Month: June 2021

Synthetic Route of 102359-00-2, A common heterocyclic compound, 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, molecular formula is C9H7NO3, 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.

Into a 10-mL round-bottom flask was placed 2-oxo-2,3-dihydro-1H-indole-5- carboxylic acid (48 mg, 0.27 mmol, 2.00 equiv), 1-hydroxybenzotrizole (40 mg, 1.26 mmol, 2.00 equiv), triethylamine (50 mg, 0.49 mmol, 4.00 equiv), N-[4-[(2S,4S)-4- amino-2-methylpiperidine-1-sulfonyl]phenyl]acetamide (40 mg, 0.13 mmol, 1.00 equiv), and dichloromethane (4 mL). N-(3-dimethylaminopropyl)-N?-ethylcarbodiimide hydrochloride (56 mg, 0.29 mmol, 2.00 equiv) was added batchwise at 0-5oC. The resulting solution was stirred for 16 hours at 25oC. The mixture was then washed with 3×5 mL of brine and the organic layer concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (2-Waters 2767-2(HPLC- 08)): Column, Xbridge Shield RP 18, 5um, 19*150mm; mobile phase, water with 50mmol NH4HCO3and CH3CN (10.0% CH3CN up to 28.0% in 2 min, up to 46.0% in 10 min,up to 100.0% in 1 min, down to 10.0% in 1 min); Detector, UV 254 nm. This resulted in 2.6 mg (4%) of N-[(2S,4S)-1-[(4-acetamidobenzene)sulfonyl]-2- methylpiperidin-4-yl]-2-oxo-2,3-dihydro-1H-indole-5-carboxamide as a white solid

The synthetic route of 102359-00-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Epizyme, Inc.; Poley, Megan Allen Clunan; Kunz, Kevin Wayne; Mills, James Edward John; Mitchell, Lona Helen; munckhof, Michael John; Harvey, Darren Martin; (303 pag.)KR2017/45749; (2017); A;,
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. 99365-40-9, name is 6-Bromoindolin-2-one, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C8H6BrNO

Sodium bis(trimethylsilyl)amide (1.0M in tetrahydrofuran, 9.40 mL, 9.40 mmol) was added dropwise to a stirred suspension of 6-bromoindolin-2-one (preparation 1, 0.40 g, 1.89 mmol) in tetrahydrofuran (4 mL) at -78C. The mixture was stirred for 30 minutes, then 2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride (0.36 g, 1.89 mmol) was added and the mixture was warmed to room temperature. After stirring overnight, water was added to the reaction and the mixture was extracted with ethyl acetate. The organic layer was dried (MgSO4) and evaporated. Purification of the residue by reverse phase chromatography (0% CH3CN in H2O to 100% CH3CN in H2O) gave the title compound as a yellow oil (0.17 g, 31%). LRMS (m/z): 295/297 (M+1)+. 1H-NMR delta (DMSO-d6): 1.68-1.86 (m, 4H), 2.51-2.62 (m, 4H), 2.80-2.87 (s, 3H), 7.00 (s, 1H), 7.14 (d, J=6.0 Hz, 1H), 7.41 (d, J=6.0 Hz, 1H), 8.28 (brs, 1H).

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 99365-40-9.

Reference:
Patent; Laboratorios Almirall, S.A.; EP2108641; (2009); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 3484-35-3, 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. 3484-35-3 name is 5-Methylindolin-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.

General procedure: A reaction mixture of compound 19-21 (2.35 mmol),compound 14-18 (2.14 mmol) and 2 drops of piperidine was stirred at RT for 3 h. The precipitate was filtered off and dried. The crude compound was purified by column chromatography using ethyl acetate in dichloromethane (13%) to afford the desired products (4, 22-32).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Methylindolin-2-one, and friends who are interested can also refer to it.

Reference:
Article; Dai, Hou-Ling; Gao, Li-Xin; Yang, Ying; Li, Jing-Ya; Cheng, Jia-Gao; Li, Jia; Wen, Ren; Peng, Yan-Qing; Zheng, Jian-Bin; Bioorganic and Medicinal Chemistry Letters; vol. 22; 24; (2012); p. 7440 – 7443;,
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. 59-48-3, name is Indolin-2-one, A new synthetic method of this compound is introduced below., HPLC of Formula: C8H7NO

Preparation of 5-Nitro-2-indolinone The 2-indolinone (6.5 g) was dissolved in 25 mL of concentrated sulfuric acid and the mixture maintained at -10-15 C. while 2.1 mL of fuming nitric acid was added dropwise. After the addition of the nitric acid the reaction mixture was stirred at 0 C. for 0.5 hr and poured into ice-water. The precipitate was collected by filtration,. washed with water and crystallized from 50% of acetic acid. The final crystal was then filtered, washed with water and dried under vacuum to give 6.3 g (70%) of 5-nitro-2-indolinone.

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; Sugen, Inc.; US6316635; (2001); B1;,
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. 264916-06-5, name is tert-Butyl 5-aminoisoindoline-2-carboxylate, A new synthetic method of this compound is introduced below., Computed Properties of C13H18N2O2

(2) 2-tert-Butoxycarbonyl-5-(2-nitrophenylamino)isoindoline A dimethylformamide (10 ml) suspension of 5-amino-2-tert-butoxycarbonylisoindoline (5.3 g, 22.6 mmol), o-fluoronitrobenzene (7.15 ml, 22.6 mmol) and potassium carbonate (3.12 g, 22.6 mmol) was stirred at 145 C. for 2 hours under nitrogen atmosphere. After cooling, the reaction mixture was diluted with ethyl acetate and washed with water. After drying over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography to give 2-tert-butoxycarbonyl-5-(2-nitrophenylamino)isoindoline (4.9 g, 61%) as an oil. 1H-NMR(CDCl3) delta: 1.53(9H, s), 4.67(2H, s), 4.70(2H, s), 6.76(1H, t, J=6.8 Hz), 7.15-7.41(5H, m), 8.20(1H, d, J=8.8 Hz), 9.47(1H, bs).

The synthetic route of 264916-06-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Oi, Satoru; Suzuki, Nobuhiro; Matsumoto, Takahiro; US2003/149027; (2003); 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. 5332-26-3, name is 2-(Bromomethyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-(Bromomethyl)isoindoline-1,3-dione

General procedure: After the compound 1o (700 mg, 1.68 mmol) was dissolved in dichloromethane (15 mL), potassium hydroxide (278 mg, 4.22 mmol) and tetrabutylammonium bromide (60 mg) were added thereto, and iodomethyl (0.525 mL, 8.435 mmol) was slowly added thereto at room temperature. This solution was stirred for 10 hours at 25C. Cooling water was added to the reaction material, and the result was adjusted to pH 5 to 6 using a 2N aqueous hydrochloric acid solution. After the organic layer was separated and taken, the aqueous layer was extracted once with dichloromethane, and the organic layers were combined, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated using silica gel column chromatography (normal-hexane/ethyl acetate=4/1) to give a pure target compound 1z (574 mg, 79%). 1H-NMR (300 MHz, CDCl3) delta 0.97 (s, 9H), 1.49 (s, 3H), 2.28 (s, 3H), 2.71 (s, 3H), 3.65 (s, 3H), 3.75 (s, 3H), 5.07 (s, 1H), 7.24 (m, 1H), 7.43 (m, 3H); MS (EI, m/e)=428 (M+). A target compound 19a (780 mg, 94%) was obtained by reacting the compound 1o (600 mg, 1.446 mmol) inthe same manner as in Step 1 of Example 1, except that N-(bromomethyl)phthalimide (787 mg, 3.0 equivalents) andpotassium hydroxide (400 mg, 5 equivalents) were used instead of iodomethyl and the stirring was carried out for 7hours at 20C. 1H-NMR (300 MHz, CDCl3) delta 0.98 (s, 9H), 1.46 (s, 3H), 2.45 (s, 3H), 2.65 (s, 3H), 3.63 (s, 3H), 5.04 (s, 1H),6.08 (AB-q, 2H), 7.24 (m, 2H), 7.37 (m, 2H), 7.73 (m, 2H), 7.68 (m, 2H); MS (EI, m/e)=573 (M+).

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:
Patent; Korea Research Institute of Chemical Technology; SON, Jong Chan; KIM, Bong Jin; KIM, Jae Hak; LEE, Ill Young; YUN, Chang Soo; LEE, Sang Ho; LEE, Chong Kgo; (98 pag.)EP2781519; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 102359-00-2,Some common heterocyclic compound, 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, molecular formula is C9H7NO3, 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.

Reference Example 15 Production of 5-(5-phenyloxazol-2-yl)indolin-2-one To a solution of 2-oxoindoline-5-carboxylic acid (1.3 g, 7.3 mmol) in DMF (50 ml) was added iPr2NEt (3.8 ml, 22 mmol), HOBt (1.2 g, 8.8 mmol), WSCI (1.7 g, 8.8 mmol) and 2-amino-1-phenylethanone hydrochloride (1.3 g, 7.3 mmol). The reaction mixture was stirred for 2 h at room temperature. The mixture was poured into H2O and EtOAc. The resulting precipitate was removed by filtration, and the filtrate was separated. The organic layer was washed with sat. NaHCO3 solution, sat. NH4Cl solution and brine, and then dried over Na2SO4. The solvent was evaporated and the residue (0.73 g) was used for the next reaction without further purification. Sulfuric acid (5 ml) was added to the residue, and the mixture was heated for 2 h at 100 C. Ice was added, and the mixture was extracted with EtOAc. The organic layer was washed with H2O and brine, dried over Na2SO4 and evaporated. The residue was crystallized from EtOH to afford 5-(5-phenyloxazol-2-yl)indolin-2-one (0.27 g, 13%). 1H NMR (300 MHz, DMSO-d6) delta 10.68 (s, 1H), 7.96-7.91 (m, 2H), 7.84-7.80 (m, 2H), 7.77 (s, 1H), 7.52-7.47 (m, 2H), 7.37 (m, 1H), 6.97 (d, 1H, J=8.0 Hz), 3.60 (s, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Oxoindoline-5-carboxylic Acid, its application will become more common.

Reference:
Patent; Tsuboi, Katsunori; Takanashi, Yosuke; Tojo, Shingo; Kodama, Tomohiro; Kubota, Katsumi; Kanai, Toshio; US2014/275076; (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

Compound 5 (28.29 g, 167.4 mmol) and DMA (65 mL) were added to compound 4 (20.00 g, 104.6 mmol) and stirred.After warming the reaction solution to 40 C., sodium tert-butoxide (15.09 g, 157.0 mmol) was slowly added.The reaction solution was stirred at 40 C for 3 hours and then cooled to 20 C.Acetic acid (3.14 g) and 10% saline (64 g) were added to the reaction solution,And extracted twice with ethyl acetate (60 mL). Water (144 mL) was added to the organic layer and the mixture was cooled to 0 C.The resulting pale yellowish white precipitate was collected by filtration.The resulting solid was washed with a mixture of methanol (5.4 g) and water (48.6 g)And dried to obtain Compound 6 (20.44 g, yield 78%) as a pale yellowish 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:
Patent; SHIONOGI & COMPANY LIMITED; SHIBAHARA, SETSUYA; FUKUI, NOBUAKI; MAKI, TOSHIKATSU; (38 pag.)JP6212678; (2017); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 317-20-4, These common heterocyclic compound, 317-20-4, name is 7-Fluoroisatin, 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 isatins 1 (1 mmol), substituted 1H-pyrazol-5-amine 2 (1 mmol), 6-aminopyrimidine-2,4(1H,3H)-dione 3 or 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione 5 (1 mmol), H2O(6 mL), and HOAc (2 mL) was placed in a 25-mL flask andstirred at 90 C (monitored by thin layer chromatography (TLC)) for about 7 h. Afterreaction completion, the mixture was cooled to room temperature and the precipitateobtained by filtration. Compounds 4 or 6 were further purified by recrystallizationfrom DMF.

Statistics shows that 7-Fluoroisatin is playing an increasingly important role. we look forward to future research findings about 317-20-4.

Reference:
Article; Dai, Lei; Mao, Kaimin; Pan, Zhengbing; Rong, Liangce; Research on Chemical Intermediates; vol. 45; 2; (2019); p. 769 – 788;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 25369-33-9, name is 7-Chloroindolin-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 25369-33-9, Quality Control of 7-Chloroindolin-2-one

Example 24; Preparation of (Z)-3-(azulen-1-ylmethylene)-7-chloroindolin-2-one(042); 0.3519g 7-chlorooxindole (0.0021mole) and 0.323g azulene aldehyde (0.0021mole) were dissolved in 30mL dried ethanol. 1.5mL pyrrolidine (1M) was then added and uniformly stirred at reflux temperature for two hours. After removal of dried ethanol, the results were extracted by dichloromethane and citric acid aqueous solution. The organic layer was collected, dried with anhydrous magnesium sulfate, filtered, concentrated under vacuum, and separated by silica gel column chromatography to give Z-form Compound 042 (0.3693g). The total weight of 7-chlorooxindole-azulene was 0.3693g (57.56%). 042 (500 MHz, DMSO-d6) delta (ppm) 10.89 (s, 1H), 9.75 (d, J=4.5 Hz, 1H), 9.25 (d, J=10.0 Hz, 1H), 8.57 (d, J=10.0 Hz, 1H), 8.48 (s, 1H), 7.97 (d, J=7.5 Hz, 1H), 7.94 (t, J=10.0 Hz, 1H), 7.61 (t, J=10.0 Hz, 1H), 7.60 (d, J=4.5 Hz, 1H), 7.55 (t, J=10.0 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.03 (d, J=7.5 Hz, 1H). LC-MS (m/z) 306 [M+1].

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; Industrial Technology Research Institute; EP1918277; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem