Author: Jessica.F

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 1201923-48-9 as follows. Safety of (S)-tert-Butyl (1-(1,3-dioxoisoindolin-2-yl)-3-(3-fluorophenyl)propan-2-yl)carbamate

Step B 2-[(2S)-2-amino-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione [1.0]-hydrogen chloride To a solution of tert-butyl[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]carbamate (9.40 g, 34.9 mmol), triphenylphosphine (9.15 g, 34.9 mmol), and phthalimide (5.14 g, 34.9 mmol) in tetrahydrofuran (100 mL, 1000 mmol) at room temperature was added diethyl azodicarboxylate (17.9 mL, 45.4 mmol). The reaction was stirred at room temperature for 2 hr and then concentrated under reduced pressure. The residue was purified by combi-flash chromatography eluted with EtOAc/hexane (0-40%) to give the desired intermediate. LCMS found: 399.0 (M+1). To the solution of the purified intermediate in methanol (20 mL, 400 mmol) was added 4.0 M hydrogen chloride in dioxane (30 mL, 100 mmol). The mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure to give 3.1 g (26% total yield for the two steps) of the final product, 2-[(2S)-2-amino-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione [1.0]-Hydrogen chloride, as white solid. LC/MS found: 299.0 (M+H)+.

According to the analysis of related databases, 1201923-48-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Incyte Corporation; Huang, Taisheng; Feng, Hao; Kong, Lingquan; Wang, Anlai; Ye, Hai Fen; US2013/96144; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 65435-04-3, A common heterocyclic compound, 65435-04-3, name is 5-(2-Chloroacetyl)indolin-2-one, molecular formula is C10H8ClNO2, 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.

A suspension of 9.3 g of 5-chloroacetyl-2-oxindole was stirred in 90 mL of pyridine at 80-90 C. for 3 hours then cooled to room temperature. The precipitate was collected by vacuum filtration and washed with 20 mL of ethanol. The solid was dissolved in 90 mL of 2.5 N sodium hydroxide and stirred at 70-80 C. for 3 hours. The mixture was cooled to room temperature and acidified to pH 2 with 0.5 N hydrochloric acid. The precipitate was collected by vacuum filtration and washed thoroughly with water to give crude 5-carboxy-2-oxindole as a dark brown solid.

The synthetic route of 65435-04-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUGEN, Inc.; US2002/183364; (2002); A1;,
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 496-12-8 as follows. name: Isoindoline

Example 12; 2-(1,3-Dihydroisoindol-2-yl)-1-(4-dimethylamino-4-phenylcyclohexyl)ethanol; Stage 1; 2-(1,3-Dihydroisoindol-2-yl)-1-(1,4-dioxaspiro[4.5]dec-8-yl)ethanol; A solution of 8-oxiranyl-1,4-dioxaspiro[4.5]decane (1.41 g, 7.66 mmol), isoindoline (1.00 g, 8.43 mmol) and calcium trifluoromethanesulfonate (1.29 g, 3.8 mmol) in anhydrous acetonitrile (60 ml) was stirred at room temperature overnight. The solvent was then concentrated in vacuo. The residue was taken up in ethyl acetate (50 ml) and the solution was washed with 25% potassium carbonate solution (3×50 ml). The aqueous phase was extracted with ethyl acetate (3×40 ml) and the combined organic phases were dried with sodium sulfate and concentrated in vacuo.Yield: 2.04 g (88%), beige-coloured solid1H-NMR (DMSO-d6): 1.24-1.48 (m, 5H); 1.59 (br s, 1H); 1.64-1.74 (m, 3H); 2.56 (dd, 1H, J=7.4, 12.2 Hz); 2.70 (dd, 1H, J=4.7, 12.2 Hz); (m, 2H); 3.44 (m, 1H); 3.83 (s, 4H); 3.83-3.94 (m, 4H); 4.30 (d, 1H, J=4.4 Hz); 7.15-7.26 (m, 4H).

According to the analysis of related databases, 496-12-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GRUeNENTHAL GMBH; US2011/59999; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 200049-46-3,Some common heterocyclic compound, 200049-46-3, name is 7-Bromo-2,3-dihydro-isoindol-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.

7-bromo-2,3-dihydro-lH-isoindol-l-one (5.7 g, 26.88 mmol) was added to sulfuric acid (60 ml) at 0C. The resulting mixture was stirred at 0C for 30 minutes. Then N-iodosuccinimide (9.07 g, 40.32 mmol) was added in one portion and the resulting suspension stirred at 0C for 2 hours. The reaction mixture was poured into ice water, causing a precipitate to form. The precipitate was extracted with ethyl acetate (3 x 200 ml). Both organic and aqueous phases contained precipitates. The organic phase was washed with 10% Na S C (200 ml) to remove excess iodine. The organic layer was dried with sodium sulphate, filtered and evaporated to afford 7-bromo-6-iodo-2,3-dihydro-lH-isoindol-l-one (7.2 g, 79%) as a white solid. 1H NMR (400 MHz, DMSO, 30C) 4.11 (2H, s), 7.43 (1H, d), 7.83 (1H, d), 8.90 (1H, s). m/z: ES+ [M+H]+ = 338.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7-Bromo-2,3-dihydro-isoindol-1-one, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; KETTLE, Jason, Grant; BAGAL, Sharanjeet, Kaur; EATHERTON, Andrew, John; FILLERY, Shaun, Michael; ROBB, Graeme, Richard; LAMONT, Scott, Gibson; KEMMITT, Paul, David; GOLDBERG, Frederick, Woolf; (158 pag.)WO2019/215203; (2019); A1;,
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Indoline | C8H9N – PubChem

Application of 22190-33-6,Some common heterocyclic compound, 22190-33-6, name is 5-Bromoindoline, molecular formula is C8H8BrN, 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.

Procedure A: To a mixture of 5-bromoindoline (10.0 g, 50.8 mmol) in DCM (80 mL), was added a solution of di-tert-butyl dicarbonate (11.2 g, 51.3mmol) in DCM (20 mL). The reaction mixture was stirred at RT for 2 h and concentrated in vacuo to give tert-butyl 5- bromoindoline-1-carboxylate as a yellow oil (18.0 g, quantitative yield). LC-MS (ESI): m/z (M)+ = 297.12 / 299.33

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

Reference:
Patent; REMEDY PLAN, INC.; CRIMMINS, Gregory, Thomas; DE JESUS DIAZ, Dennise, Alexandra; BHURRUTH-ALCOR, Yushma; (483 pag.)WO2019/213570; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 5428-09-1, 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 5428-09-1 as follows.

Example 7-2 Preparation of 2-(4-(trimethylsilyl)but-2-en-1-yl)isoindoline-1,3-dione 12 To a solution of 2-allylisoindoline-1,3-dione 11 (13.0 g, 69.4 mmol) in CH2Cl2 (500 mL) was added AllylTMS (79.0 g, 110 mL, 694 mmol) and Grubbs I generation catalyst. The reaction was heated to 60 °C and stirred under reflux for 4 h. Tris(hydrodxymethyl)phosphine (1 M solution in i-PrOH, 58 mL) was added and stirred under reflux for 12 h, while the color of the reaction turned from black to orange. Sat. aq. NaCl solution (100 mL) was added to the reaction and the organic phase was separated. The aqueous phase was extracted with CH2Cl2 (3 * 200 mL). The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. Column chromatography over SiO2 (Cyclohexane/ EtOAc = 85:15) afforded the title compound (15.0 g, 54.9 mmol, 78.9 percent) as a yellow resin. Rf: 0.57 (Cyclohexane/EtOAc = 85:15) 1H NMR (300 MHz, CDCl3) delta = -0.10 – 0.09 (m, 9H), 1.44 (d, J = 8.2 Hz, 1.6 H), 1.72 (d, J = 8.8 Hz, 0.4 H), 4.21 (d, J = 6.5 Hz, 1.6 H), 4.29 (dd, J = 14.5, 5.9 Hz, 0.4 H), 5.26 – 5.47 (m, 0.8 H), 5.56 – 5.70 (m, 0.2 H), 5.70 – 5.87 (m, 0.8 H), 5.94 – 6.09 (m, 0.2 H), 7.65 – 7.74 (m, 2H), 7.79 – 7.88 (m, 2H). 13C NMR (75 MHz, cdcl3) delta = -2.05, -1.83, -1.43, 18.92, 22.73, 34.72, 39.87, 120.51, 121.30, 123.12, 130.78, 132.24, 133.76, 133.90, 167.99.

According to the analysis of related databases, 5428-09-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V.; The designation of the inventor has not yet been filed; EP2899192; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 104618-32-8, name is 2-(4-Oxocyclohexyl)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. Formula: C14H13NO3

Preparation of 2-amino-6-phthalimido-4,5,6,7-tetrahydrobenzothiazole via 4-(phthalimido)-cyclohexanone; 1.0 Kg of 4-(phthalimido)-cyclohexanol was added in 20.0 L of acetone at 250C to 350C. The reaction mixture was cooled to 50C to 100C and treated with chromic acid solution. 0.2 L of isopropanol was added and stirred for 30 min. The reaction mixture was filtered and washed with acetone (1.0 L). The filtrate was treated with 0.4 kg sodium bicarbonate at 250C to 350C and stirred for 1 h. The reaction mass was again filtered, washed with acetone (1.0 L). Excess of acetone was distilled under vacuum. The residue was treated with 0.5 L ethanol followed by distillation of ethanol under vacuum. The reaction mass was cooled and treated with 3.36 L ethanol at 450C to 250C while gradual cooling. The reaction mixture was further cooled to 150C to 200C and treated with 0.22 L of bromine and 0.43 Kg of thiourea under stirring for 1 h. The reaction mixture was heated to reflux at 750C to 780C for 6 hrs. The reaction mixture was cooled and stirred for 1 hr at 50C to 100C. The product was isolated by centrifuge, washing with ethanol 0.66 L and drying under vacuum at 500C to 550C. (yield: 0.70 Kg).

The synthetic route of 2-(4-Oxocyclohexyl)isoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CADILA HEALTHCARE LIMITED; WO2008/41240; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 169037-23-4, 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. 169037-23-4, name is 5-(Trifluoromethoxy)indoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: A mixture of indoline-2,3-dione 1 (1mmol), l-tryptophan (2a) or l-histidine 2b (1mmol) and (E)-(2-nitrovinyl)benzene 3 (1.1mmol) was heated while stirred in [bmim]Br as the reaction medium (3mL) for 1hat 100C. After completion of the reaction (TLC), EtOAc (5mL) was added and the reaction mixture was stirred for 10min. This treatment was repeated and the combined ethyl acetate layers were removed in vacuo. The crude product was purified by recrystallization of the residue from EtOH (compounds 4) or by column chromatography (compounds 5). After extraction of the product, the ionic liquid was dried under vacuum at 80C for 2h to eliminate any water and could be reused for subsequent runs of the reaction.

The synthetic route of 5-(Trifluoromethoxy)indoline-2,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Article; Arumugam, Natarajan; Almansour, Abdulrahman I.; Kumar, Raju Suresh; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A.; Govindasami, Periyasami; Altaf, Mohammad; Menendez, J. Carlos; Tetrahedron; vol. 74; 38; (2018); p. 5358 – 5366;,
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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. 356068-93-4, name is (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C16H13FN2O3

EXAMPLE 3: Preparation of 7V-(3-(hvdroxycarbamoyl)propyl)5-(TZ)- (5- fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-lH-pyrrole- 3-carboxamide (compound 3) Step 3a. Methyl 4-(5-((Z)-(5-fluoro-2-oxoindolin-3-ylidene)methyl) -2,4- dimethyl- lH-pyrrole-3-carboxamido)butanoate (Compound 110-3) To a stirred solution of compound 1 (0.5 g, 1.67 mmol) in DMF (35 mL) at room temperature was added etaOBt (1.02 g, 7.52 mmol), triethylamine(2.12 mL, 15.03 mmol), ECDI-HCl(1.44 g, 1.52 mmol) and methyl 4-aminobutanate hydrochloride(0.77 g, 5.0 mmol) successively. The mixture was stirred for 24 h at room temperature and then was diluted with water (20 mL), brine (20 mL) and saturated bicarbonate solution (20 mL) and the pH of solution was adjusted to 11-12 with 10 mol/L NaOH. The mixture was filtrated, the solid was collected, washed with water and dried to obtain crude yellow solid product 110-3 (0.32 g, 48.3%). LCMS: m/z 400(M+l), 1H NMR(DMSO-^6) deltal.77 (m, 2H), 2.39 (m, 4H), 2.42 (s, 3H), 2.49 (s, 3H), 3.23 ( t, 2H), 6.85 (m, 2H), 7.60 (t, IH), 7.67 (s, IH), 7.71 (m, IH), 10.89 (s, IH), 13.68 (s, IH).

According to the analysis of related databases, 356068-93-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CURIS, INC.; WO2008/33743; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 1035235-27-8, A common heterocyclic compound, 1035235-27-8, name is tert-Butyl 4-bromoisoindoline-2-carboxylate, molecular formula is C13H16BrNO2, 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. To a stirred solution of tert-butyl 4-bromoisoindoline-2-carboxylate (Intermediate 1, 0.35 g, 1.185 mmol) in 1,4-dioxane: water (4: 1; 20 ml) was added Cs2C03 (0.77 g, 2.371 mmol) at rt under nitrogen. The reaction was purged with nitrogen for 15 min. Pd(PPh3)4 (0.14 g, 0.118 mmol) was added to the reaction mixture and purged with nitrogen for 10 min. 3- (Methoxycarbonyl)phenylboronic acid (CAS Number 99769-19-4; available from Combi Blocks) (0.26 g, 1.422 mmol) was added to the reaction mixture. The reaction mixture was heated at 80C for 24 h. The resulting reaction mixture was cooled to rt, poured into water (20 ml) and extracted with EtOAc (3 x 50). The combined organic phase was washed with brine (80 ml). The organic phase was separated, dried over Na2S04, filtered and concentrated under reduced pressure. The resulting crude material was purified by flash chromatography (5% EtOAc in hexane) yielding tert-butyl 4-(3- (methoxycarbonyl)phenyl)isoindoline-2-carboxylate (0.33 g, 0.932 mmol). LCMS: Method A, 2.782 min, MS: ES+ 298.4 (M-56); 1H NMR (400 MHz, CDC13) delta ppm 8.04 – 8.11 (m, 2 H), 7.62 (d, J=7.2 Hz, 1H), 7.49 – 7.58 (m, 2 H), 7.40 (t, J=7.2 Hz, 1H), 7.31 – 7.33 (m, 1H), 4.69 – 4.79 (m, 4 H), 3.95 (s, 3 H), 1.53 (s, 9 H).

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,
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