Month: March 2021

Application of 17564-64-6, The chemical industry reduces the impact on the environment during synthesis 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-dione, I believe this compound will play a more active role in future production and life.

General procedure: The initial carbonyl compound (50 mmol) was dissolved/suspended in ethanol (50 mL) and magnetically stirred with thiosemicarbazide (50 mmol) and catalytic amounts of acetic acid for 8-24 h at room temperature. The obtained thiosemicarbazone was filtered, washed with appropriate solvent (n-hexane, petroleumether or diethyl ether) and dried under vacuum. The intermediate thiosemicarbazone (50 mmol) reacted with ethyl bromoacetate (50 mmol), in methanol (50 mL) and sodium acetate (50 mmol) at room temperature under magnetic stirring for 24 h. The resulting 4-thiazolidinone was poured on ice, filtered or extracted with chloroform (3 x 100 mL) and purified by column chromatography (SiO2, ethyl acetate/n-hexane). Then, the obtained thiazolidinone (50 mmol) was dissolved/suspended in 50 mL of anhydrous acetone in the presence of anhydrous potassium carbonate (50 mmol), and reacted with equimolar amounts of 4-nitrobenzyl bromide, 1-(chloromethyl)naphthalene and N-(chloromethyl)phthalimide for 24-48 h. The product was poured on ice, filtered or extracted with chloroform (3 x 50 mL) and purified by column chromatography (SiO2, ethyl acetate/n-hexane) in order to obtain the title compoundsin high yields. 7.1.58 2-((2-(2-(4-Methylpentan-2-ylidene)hydrazono)-4-oxothiazolidin-3-yl)methyl)isoindoline-1,3-dione (6C) Yellow powder, mp 66-67 C, 75% yield; 1H NMR (400 MHz, DMSO-d6): delta 0.91-0.92 (d, J = 6.8 Hz, 6H, 2 * CH3), 1.91 (s, 3H, CH3), 1.94-2.01 (m, 1H, CH), 2.14-2.16 (d, J = 7.2 Hz, 2H, CH2), 3.82 (s, 2H, CH2, thiazolidinone), 5.73 (s, 2H, ArCH2), 7.74-7.80 (m, 2H, Ar), 7.86-7.88 (m, 2H, Ar).

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, 2-(Chloromethyl)isoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Article; De Monte, Celeste; Carradori, Simone; Bizzarri, Bruna; Bolasco, Adriana; Caprara, Federica; Mollica, Adriano; Rivanera, Daniela; Mari, Emanuela; Zicari, Alessandra; Akdemir, Atilla; Secci, Daniela; European Journal of Medicinal Chemistry; vol. 107; (2016); p. 82 – 96;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 6941-75-9, A common heterocyclic compound, 6941-75-9, name is 5-Bromoisoindoline-1,3-dione, molecular formula is C8H4BrNO2, 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 mixture of 4-bromophthalic anhydride (25 g) in formamide (75 ml) was heated at 2000C for 16 hours then allowed to cool to room temperature. The reaction mixture was diluted with water (200 ml), filtered, the filter cake was washed with water then diethyl ether and sucked dry to give 20.85 g of light mustard solid.280 ml of 1 M Borane-THF complex was added dropwise to a stirred solution of 4-bromophthalimide (20.85 g; 92.2 mmol) in anhydrous THF (200 ml) at O0C then heated at reflux overnight. The reaction was cooled to O0C then treated cautiously with methanol (100 ml) followed by 2M HCI (100 ml) then heated at reflux for 3 hours. The reaction mixture was cooled and the organics evaporated. The aqueous was diluted with water (100 ml) the extracted with DCM (x3). The aqueous was basified with 2M NaOH then extracted with DCM (x3). The combined DCM extracts were dried (MgSO4), filtered and evaporated to give 6.99 g of 5-bromo-2,3-dihydro-1H-isoindole as a dark brown gummy solid. 1H NMR (DMSO-d6) 7.45 (1H, s), 7.36 (1 H1 d), 7.20 (1H, d), 4.05 (4H, s).

The synthetic route of 6941-75-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2008/44054; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 954-81-4, A common heterocyclic compound, 954-81-4, name is N-(5-Bromopentyl)phthalimide, molecular formula is C13H14BrNO2, 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.

According to the Scott?s method4, ethyl acetoacetate (1.30 g, 10.0 mmol) was added to a solution of sodium ethoxide in EtOH, prepared from dist. EtOH (8 mL) and sodium (230 mg, 10.0 mmol). To the mixture was added N-(5-bromopentyl)phthalimide (4) (2.96 g, 10.0 mmol), and refluxed under argon for 6 hours. After cooling, the reaction mixture was neutralized with 2N HCl, and the ethanol was removed under reduced pressure. The residue was dissolved in H2O (50 mL), and extracted with Et2O (3 x 40 mL). The organic phase was combined, dried over Na2SO4, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane : AcOEt = 2 : 1) to give 54 (2.33 g, 79%) as a colorless oil. 1H NMR (300 MHz, CDCl3) delta 1.27 (t, 3H, J = 7.3 Hz), 1.32-1.37 (m, 4H), 1.66-1.71 (m, 2H), 1.82-1.87 (m, 2H), 2.23 (s, 3H), 3.40 (t, 1H, J = 7.3 Hz), 3.67 (t, 2H, J = 7.3 Hz), 4.20 (q, 2H, J = 7.3 Hz), 7.72 (dd, 2H, J = 5.5 Hz, 3.3 Hz), 7.84 (dd, 2H, J = 5.5 Hz, 3.3 Hz). 13C NMR (75 MHz, CDCl3) delta 13.9, 26.4, 26.8, 27.8, 28.1, 28.6, 37.6, 59.6, 61.1, 123.0, 131.9, 133.7, 168.2, 169.6, 202.9. MS (FAB) 346 (M+H)+. TLC: Rf 0.40 (Hexane : AcOEt = 2 : 1).

The synthetic route of 954-81-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Kamo, Masahiro; Tateishi, Hiroshi; Koga, Ryoko; Okamoto, Yoshinari; Otsuka, Masami; Fujita, Mikako; Bioorganic and Medicinal Chemistry Letters; vol. 26; 1; (2016); p. 43 – 45;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 496-12-8,Some common heterocyclic compound, 496-12-8, name is Isoindoline, molecular formula is C8H9N, 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 stirred solution of isoindoline (2 g, 16.8 mmol) at 0 0C5 was added slowly concentrated H2SO4 (10 mL). Then a mixture of 70% HNO3 (2.1 mL, 33.6 mmol) and concentrated H2SO4 (2 mL) was added. After addition the mixture was stirred at 00C for 30 min. The reaction mixture was poured into ice water. The mixture was carefully neutralized with 50% aq. NaOH to pH 10 and extracted with EtOAc (3 x). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to afford 5-nitroisoindoline as a brown solid. LCMS calc. = 165.1; found = 164.9 (M+H)+. 1H NMR (500 MHz5 CDCl3): delta 8.11 (d, J= 8.0 Hz, 2 H); 7.39 (d, J= 7.8 Hz, 1 H); 4.33 (s, 4 H); 2.31 (br s, 1 H).

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

Reference:
Patent; MERCK & CO., INC.; WO2007/81569; (2007); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, 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 14192-26-8, Quality Control of Methyl 2-oxoindoline-6-carboxylate

A mixture of compound VI (lOg) and acetic anhydride (40ml) was stirred at about 110C-120C for about 2h. To this reaction mass, triethyl orthobenzoate (35.18gm) was slowly added at about 115-125C for 3h and distilled out low boiler simultaneously at about 120-125C. Then the reaction mass was cooled to about 90C, and concentrated under vacuum to obtain crude compound of formula V.

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; GLENMARK PHARMACEUTICALS LIMITED; NAIK, Samir; SRIVASTAVA, Sachin; PATIL, Pramod; PATIL, Premchand Bansilal; BHIRUD, Shekhar Bhaskar; (34 pag.)WO2019/48974; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 3335-98-6, 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. 3335-98-6 name is 1-Phenyloxindole, 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.

Phosphorous oxychloride (50 mL, 538 mmol) is added slowly to a solution of DMF (50 mL) in dichloromethane (50 mL) maintaining the temperature at 5 C. After 30 min, a solution of 1-phenyl-1H-indol-2-one (25 g, 120 mmol) and pyridine (25 mL, 309 mmol) in chloroform (125 mL) is added and the reaction is stirred 48 hr at room temperature. The reaction is poured into ice water (600 mL) and the aqueous layer is separated and extracted with chloroform (3¡Á200 mL). The combined organic layer and extracts is dried, filtered and concentrated. The solid residue is crystallized from ethanol to afford 2-chloro-1-phenyl-1H-indole-3-carboxaldehyde (12.0 g, 39.25% yield) as an orange solid. NMR (CDCl3) 10.21 (1H, s), 8.37 (1H, d), 7.60 (3H, m), 7.41 (2H, m), 7.38 (1H, t), 7.28 (1H, m), 7.10 (1H, d). A second crop (7.5 g, 24.5% yield) is obtained by concentration of the filtrate and chromatography the residue eluting with dichloromethane.

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

Reference:
Patent; Aventis Pharmaceuticals Inc.; US2005/54631; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 20870-90-0, 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. 20870-90-0, name is 5-Bromo-1-methyl-2-oxoindoline belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: Under N2, sodium ( 0.5 g ) was reacted with 30 ml ethanol. When the solution was clear,2.9 g N-Me oxindole was added followed by 3.1 g diethyl carbonate and the resulting reactionmixture was refluxed for 15 hours. Then cooled to room temperature and added to 3Nhydrochloric acid solution ( pH = 2 ). The resulting solution was extracted with ether for threeEntry Catalyst time (h) yieldb(%) drc eed(%)1 3e 5 96 72:28 38e/382 3f 8 96 74:26 21e/33 3g 2 99 73:27 11e/334 3h 8 96 71:29 6e/335 3i 2 95 59:41 1e/26 3j 10 94 68:31 44/1e7 3k 2 93 67:33 1/18 3l 72 61 69:31 8/1times. The organic extracts were combined and dried over magnesium sulfate. Thenconcentrated in vacuo and washed with petroleum ether to give 2.7 g2-oxindole-3-carboxylates 1a (61%) as light 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-Bromo-1-methyl-2-oxoindoline, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Zhou, Jing; Jia, Li-Na; Peng, Lin; Wang, Qi-Lin; Tian, Fang; Xu, Xiao-Ying; Wang, Li-Xin; Tetrahedron; vol. 70; 21; (2014); p. 3478 – 3484;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

13861-75-1, name is Spiro[cyclopropane-1,3′-indolin]-2′-one, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. COA of Formula: C10H9NO

Example 3 1′-((1-isopentyl-1H-benzo[d]imidazol-2-yl)methyl)spiro[cyclopropane-1,3′-indolin]-2′-one A dried flask under nitrogen was charged with sodium hydride (120 mg, 3.0 mmol) and DMF (1 mL). This rapidly stirred suspension was cooled to 0 C. using an ice/water bath and spiro[cyclopropane-1,3′-indolin]-2′-one (160 mg, 1.0 mmol, Preparatory Example 4) was added dropwise as a solution in DMF (2 mL). The ice/water bath was removed for 15 minutes before the mixture was recooled to 0 C. and 2-(chloromethyl)-1-isopentyl-1H-benzo[d]imidazole hydrochloride (236 mg, 1.0 mmol) was added dropwise as a solution in DMF (2.1 mL). The mixture was allowed to warm to rt and stirred there for 16 hours. The mixture was cooled to 0 C. and ice was added carefully. Partition between EtOAc and water was followed by separation, drying and concentration in vacuo. Preparative HPLC gave isolation of the desired compound, (110 mg, 0.31 mmol, 31%). 1H NMR (400 MHz): delta 0.96 (d, 6H), 1.45 (m, 2H), 1.60 (m, 2H), 1.69 (m, 1H), 1.82 (m, 2H), 4.26 (m, 2H), 5.35 (s, 2H), 6.83 (d, 1H), 7.02 (dd, 1H), 7.19 (dd, 1H), 7.29 (m, 3H), 7.47 (d, 1H), 7.81 (m, 1H). LC/MS 360 (MH+).

The synthetic route of 13861-75-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; re: Viral Ltd; Cockerill, Stuart; Pilkington, Christopher; Lumley, James; Angell, Richard; Mathews, Neil; US2014/308282; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 954-81-4, These common heterocyclic compound, 954-81-4, name is N-(5-Bromopentyl)phthalimide, 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.

N-(5-bromopentyl)phthalimide (1.2g, 4mmol) and thiomorpholine 1,1-dioxide (1.08g, 80mmol) and DIPEA (2ml, 11mmol) was added 10mL i-PrOH, the temperature was raised to 105 deg. C stirred for 16 hours. LCMS traced the reaction. After completion of the reaction it was concentrated, 50ml of water was added, sonicated, and filtered to give a white solid N-(5-(1,1-dioxothiomorpholin-4-yl)pentyl)phthalimide (1.0g, 97% yield).

Statistics shows that N-(5-Bromopentyl)phthalimide is playing an increasingly important role. we look forward to future research findings about 954-81-4.

Reference:
Patent; Shenzen Chipscreen Biosciences Ltd.; Lu, Xianping; Liu, Jindi; Yang, Qianjiao; Li, Zhiping; Pan, Desi; Shan, Song; Zhu, Jiangfei; Wang, Xianghui; Liu, Xiangheng; Ning, Zhiqiang; (30 pag.)CN105481778; (2016); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 675109-26-9,Some common heterocyclic compound, 675109-26-9, name is 6-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.

6-Bromoisoindolin-l-one (CAS 675109-26-9) (1.61 g, 7.58 mmol, 1.05 equiv.) was suspended in 32 ml of THF and cooled to 0-5C. Sodium hydride (60% dispersion in mineral oil) (318 mg, 7.94 mmol, 1.1 equiv.) was added at 0-5C. The reaction mixture was stirred at room temperature for 15 minutes and then cooled to 0-5C. Methyl (2RS)-2-bromo-2-(5-fluoro-2- methoxyphenyl)acetate (CAS 1368458-30-3) (2.00 g, 7.22 mmol) dissolved in 8.0 ml of THF was added dropwise at 0-5C. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated NH4CI- solution and extracted with ethyl acetate. The aqueous layer was backextracted with ethyl acetate. The organic layers were washed with water and brine. The organic layers were combined, dried over sodium sulfate, filtered and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with an ethyl acetate:heptane 0: 100 to 50:0 gradient to obtain the desired methyl (2RS)-2-(6-bromo-l-oxo- isoindolin-2-yl)-2-(5-fluoro-2-methoxy-phenyl)acetate (2.202 g, 75 % yield) as a yellow foam, MS: m/e = 408.0/410.0 (M+H+).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Bromoisoindolin-1-one, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; C4 THERAPEUTICS, INC.; JAESCHKE, Georg; RICCI, Antonio; RUEHER, Daniel; STEINER, Sandra; DUPLESSIS, Martin; NAGEL, Yvonne Alice; KUHN, Bernd; (60 pag.)WO2018/220149; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem