Category: indolines-derivatives

Application of 169037-23-4, These common heterocyclic compound, 169037-23-4, name is 5-(Trifluoromethoxy)indoline-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.

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 169037-23-4 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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. Computed Properties of C8H6BrNO

Step 3: 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one 5-Bromo-2,3-dihydro-isoindol-1-one (230 mg, 1.08 mmol), bis(pinacolato)diboron (300 mg, 1.18 mmol), PdCl2dppf (25 mg, 31 mumol) and KOAc (320 mg, 3.26 mmol) are suspended in dioxane (4 ml), purged with nitrogen for 5 minutes and then heated at 85 C. overnight. The solvent is removed in vacuo and the residue partitioned between ethyl acetate and water. The aqueous layer is extracted three times with ethyl acetate and the combined organic phases are washed once with brine, filtered through anhydrous MgSO4 and evaporated. The solid residue is triturated with hexane and dried in vacuo to furnish the title compound (185 mg, 66%) as a grey solid. 1H-NMR (400 MHz, CDCl3) delta (ppm) 1.37 (s, 12H, 4*CH3), 4.45 (s, 2H, CH2), 6.38 (bs, 1H, NH), 7.87 (d, 1H, H), 7.93 (m, 2H, H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 552330-86-6, its application will become more common.

Reference:
Patent; Andrews, Martin James Inglis; Chambers, Mark Stuart; Van De Poel, Herve; Bar, Gregory Louis Joseph; US2009/286798; (2009); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 20876-36-2, name is 5-Aminoindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 5-Aminoindolin-2-one

Preparation of 5-(4-Chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-1,3-dihydro-indol-2-one (4) To a solution of 5-trifluoromethyl-2,4-dichloropyrimidine (214.8 g; 0.921 mol) in 1:1 DCE/tBuOH (1.240 L) was added Zinc chloride 1M solution in ether (1 eq; 0.921 L). After 0.5 hour, 5-amino-oxindole (124 g; 0.837 mol) was added followed by triethylamine (129.4 ml; 0.921 mol) keeping temperature at 25° C. The reaction was allowed to stir at room temperature overnight, then was concentrated and the product triturated from methanol as a yellow solid (224.3 g; 82percent). 1H NMR (DMSO-d6, 400 MHz) .box. 3.29 (s, 2H), 6.76 (d, J=7.9 Hz, 2H), 7.39 (d, J=8.3 Hz), 7.51 (br s, 1H), 8.71 (s, 1H), 10.33 (s, 1H), 10.49 (s, 1H), 13C NMR (DMSO-d6, 100 MHz) .box. 177.0, 161.3, 158.7 (br), 140.7, 132.8, 126.9, 123.7 (q, J=268 Hz), 121.0, 118.7, 111.2 (q, J=32 Hz), 109.6, 36.7; HPLC ret. time: 5.759 min. LRMS (M+) 329.1, 331.1.

The synthetic route of 20876-36-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pfizer Inc; US2005/256145; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 59-48-3, 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. 59-48-3 name is Indolin-2-one, 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.

A stirred mixture of sodium hydride (60%, 31g, 0.79 mol) in dry xylene (500 mL), under a nitrogen atmosphere, was heated to reflux for 30 min. l,3-Dihydro-indol-2-one 16a (100 g, 0.75 mol) was then slowly added via an addition funnel and stirred at reflux for 1.5 hrs. Dimethyl sulfate (104 g, 0.83 mol) was added drop-wise, whereupon the resulting homogeneous solution was refluxed for an additional 2 hrs. After cooling to room temperature, the reaction mixture was washed with water, dried over Na2SC>4, and concentrated under reduced pressure to afford l-methyl-l,3-dihydro-indol-2-one 16b (74 g, 67.3%). .HNMR (300 MHz, CDC13) 5 7.23-7.31 (m, 2 H), 7.04 (t, J= 7.5 Hz, 1 H), 6.82 (d, J= 7.8 Hz, 1 H), 3.52 (s, 2 H), 3.21 (s, 3 H).[0270] A suspension of NaH (60%, 70 g, 0.48 mol) in THF (300 mL) was stirred for 10 min at 0 C. Then a solution of l-methyl-l,3-dihydro-indol-2-one 16b (70 g, 2.88 mol) in THF (200 mL) was added at 0 C, and the mixture was stirred for 1 h at room temperature. Benzyl-bis-(2-chloro-ethyl)-amine (129 g, 0.48 mol) was added in portions at 0 C. The mixture was stirred overnight at room temperature, and then was poured into ice-water, extracted with EtOAc. The combined organic layers were dried over IS^SO^ and concentrated under reduced pressure. The residue was purified by column on silica gel (P.E./E.A. 2:1) to give compound 16c (24 g, 16.3%). lH NMR (300 MHz, CDCI3) 5 7.25-7.42 (m, 7 H), 7.02-7.07 (m, 1 H), 6.83 (d, J= 7.5, 1 H), 3.68 (s, 2 H), 3.19 (s, 3 H), 2.74-2.99 (m, 2 H), 2.66-2.72 (m, 2 H), 1.93-2.01 (m, 2 H), 1.79-1.85 (m, 2 H).[0271] To a solution of compound 16c (12 g, 39.2 mmol) in MeOH (100 mL) was added Pd(OH)2/C (1.5 g, 20%>) under N2. The suspension was hydrogenated under H2 (50 psi) at room temperature for 4.5 hrs. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure to give the deprotected spiroindolone product 16d (8 g, 94.5%). ]H NMR (400 MHz, DMSO-rf6) 5 7.46 (d, J= 7.2,1 H), 7.23-7.27 (m, 1 H), 6.96-7.03 (m, 2 H), 3.04-3.14 (m, 5 H), 2.83-2.89 (m, 2 H), 1.61-1.67 (m, 2 H), 1.45-1.51 (m, 2 H). MS (ESI) m/z 217.1 [M+H]+ [0272] 1.0 eq of deprotected spiroindolone 16d (22 mg, 0.10 mmol) was dissolved in anhydrous l,2-dichloroethane:l,2-dimethoxyethane (1.0 mL, 1:1 v/v) and treated with 1.5 N-Carbethoxy-4-tropinone (30 mg, 0.15 mmol), followed by titanium tetraisopropoxide (88 /xL, 85 mg, 0.30mmol). The vial was flushed with nitrogen and stirred at room temperature ~70 h. The reactionwas then diluted with methanol (1.0 mL), cooled in an ice-BbO bath and treated with sodiumborohydride (8 mg, 0.20 mmol). After warming to room temperature and stirring for 90 min, thereaction was further diluted with methanol (2.0 mL), quenched with 1.0 N NaOH (500 juL) andstirred vigorously at room temperature for 10 min. The suspension obtained was centrifuged(3K rpm, 10 min) and the supernatant concentrated under reduced pressure. The residueobtained was dissolved in MeOH:acetonitrile (1250 fiL, 1:1 v/v), filtered, and purified byreverse-phase HPLC (2-40% CH3CN/0.1% TFA gradient over 10 min) to yield productcompound no. 149. LC/MS (10-99%) m/z [M+H]+398.2, retention time 1.93 min.

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

Reference:
Patent; VERTEX PHARMACEUTICALS, INCORPORATED; WO2006/23852; (2006); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 20870-78-4, name is 5-Bromoindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. name: 5-Bromoindolin-2-one

General procedure: An oven-dried flask was charged with stir bar, oxindole (0.5 mmol), PIDA (0.25 mmol) in dry acetonitrile (4.0 mL). Then to the reaction mixture TEMPO (0.5 mmol) was added in presence of air and the mixture was stirred at room temperature until complete conversion takes place as indicated by TLC analysis. The resulting reaction mixture was extracted with ethyl acetate (3 10 mL). The combined organics were dried with Na2SO4 and dried under vacuum to afford crude solid. Then the crude product was purified by column chromatography on silica gel.

The synthetic route of 20870-78-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Sai Prathima, Parvathaneni; Bikshapathi, Raktani; Rao, Vaidya Jayathirtha; Tetrahedron Letters; vol. 56; 46; (2015); p. 6385 – 6388;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 239463-85-5, A common heterocyclic compound, 239463-85-5, name is (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, molecular formula is C26H31N3O8, 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.

In a 500 ml reaction vessel150 g of purified water and 135 g of ethyl acetate were added and 40.4 g of potassium carbonate was dissolved.To this was added 15 g of 5-[(2R)-2-aminopropyl]-1-[3-(benzyloxy)propyl]2,3-dihydro-1H-indole-7-carbonitrile was added,And stirred for 2 hours.The ethyl acetate layer was separated, dehydrated with anhydrous sodium sulfate and concentrated, and then 50 g of toluene,12 g of 2-[2-(2,2,2-trifluoroethoxy)phenoxy] ethanol-1-methanesulfonate,3.3 g of sodium carbonate was added, and the mixture was stirred under reflux.After completion of the reaction, an aqueous solution of sodium hydrogencarbonate and ethyl acetate were added, layered and then dehydrated with anhydrous sodium sulfateAnd concentrated under reduced pressure to give 2,3-dihydro-1-[3-(benzoyloxy)propyl]-5-[(2R)-2-[(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-1H-indole-7-carbonitrile (Purity: 79.9%, dialkyl content: 12.0%).

The synthetic route of 239463-85-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hanseo Chem Co., Ltd.; Oh Min-geun; Kim Gi-nam; Seo Gi-hyeong; Park Seong-tae; Cho Dong-ho; (17 pag.)KR2016/109736; (2016); A;,
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 181140-34-1 as follows. Recommanded Product: 181140-34-1

A mixture of 2,3-dihydro-1 /-/-inden-2-amine (5.0 g, 24.61 mmol) and (R)-2-(oxiran-2- ylmethyl)isoindoline-1 ,3-dione (4.91 g, 36.91 mmol) in EtOH (100 mL) was heated at reflux overnight. After cooling to room temperature, triethylamine (9.94 g, 98.44 mmol) and (0472) (Boc)20 (10.74 g, 49.22 mmol) were added and the reaction mixture was stirred at room temperature overnight. The mixture was concentrated and purified by column (EtOAc / petroleum ether = 1/4, v/v) to give the title compound (5.4 g, 50%) as an oil.

According to the analysis of related databases, 181140-34-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CTXT PTY LIMITED; STUPPLE, Paul Anthony; (88 pag.)WO2017/153519; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 552330-86-6, A common heterocyclic compound, 552330-86-6, name is 5-Bromoisoindolin-1-one, molecular formula is C8H6BrNO, 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.

Prepared using method described in Example 4, step (a) with the solution being initially irradiated for 90 min and then a further 90 min using 5-cyclopropyl-6-methyl-7-(tetramethyl- 1 ,3,2-dioxaborolan-2yl)-oxazolo[4,5-c]quinolin-4-one (Intermediate D) and 5-bromo-2,3- dihydro-1 H-isoindol-1-one. Chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 , 1 ‘- biphenyl)[2-(2’-amino-1 , 1 ‘-biphenyl)]palladium(ll) (10% mmol) was used as catalyst and .2- dicyclohexylphosphino-2′,4′,6’-triisopropylbiphenyl (10% mmol) as ligand. Column chromatography was carried out, eluting with 0-20% MeOH in DCM. 1 H NMR (Method A) (CDCb): delta ppm 8.10 (s, 1 H), 7.99 (d, J = 7.8 Hz, 1 H), 7.81 (d, J = 7.9 Hz, 1 H), 7.53 (d, J = 8.0 Hz, 1 H) 7.50 (s, 1 H), 7.28 (s, 1 H), 6.22 (s, 1 H), 4.56 (s, 2H), 3.69- 3.61 (m, 1 H), 2.54 (s, 3H), 1.33 (d, J = 6.8 Hz, 2H) 0.74 – 0.66 (m, 2H); LC-MS (Method D) 372.0 [M+H]+; RT 1.96 min

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; REDX PHARMA PLC; HUXLEY, Anthony; KIRK, Ralph; RATCLIFFE, Andrew; LYTH, David; (112 pag.)WO2017/46605; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 954-81-4, 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. 954-81-4 name is N-(5-Bromopentyl)phthalimide, 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.

To a stirred solution of compound 14-k (80 g, 0.27 mol) in DMF (745 mL) was added potassium thioacetate (34 g, 0.29 mol) portion wise over 20 mm at room temperature. After complete addition, the reaction mixture was stirred at room temperature for 30 mm. Reaction progress was monitored by TLC; after completion the reaction mixture was quenched with ice-cold water (1 L) and stirred for 1 h. The resultant precipitate was filtered, washed with water (500 mL) and dried in vacuo to afford 15-k as an off-white solid (75 g, 95%).?HNMR (400 IVIFIz, CDC13): 7.84 (dd, J= 5.5 Hz, 3.0 Hz, 2H), 7.71 (dd, J 5.5 Hz, 3.1 Hz, 2H), 3.67 (t, J= 7.3 Hz, 2H), 2.85 (t, J= 7.3 Hz, 2H), 2.30 (s, 3H), 1.73-1.65 (m, 3H), 1.64-1.57 (m, 1H), 1.46-1.37 (m, 2H);LC-MS: 292.2 (M+1).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, N-(5-Bromopentyl)phthalimide, and friends who are interested can also refer to it.

Reference:
Patent; CV6 THERAPEUTICS (NI) LIMITED; SPYVEE, Mark; LADNER, Robert, D.; (340 pag.)WO2018/98207; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 18711-15-4, name is 4,6-Dichloroisatin, 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. category: indolines-derivatives

Reference Example 23 4,6-Dichloro-3-hydroxy-3-(2-naphthyl)oxindole To a solution of 2-bromonaphthalene (2.952 g) in anhydrous THF (25 mL) was added portion wise a solution of n-butyl lithium in n-hexane (1.55 N, 10.12 mL) at -78 C. The reaction solution was stirred for 30 minutes. To the mixture was then added portion wise a solution of 4,6-dichloroisatin (1.54 g) in anhydrous THF (25 ml) for 50 minutes. The reaction mixture was stirred for 2 hours. Then the mixture was allowed to warm to room temperature. To the mixture was added 1N HCl and extracted by ethyl acetate. The organic phase was separated, washed with 1N HCl and brine and dried over MgSO4 and concentrated. Purification was carried out by silica gel chromatography (hexane:ethyl acetate, 2:1 to 1:1 gradient) to give the title compound (0.652 g, yield: 27%). 1H NMR (DMSO-d6, 300 MHz) delta 6.93 (1H, s), 6.96 (1H, d, J=1.7 Hz), 7.12 (1H, d, J=1.7 Hz), 7.23 (1H, m), 7.49 (2H, m), 7.80-7.94 (4H, m), 10.80 (1H, brs).

The synthetic route of 4,6-Dichloroisatin has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sumitomo Pharmaceuticals Co., Ltd.; US6576656; (2003); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem