Month: March 2021

Synthetic Route of 1504-06-9, These common heterocyclic compound, 1504-06-9, name is 3-Methyloxindole, 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.

To a 10 mL Schlenk flask was added 3-methyl 2-indolone (0.2 mmol),Tert-butyl nitrite (t-BuONO, 0.4 mmol) and 1,4-dioxane (2 mL). The reactor was then stirred at 25 C. The reaction progress was monitored by TLC or GC until the reaction mass 3-methyl-2-indolone reaction is complete, The reaction was quenched with saturated brine and the organic phase was recovered. The aqueous phase was extracted with ethyl acetate and the organic phases were combined. The organic phase was dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure.The residue was subjected to column chromatography (n-hexane / ethyl acetate) to give the target product 3-nitro-2-indolinone derivative I-2 in a yield of 71%

The synthetic route of 1504-06-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Ningbo University; Wu Yi; Wei Wenting; Zhu Wenming; Huang Yiling; Wu Kewei; Cao Yiqi; Wang Yining; Zhu Liwei; (7 pag.)CN107200705; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 32692-19-6, 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.

1) Production of N,N-dimethyl-2-(5-nitro-2,3-dihydro-1H-indol-1-yl)ethylamine: 730 mg of sodium hydride was added to an N,N-dimethylformamide solution of 1 g of 5-nitroindoline, and stirred at room temperature for 30 minutes. 1.8 g of 2-dimethylaminoethyl chloride hydrochloride was added to the reaction liquid, and stirred at 70C for 1 hour. The reaction liquid was cooled, diluted with chloroform, and washed with aqueous saturated sodium bicarbonate solution and saturated saline water in that order. The organic layer was dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The resulting crude product was purified through basic silica gel column chromatography (chloroform/methanol) to obtain 950 mg of the entitled compound as a yellow oil. 1H-NMR (CDCl3) delta: 8.26 (1H, dd, J=8.8, 2.4 Hz), 8.14 (1H, d, J=2.4 Hz), 6.96 (1H, d, J=8.8 Hz), 3.88 (2H, t, J=6.8 Hz), 3.64 (2H, s), 2.57 (2H, t, J=6.8 Hz), 2.30 (6H, s) ESI-MS Found: m/z [M+H] 250

The synthetic route of 32692-19-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Banyu Pharmaceutical Co., Ltd.; EP2168966; (2010); A1;,
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. 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C10H9NO3

To a solution of 2-(2-hydroxyethyl)isoindoline-1,3-dione (1.68 mmol) in methylene chloride (10 mL) was added ADDP (1.68 mmol), triphenylphosphine (1.68 mmol) and phenol (3.18 mmol) and stirred at room temperature. After stirring overnight, the reaction mixture was diluted with methylene chloride (30 mL) and washed with 1 M NaOH aqueous solution (50 mL), and brine (50 mL). The organic layer was dried over anhydrous MgSO4 and concentrated in vacuo. The crude product was purified by silica gel flash column chromatography (4:1 hexanes/ethyl acetate) and recrystallized from a mixture of hexanes and ethyl acetate to give A1.

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 3891-07-4.

Reference:
Patent; Brodin, Priscille; Christophe, Thierry; No, Zaesung; Kim, Jaeseung; Genovesio, Auguste; Fenistein, Denis Philippe Cedric; Jeon, Heekyoung; Ewann, Fanny Anne; Kang, Sunhee; Lee, Saeyeon; Seo, Min Jung; Park, Eunjung; Contreras Dominguez, Monica; Nam, Ji Youn; Kim, Eun Hye; US2011/178077; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 61-70-1, 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 61-70-1 as follows.

To a round-bottom flask containing a solution of N-methyl-2-oxindole (4.85 g, 33 mmol) in acetic anhydride (36 mL, 381 mmol), DMAP (118 mg, 0.96 mmol) was added. The mixture was heated at 140 C for 5 h. The mixture was evaporated under reduced pressure, the crude residue was dissolved in MeOH (80 mL) and a solution of KOH (18 g, 321 mmol) in MeOH (120 mL) at 0 C was added. The solution was stirred at r.t. for 22 h then cooled in an ice-bath at 0 C and 12 M aqueous HCl was added until pH 3. At this point, H2O (140 mL) was added and the solution was extracted with EtOAc (3 140 mL). The organic phases were dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (hexane/EtOAc) to give pure 2a. Yield: 5.5 g (88%); purple solid; mp 109-110 C (hexane/EtOAc) (Lit. 12 110-111 C).

According to the analysis of related databases, 61-70-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Ortega-Martinez, Aitor; Molina, Cynthia; Moreno-Cabrerizo, Cristina; Sansano, Jose M.; Najera, Carmen; Synthesis; vol. 49; 23; (2017); p. 5203 – 5210;,
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. 496-12-8, name is Isoindoline belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. COA of Formula: C8H9N

3 – ((2S, 3R, 4R, 5S, 6R) -3,4,5-triacetoxy-6-acetoxymethyl-tetrahydropyran- 2- yl] benzylaldehyde 925 milligrams (2.12 millimoles) were dissolved in 20 milliliters of dichloroethane, To the reaction mixture was added 292 mg of isoindoline (2.45 mmol), 254 mg of acetic acid (4.24 mmol) and sodium triacetoxyborohydride 674 milligrams (3.18 millimoles) was added and the drug And stirred at 20 [deg.] C for about 3 hours. The reaction mixture solution was heated to 0 o After cooling to C, saturated sodium bicarbonate And then extracted with ethyl acetate. The organic solution was dried over anhydrous magnesium sulfate and filtered The reaction mixture was concentrated and then purified by column chromatography to obtain the compound 850 mg (yield: 74.6%) was obtained Method B)

The synthetic route of 496-12-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Samjin Pharmaceutical Co., Ltd.; Cho, Eui-Hwan; Shin, Hui-Jong; Kwon, Ho-Seok; Lee, Jae-Woong; Joo, Jeong-Ho; Lee, Keun-Kuk; Kim, Jong-Min; Kim, Hyun-Tae; Kim, Jae-Eon; Lee, Jung-Rok; Jang, Beom-Hyeon; (37 pag.)KR2016/97861; (2016); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 150560-58-0, 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. 150560-58-0, name is 5-Isopropylindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Example 11A 6-Isopropyl-3-methyl-2-phenylquinoline-4-carboxylic acid (0396) (0397) 2.50 g (13.21 mmol) of 74 5-isopropyl-1H-indole-2,3-dione were initially charged together with 36 ml of 41 acetic acid and 1.77 g (13.21 mmol) of 40 1-phenylpropan-1-one, and the reaction mixture was stirred at 75 C. for 5 min. Then 12 ml of 42 conc. hydrochloric acid were added, and stirring of the mixture was continued at 105 C. overnight. After cooling to RT, the reaction mixture was added to 500 ml of 1 M hydrochloric acid and the precipitated solids were filtered off. The solids were washed with water and dried under reduced pressure. 2.04 g (31% of theory, 62% purity) of the 75 title compound were obtained. (0398) LC/MS (Method 1, ESIpos): Rt=0.66 min, m/z=306 [M+H]+.

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-Isopropylindoline-2,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Bayer Pharma Aktiengesekkschaft; BECK, Hartmut; THALER, Tobias; KAST, Raimund; MEIBOM, Daniel; MEININGHAUS, Mark; TERJUNG, Carsten; DELBECK, Martina; LUSTIG, Klemens; MUENSTER, Uwe; OLENIK, Britta; (100 pag.)US2017/260140; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 2436-29-5, 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. 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

< 1 - 12> 2- { 3-[4-(4-bromo-2-fluoro-pheny lamino)-7-( 1 -methyl-piperidin-4- ylmethoxy)-quinazolin-6-ylamino]-propyl}-isoindol-l,3-dione; The compound of (2.0 g, 0.0043 mol) was dissolved in 40 ml of ethanol, the compound of <1-11> (1.3 g, 0.0064 mol) and sodium cyanoborohydride (500 mg, 0.0086 mol) were added thereto, and stirred at room temperature for 6 hours after adding a catalytic amount (1 m-C) of acetic acid thereto. When the reaction was terminated, the reacted solution was distilled under a reduced pressure, and saturated sodium bicarbonate solution was added thereto. The resulting solution was extracted with dichloromethane, dried over magnesium sulfate, and distilled under a reduced pressure. The resulting residue was subjected to column chromatography to obtain the title compound 1.3 g (yield: 46%). 1H NMR (CDCl3) delta: 8.56 (s, IH), 8.41 (t, IH), 7.81-7.68 (m, 4H), 7.34-7.30 (m, 2H), 7.06 (s, IH), 6.63 (s, IH), 5.03 (br, NH), 4.00 (d, 2H), 3.85 (t, 2H), 3.36 (d, 2H), 2.96 (d, 2H), 2.3 (s, 3H), 2.14-2.02 (m, 3H), 2.00-1.88 (m, 2H), 1.59-1.53 (m, 2H).

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

Reference:
Patent; HANMI PHARM. CO., LTD.; WO2007/55513; (2007); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 337536-15-9, name is 4-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. Product Details of 337536-15-9

General procedure: Step 1: A glass vial was charged with corresponding bromo-heteroaryl compound (0.20mmol, 1eq), potassium metabisulfite (88mg, 0.40mmol, 2eq), tetrabutylammonium bromide (70mg, 0.22mmol, 1.1eq), sodium formate (15mg, 0.22mmol, 1.1eq), palladium(II) acetate (5mg, 0.02mmol, 0.1eq), triphenylphosphine (16mg, 0.06mmol, 0.3eq), 1,10-phenanthroline (11mg, 0.06mmol, 0.3eq). After sealing, the vial was flushed with argon for 30min and the reagents were suspended in dry, degassed DMSO (1mL) and the reaction mixture was stirred for 4h at 70C. After cooling to RT N,N-Diisopropylethylamine (70muL, 0.40mmol, 2eq) and a solution of tert-butyl (E)-(2-aminoethyl)(3-(4-(pyridin-3-yl)phenyl)allyl)carbamate (63) (106mg, 0.30mmol, 1.5eq) in dry THF (1mL) were added and the reaction mixture was cooled to 0C. Subsequently a solution of N-bromosuccinimide (62mg, 0.40mmol, 2eq) in dry THF (1mL) was added and the reaction mixture was allowed to come to RT. After stirring for 1h the reaction was quenched by adding H2O (1mL) and brine (2mL). The resulting mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the solvent removed under reduced pressure. The residue was purified via flash-column-chromatography (SiO2, 0% to 5% MeOH in DCM) to yield the desired Boc-protected product, which was used directly in step 2.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 337536-15-9, its application will become more common.

Reference:
Article; Grimm, Sebastian H.; Gagestein, Berend; Keijzer, Jordi F.; Liu, Nora; Wijdeven, Ruud H.; Lenselink, Eelke B.; Tuin, Adriaan W.; van den Nieuwendijk, Adrianus M.C.H.; van Westen, Gerard J.P.; van Boeckel, Constant A.A.; Overkleeft, Herman S.; Neefjes, Jacques; van der Stelt, Mario; Bioorganic and Medicinal Chemistry; vol. 27; 5; (2019); p. 692 – 699;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, A new synthetic method of this compound is introduced below., HPLC of Formula: C10H9NO3

EXAMPLE 1 Preparation of Ethyl 4-(2-(Phthalimido)Ethoxy)Acetoacetate (Formula V) 300 liters of toluene was taken into a clean and dry reactor and 50 Kg of sodium hydride was added under a nitrogen atmosphere. 50 Kg of [N-{2-hydroxyethyl}] phthalimide was added to the reactor and the resultant reaction mass was subjected to agitation and heating to 57 C. The reaction mass was maintained at 56-57 C. for 30 minutes. Another 50 Kg of [N-{2-hydroxyethyl}] phthalimide was added to the above reaction mass in 18 lots of 2.7 kg each and a further lot of 1.4 kg, at 60 C. Liberation of hydrogen was observed. The reaction mass was maintained at 57 C. until hydrogen gas liberation ceased. A solution of 94 Kg of ethyl 4-chloroacetoacetate in 287 liters of toluene was added to the above reaction mass at 57 C. and maintained at the same temperature for 20 minutes. The reaction mass was then cooled to 30 C. and then further cooled to 17 C. 200 liters of glacial acetic acid was added to the above obtained reaction mass in three equal lots at 17 C. and stirred for 30 minutes. 1000 liters of water was added to the reaction mass and stirred for 20 minutes. The organic layer was separated and the aqueous layer was extracted into 220 liters of toluene. The combined toluene layer was progressed to the next stage.

The synthetic route of 3891-07-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bolugoddu, Vijayabhaskar; Dahyabhai, Jaydeepkumar Lilakar; Pingili, Ramachandra Reddy; Veeraboina, Madhu Raju; Gade, Srinivas Reddy; Mallepalli, Srinivas Reddy; Amirisetty, Ravindranath Tagore; US2007/260065; (2007); A1;,
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. 496-12-8, name is Isoindoline, This compound has unique chemical properties. The synthetic route is as follows., name: Isoindoline

General procedure: A mixture of tert-butyl (2-amino-1-(thiophen-3-yl)ethyl)(methyl)carbamate (33) (310 mg, 1.21 mmol) and N,N-diisopropylethylamine (300 muL, 1.73 mmol) in CH2Cl2 (15 mL) was purged with argon and cooled to 0 C. A solution of 4-nitrophenylchloroformate (244 mg, 1.21 mmol) in CH2Cl2 (5 mL) was added, and resulting reaction mixture was stirred at – 70 C for 30 min. After this time, 5-fluoroisoindoline hydrochloride (150 mg, 0.86 mmol) was added, followed by N,N-diisopropylethylamine (450 muL, 2.60 mmol). The resulting mixture was stirred for 20 h at room temperature. A saturated NaHCO3 solution (10 mL) was added, and the resulting suspension was extracted with CH2Cl2 (3 x15 mL). The combined organic extracts were washed with water (30 mL), then with a brine solution (20 mL) and dried over solid anhydrous Na2SO4. After filtration, the volatiles were removed in vacuo, and the residue was purified by flash chromatography using eluent from CH2Cl2 to CH2Cl2/MeOH (1:1), then reverse phase chromatography using eluent from H2O/MeCN (9:1) MeCN, to give tert-butyl (2-(5-fluoroisoindoline-2-carboxamido)-1-(thiophen-3- yl)ethyl)(methyl)carbamate (34) (150 mg, 41% yield). 300 MHz 1H-NMR (CDCl3, ppm): 7.32 (dd, J=5.0, 2.9 Hz, 1H) 7.24-7.14 (m, 2H) 7.05-6.91 (m, 3H) 5.63-5.41 (m, 1H) 5.09- 4.91 (m, 1H) 4.68 (s, 2H) 4.64 (s, 2H) 4.15-3.88 (m, 1H) 3.77-3.57 (m, 1H) 2.56 (s, 3H) 1.45 (s, 9H); ESI-MS (m/z): 420 [M+H]+; melting point: 182-184 C. Isoindoline (500 mg, 4.20 mmol) and tert-butyl (2-amino-1-phenylethyl)(methyl) carbamate (36) were reacted in CH2Cl2 using procedure described for compound (34) to obtain tert-butyl (2-(isoindoline-2-carboxamido)-1-phenylethyl)(methyl)carbamate (37) (1.49 g, 90% yield). 400 MHz 1H-NMR (CDCl3, ppm): 7.41-7.33 (m, 2H) 7.33-7.29 (m, 2H) 7.29- 7.23 (m, 5H) 5.62-5.41 (m, 1H) 5.19-5.00 (m, 1H) 4.71 (s, 4H) 4.19-3.93 (m, 1H) 3.84-3.62 (m, 1H) 2.55 (s, 3H) 1.46 (s, 9H); ESI-MS (m/z): 396 [M+H]+.

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 496-12-8.

Reference:
Patent; MEBIAS DISCOVERY LLC; TOUNGE, Brett A.; BAYOUMY, Shariff; KUO, Lawrence C.; DAX, Scott; (93 pag.)WO2018/45229; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem