUNDL, Marc; HAEBEL, Peter, Wilhelm; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; BINDER, Florian; VINTONYAK, Viktor; WO2014/140075; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. Computed Properties of 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.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5332-26-3, its application will become more common.

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);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 897957-06-1,Some common heterocyclic compound, 897957-06-1, name is 6-Bromo-1-methylindolin-2-one, 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.

Step 3: Synthesis of Intermediate R12To 1-5.2 (32.0 g, 142 mmol) in anhydrous dioxane (400 mL) is added Ri 1 (54.4 g, 241 mmol) andpotassium acetate (41.6 g, 424 mmol). The mixture is purged with Argon, [1, 1?-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) as a complex with dichloromethane (11.2 g, 14 mmol) is added and the mixture is heated to 90 C for 2 h. The reaction mixture is diluted with ethyl acetate and water, the organic layer is washed with water, dried over Mg504 and concentrated. The residue is purified via flash chromatography (cyclohexane / EA = 70:30). Yield72%, m/z 274 [M+H]+, rt 0.67 mi LC-MS Method VOil SOl.

The synthetic route of 897957-06-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRAUERT, Matthias; GRUNDL, Marc; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; WO2014/140091; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-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. SDS of cas: 3891-07-4

To a solution of 4a (1.88 g, 20 mmol), N-(2-hydroxyethyl)phthalimide (3.82 g, 20 mmol) and triphenylphosphine (7.87 g, 30 mmol) in tetrahydrofuran (30 mL) was added dropwise a solution of diethyl azodicarboxylate (4.7 mL, 30 mmol) in tetrahydrofuran (10 mL) at 0C over 0.5 h. The mixture was stirred at the same temperature for 6h and concentrated under reduced pressure. The residue was diluted in diethyl ether and stirred at -5 to 0C for 30 min and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel), eluting with petroleum ether and ethyl acetate (6:1, v/v) to give 5a (5.02g, 94 %) as a off-white solid.

The synthetic route of 2-(2-Hydroxyethyl)isoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wang, Minghua; Ye, Cheng; Liu, Mingliang; Wu, Zhaoyang; Li, Linhu; Wang, Chunlan; Liu, Xiujun; Guo, Huiyuan; Bioorganic and Medicinal Chemistry Letters; vol. 25; 14; (2015); p. 2782 – 2787;,
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., category: indolines-derivatives

A solution of N-(4-oxocyclohexyl)phthalimide (14, 3.53 g, 15 mmol, 1 eq.) and 4-(methylsulfonyl)phenylhydrazine (2.70 g, 15 mmol, 1 eq.) in glacial acetic acid (110 mL) was heated at reflux for 47 h. The mixture was concentrated in vacuo and the residue was dissolved in CH2Cl2 (200 mL). Afterwards, the organic layer was washed with water (2 * 70 mL) and brine (70 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by fc with a gradient (? = 6 cm, l = 13 cm, v = 60 mL, cyclohexane/CH2Cl2 60:40, 50:50, 30:70, 0:100, CH2Cl2/methanol 100:10, Rf = 0.51 (cyclohexane/ethyl acetate/formic acid 3:7:0.2)). Pale yellow solid, mp 282-284 C, yield 4.50 g (79%). Purity (HPLC): 86.6% (tR = 19.6 min). C21H18N2O4S (394.5 g/mol). Exact mass (APCI): m/z = 395.1072 (calcd. 395.1060 for C21H19N2O4S [M + H+]). 1H NMR (600 MHz, DMSO-D6): delta (ppm) = 2.11 (d, J = 12.3 Hz, 1H, 2-H), 2.64-2.74 (m, 1H, 2-H), 2.92-3.01 (m, 3H, 1-CH2, 4-H), 3.12 (s, 3H, CH3), 3.29-3.33 (m, 1H, 4-H), 4.47-4.54 (m, 1H, 3-H), 7.49 (d, J = 8.6 Hz, 1H, 8-H), 7.56 (dd, J = 8.6/1.4 Hz, 1H, 7-H), 7.84-7.93 (m, 5H, 5-H, 4-Hphth, 5-Hphth, 6-Hphth, 7-Hphth), 11.45 (s, 1H, NH). 13C NMR (151 MHz, DMSO-D6): delta (ppm) = 22.5 (1C, C-1), 24.2 (1C, C-4), 26.2 (1C, C-2), 44.6 (1C, CH3), 47.4 (1C, C-3), 108.3 (1C, C-4a), 111.2 (1C, C-8), 117.3 (1C, C-5), 118.9 (1C, C-7), 123.0 (2C, C-4phth, C-7phth), 126.3 (1C, C-4b), 130.7 (1C, C-6), 131.5 (2C, C-3aphth, C-7aphth), 134.5 (2C, C-5phth, C-6phth), 136.8 (1C, C-9a), 138.5 (1C, C-8a), 167.9 (2C, C=O). FTIR (neat): ? (cm-1) = 3348 (m, N-H), 2939 (w, C-H, aliph), 1697 (s, C=O), 1620 (w, C-C, arom), 1130 (s, SO2).

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 104618-32-8.

Reference:
Article; Heimann, Dominik; Boergel, Frederik; de Vries, Henk; Bachmann, Kim; Rose, Victoria E.; Frehland, Bastian; Schepmann, Dirk; Heitman, Laura H.; Wuensch, Bernhard; European Journal of Medicinal Chemistry; vol. 143; (2018); p. 1436 – 1447;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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 141452-01-9 as follows. HPLC of Formula: C10H11NO2

1.26 g (5.8 mmoles) of di-tert-butyldicarbonate and 0.80 ml (5.8 mmoles) of Et3N are added successively at 20 C. to a solution of 0.85 g (4.8 mmoles) of methyl 5-indolinecarboxylate (J Heterocycl Chem (1993) 30 (4), 1133-1136) in 15 ml of CH2Cl2. The reaction mixture is stirred for 20 hours and concentrated to dryness under vacuum. The residue is divided between 50 ml of AcOEt and 25 ml of water. After stirring and decanting, the organic phase is washed with 25 ml of salt water, dried over MgSO4, filtered and concentrated to dryness under vacuum. The powder obtained is suspended in heptane, stirred and filtered in order to produce a white solid with a yield of 73%. Melting point=107-107.5 C.

According to the analysis of related databases, 141452-01-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Societe de Conseils de Recherches et d’Applications Scientifiques (S.C.R.A.S.); US6747024; (2004); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 1035235-27-8, These common heterocyclic compound, 1035235-27-8, name is tert-Butyl 4-bromoisoindoline-2-carboxylate, 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. A suspension of 3-amino-N-methylisoquinoline-6-carboxamide TFA salt (Intermediate 6, 0.40 g, 1.262 mmol), tert-butyl 4-bromoisoindoline-2-carboxylate (Intermediate 1, 0.15 g, 0.505 mmol), and potassium tert-butoxide (0.28 g, 2.525 mmol) in toluene (10 ml) was degassed with nitrogen for 10 min at rt. BetaIotaNuAlphaRho (0.047 g, 0.050 mmol) and Pd2(dba)3 (0.032 g, 0.050 mmol) were added to the reaction mixture at rt. The reaction mixture was heated at 105C for 2 h. The resulting reaction mixture was cooled to rt, poured into water (20 ml) and extracted with EtOAc (2 x 40 ml). The combined organic phase was dried over Na2S04, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (4% MeOH in DCM) yielding tert-butyl 4-((6-(methylcarbamoyl)isoquinolin-3-yl)amino)isoindoline-2-carboxylate (0.135 g, 0.322 mmol). LCMS: Method A, 2.278 min, MS: ES+ 419.5.

The synthetic route of 1035235-27-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MISSION THERAPEUTICS LIMITED; GIBSON, Karl Richard; JONES, Alison; KEMP, Mark Ian; MADIN, Andrew; STOCKLEY, Martin Lee; WHITLOCK, Gavin Alistair; WOODROW, Michael D; (241 pag.)WO2017/158388; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 64483-69-8, name is 5-Acetylindolin-2-one, 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 64483-69-8, Application In Synthesis of 5-Acetylindolin-2-one

5-Ethyl-2-oxindole To 5-Acetyl-2-oxindole (2 g) in 15 mL of trifluoroacetic acid in an ice bath was slowly added 1.8 g of triethylsilane; the reaction was then stirred at room temperature for 5 hours. One mL of triethylsilane was added and the stirring continued overnight. The reaction mixture was poured into ice water and the resulting precipitate collected by vacuum filtration, washed copiously with water and dried under vacuum to give 1.3 g (71% yield) of the title compound as a yellow 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, 5-Acetylindolin-2-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SUGEN, Inc.; US2003/69421; (2003); A1;; ; Patent; Sugen, Inc.; US6051593; (2000); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 13220-46-7, These common heterocyclic compound, 13220-46-7, name is 4-Methylindolin-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.

4-Methyl-3-(3-methyl-1H-indol-2-ylmethylene)-1,3-dihydro-indol-2-one A mixture of 4-methyl-2-oxindole (147 mg) (prepared as described in Compound IN-015), 3-methyl-indole-2-carbaldehyde (190 mg) (prepared according to Synthetic Communications, 1986, 16, 1799) and piperidine (10 mg) in ethanol was heated in a sealed tube at 95 C. for 4 hours. The mixture was cooled to room temperature. The solid was collected by vacuum filtration, washed with cold ethanol and dried in vacuum oven for overnight to give 4-methyl-3-(3-methyl-1H-indol-2-ylmethylene)-1,3-dihydro-indol-2-one. 1H NMR (360 MHz, DMSO-d6) delta13.07 (s, br, 1H, NH), 11.0 (s, br, 1H, NH), 7.78 (s, 1H, H-vinyl), 7.64 (d, J=8 Hz, 1H), 7.51 (d, J=8 Hz, 1H), 7.27 (dt, J=1, 8 Hz, 1H), 7.04-7.12 (m, 2H), 6.85 (d, J=8 Hz, 1H), 6.78 (d, J=8 Hz, 1H), 2.64 (s, 3H, CH3), 2.52 (s, 3H, CH3). MS El 288.

Statistics shows that 4-Methylindolin-2-one is playing an increasingly important role. we look forward to future research findings about 13220-46-7.

Reference:
Patent; SUGEN, Inc.; US2002/183364; (2002); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 6341-92-0,Some common heterocyclic compound, 6341-92-0, name is 6-Chloroisatin, molecular formula is C8H4ClNO2, 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 25-mL flask, equipped with a magnetic stirring bar, was charged with 2-(1,3-dithiolan-2- ylidene)acetonitrile 1a (143 mg, 1.0 mmol), isatin 2a (74 mg, 0.5 mmol), and MeCN (3.0 mL), followed by addition of a solution of I2 (25 mg, 0.1 mmol) in MeCN (1.0 mL). The reaction mixture was stirred at 80 C for 12 h. After 1a was consumed, as indicated by TLC, the reaction mixture was quenched with saturated aqueous Na2S2O3 (1.0 mL) and water (20.0 mL), and stirred for another 10 min. The fully precipitated solid was filtered and washed with water (20.0 mL). Then it was further washed with petroleum ether-ethyl acetate (1/1, V/V, 20.0 mL) and dried under vacuum to afford 3a.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Chloroisatin, its application will become more common.

Reference:
Article; Liang, Deqiang; Li, Xiangguang; Yang, Juan; Li, Yanni; Wang, Baoling; Cheng, Ping; Synthetic Communications; vol. 46; 23; (2016); p. 1924 – 1931;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem