Month: March 2021

Electric Literature of 141452-01-9,Some common heterocyclic compound, 141452-01-9, name is Methyl indoline-5-carboxylate, molecular formula is C10H11NO2, 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.

Preparation of Compound 29, 1-tert-butyl 5-methyl indoline-1,5-dicarboxylate[0044] Di-tert-butyl dicarbonate (0.489 g, 2.24 mmol), followed by triethylamine (0.315 mL, 2.24 mmol) was added to a solution of Compound 28 (0.328 g, 1 .85 mmol) in dry DCM (5.8 mL) and the reaction mixture was stirred at rt for 26 hrs, concentrated. The residue was dissolved in EtOAc and washed with water (1 x), brine (1 x), dried (MgS04), filtered and concentrated. The crude material was recrystallized from hot EtOH to afford the title compound (373 mg, 73%) as a white solid. 1H NMR (500 MHz, CDCI3) delta 7.88 (d, J = 7.6 Hz, 1 H), 7.82-7.79 (m, 1 H), 4.02 (t, J = 8.7 Hz, 2H), 3.88 (s, 3H), 3.14 – 3.09 (m, 2H), 1 .57 (br s, 9H). Note that there also appears to be 2 extremely broad and weak singlets centred at 7.85 and 7.50 ppm which may be the missing aromatic CH. LRMS (ESI+): 178.09 (loss of Boc) and very weak 278.15

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

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; JONES, Keith; RYE, Carl; CHESSUM, Nicola; CHEESEMAN, Matthew; PASQUA, Adele Elisa; PIKE, Kurt Gordon; FAULDER, Paul Frank; WO2015/49535; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 22190-33-6, 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. 22190-33-6, name is 5-Bromoindoline belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A solution of the title A compound, 5-bromo-2, 3-DIHYDRO-1 H-INDOLE (15. 75 g, 79.54 mmol) in 200 mL acetonitrile and 200 mL dichloromethane is treated with DMAP (0.971 g, 7.95 mmol) and di-t-butyl dicarbonate (19.14 g, 87.49 MMOL). The solution is stirred at RT for 16 h. The mixture is diluted with 300 mL dichloromethane and washed twice with 1 N aqueous HCI and once with brine, dried over anhydrous MGS04, and concentrated to afford 5-bromo-2,3- dihydro-indole-1-carboxylic acid tert-butyl ester.

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-Bromoindoline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2004/65351; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 3891-07-4,Some common heterocyclic compound, 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, molecular formula is C10H9NO3, 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, 2400 ml of tetrahydrofuran was charged into the reaction flask A, and the mixture was cooled to -10 C or less, 750 g of N-hydroxyethyl phthalimide and 345 g of NaH were added successively (while stirring at a low speed, N-hydroxyethyl phthalimide, NaH added to the beginning of the dropwise addition of ethyl 4-chloroacetoacetate time interval within 30min); the reaction flask temperature down to -10 C below, 732 g of ethyl 4-chloroacetoacetate was added slowly dropwise, and the temperature was controlled below 0 C and the addition was completed in 1.5 to 2 hours. The temperature was raised to 28 to 32 C. After 5 to 6 hours of reaction, 1500 ml of toluene was added, The temperature dropped below 5 C to give a toluene dilution of the reaction solution; b, add 1700 ml of toluene, 2800 ml of water and 1178 g of acetic acid to the reaction flask B at a temperature below 5 C; add the toluene dilution of the above reaction solution with 1 to 1.5 h at a temperature below 10 C; After stirring for 10 min, the mixture was allowed to stand for 15 min, and the aqueous layer was removed. The toluene layer was washed 5 times with a mass fraction of 4% brine (2500 ml each). After the washed toluene solution was added anhydrous magnesium sulfate, And the toluene solution was concentrated under reduced pressure to remove toluene (the amount of toluene removed was 2700 ml or more and the toluene content was not more than a predetermined value) to give ethyl-4- (2-phthalimidoethoxy) acetoacetate in a yield of 93%

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

Reference:
Patent; Qianhui Pharmaceutical (Anhui) Co., Ltd.; Yang Huilai; Mao Jie; Sun Xuexi; (7 pag.)CN106749187; (2017); A;,
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Electric Literature of 552330-86-6, 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. 552330-86-6, name is 5-Bromoisoindolin-1-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Step B: 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)isoindolin-l-one [0231] 5-Bromoisoindolin-l-one (0.066 g, 0.311 mmol), bis(pinacolato)diboron (0.119 g, 0.467 mmol), potassium acetate (0.092 g, 0.934 mmol), and PdCl2(dppf)CH2Cl2 adduct (0.013 g, 0.016 mmol) were suspended in DMA (0.6 mL), degassed with N2, and stirred in a sand bath at 100C overnight. The reaction mixture was subsequently cooled, diluted with EtOAc (10 mL), and passed through a syringe filter. The filtrate was diluted with water (10 mL) and the layers were separated. The aqueous layer was washed with EtOAc (2 x 5 mL). The organic layers were combined and concentrated in vacuo to give the title compound as brown oil, which was used without further purification.

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-Bromoisoindolin-1-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; LAWSON, John David; SABAT, Mark; SMITH, Christopher; WANG, Haixia; CHEN, Young K.; KANOUNI, Toufike; WO2013/148603; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 59-48-3,Some common heterocyclic compound, 59-48-3, name is Indolin-2-one, molecular formula is C8H7NO, 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.

5-Bromo-2-oxindole 2-Oxindole (1.3 g) in 20 mL acetonitrile was cooled to -10 C. and 2.0 g N-bromosuccinimide was slowly added with stirring. The reaction was stirred for 1 hour at -10 C. and 2 hours at 0 C. The precipitate was collected, washed with water and dried to give 1.9 g (90% yield) of the title compound. 2-Oxindole (53.3 g) was suspended in 640 mL acetonitrile and the mixture cooled to 7 C. in an ice bath with mechanical stirring. Solid N-bromosuccinimide (74.8 g) was added in portions over 20 minutes. After about one-third of the N-bromosuccinimide had been added (over 5 minutes), the temperature had increased to 12 C. The addition was halted until the temperature of the mixture had dropped to 10 C. The addition was resumed keeping the temperature below 12 C. After the addition was complete, the mixture was stirred for 1 hour at 10 C. and then for 1 additional hour during which the mixture was allowed to warm to ambient temperature. The precipitate was collected by vacuum filtration, washed with 80 mL of ethanol and sucked dry for 20 minutes in the filtration funnel to give product containing 6.4% of 2-oxindole by HPLC. The solid was suspended in 1440 mL of denatured ethanol and slurry-washed by stirring and refluxing for 5 minutes at which time most of the solid had dissolved. The mixture was cooled in an ice bath to 13 C. The solid product was collected by vacuum filtration, washed with 80 mL of ethanol and dried under vacuum to give 57.7 g (68.0%) of 5-bromo-2-oxindole containing 1.13% 2-oxindole by HPLC. Slurry-washing with 30% less ethanol gave a better yield (88%) but contained more 2-oxindole (1.76%).

The synthetic route of 59-48-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sugen, Inc.; US6878733; (2005); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 5181-35-1, name is 2-(2-Bromoethoxy)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. category: indolines-derivatives

To a solution of 2-(2-bromoethoxy) isoindoline-l,3-dione (10 g, 37 mmol) and tert-buty 2-(lH-tetrazol-5-yl)ethylcarbamate (7.88 g, 37 mmol) in dimethyl formamide (50 ml) was added cesium carbonate ((14.48 g, 44 mmole) in portion wise at 25-30 C under stirring. The reaction mixture was stirred for further 16 hours and filtered; the filtrate was slowly poured into chilled water (400 ml) under stirring and continued stirring for 30 minutes. The formed precipitates of compound were filtered and washed with water (40 ml). The solid compound was dried at 40C for 2 hour under high vacuum, yielded 12 g. The compound was column purified using hexane and acetone as an eluent. The mixture was isolated at 10-15% concentration of acetone in hexane to yield 10 g of 2-{2-[5-(2-tertiary butoxy carbonyl aminoethyl)-2H-tetrazol-2-yl]ethoxy}-lH-isoindole-l,3(2H)-dione and 2-{2-[5-(2-tertiary butoxy carbonyl aminoethyl)-lH-tetrazol-l-yl]ethoxy}-lH-isoindole-l,3(2H)-dione in 67% yield Analysis: Mass: 403 (M+l); for Molecular weight: 402 and Molecular formula: C18H22N6O5..; Hydrazine hydrate monohydrate (1.86 ml, 037.3 mmol) was added to a solution of 2-{2-[5-(2- tertiary-butoxy-carbonyl-aminoethyl)-2H-tetrazol-2-yl]ethoxy}-lH-isoindole-l,3(2H)-dione and 2- {2-[5-(2-tertiary-butoxy-carbonyl-aminoethyl)-lH-tetrazol-l-yl]ethoxy}-lH-isoindole-l,3(2H)- dione (10 g, 24.8 mmol, obtained from step 1) in dichloromethane (10 ml) under stirring at room temperature. After completion of 2 hours of stirring at same temperature the TLC confirms the completion of reaction. The reaction mass was filtered and the solid was washed with dichloromethane (50 ml). The collected filtrate was concentrated at 40C under vacuum to yield 6.75 g of the product, which was used further without any purification. Analysis: Mass: 273 (M+l); for Molecular weight: 272 and Molecular formula: CioH2oN603; To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-l,6- diaza-bicyclo[3.2.1]octane-2-carboxylic acid (6.2 g, 22 mmol) in dimethylformamide (50 ml) was added EDC.HC1 (6.45 g, 33.6 mmol) at ambient temperature under stirring. To this was added N- methyl morpholine (7.23 ml, 67.3 mmol) followed by HOBT (3.04 g, 22 mmol) under stirring and reaction mixture was stirred for 5 minutes and cooled to 15C and a solution of mixture of tert- butyl (2-{ l-[2-(aminooxy)ethyl]-lH-tetrazol-5-yl}ethyl)carbamate and tert-buty (2-{2-[2- (aminooxy)ethyl]-2H-tetrazol-5-yl}ethyl)carbamate (6.72 g, 24.7 mmol) in dimethylformamide (12 ml) was slowly added and allowed to reach ambient temperature and stirred for 16 hours. The progress of reaction was monitored by TLC, after complete conversion of starting material the reaction mixture was slowly poured onto chilled water (500 ml) and extracted with ethyl acetate (2×150 ml). The combined organic layer was washed with brine (75 ml) and organic layer was dried over anhydrous sodium sulfate. The organic layer was concentrated on rotavapour to provide 4.2 g of crude compound. The crude compound was column purified by using hexane and acetone as an eluent. The non-polar spot isolated at 10-15% concentration of acetone in hexane yielded 1.6 g of (2S,5R)-N-{2-[5-(2-tertiary butoxy carbonyl aminoethyl)-2H-tetrazol-2-yl]ethoxy}-6- benzyloxy-7-oxo-l,6-diazabicyclo[3.2.1]octane-2-carboxamide. The polar spot isolated at 20-25% concentration of acetone in hexane and the pure fractions were collected and concentrated on Rota evaporator to yield 1.4 g of (2S,5R)-N-{2-[5-(2-tertiary butoxy carbonylaminoethyl)-lH-tetrazol-l- yl]ethoxy}-6-benzyloxy-7-oxo-l,6-diazabicyclo[3.2.1] octane-2-carboxamide as white compound, in 25% yield. Analysis: Mass: 531 (M+l); for Molecular weight: 530 and Molecular formula: C24H34N8O6. 1H NMR (DMSO-de): delta 9.30 (s, 1H), 7.43-7.33 (m, 5H), 5.05-5.02 (m, 1H), 4.90-4.83 (m, 3H), 4.47-4.43 (m, 2H), 3.92-3.91 (d, 1H, J= 7.2 Hz), 3.59-3.57 (m, 2H), 3.30 (s, 1H), 3.11-3.08 (m, 2H), 2.99-2.97(m, 1H), 2.71-2.68 (m, 1H), 2.29-2.24 (m, 2H),m 2.04-1.89 (m, 3H), 1.49 (s, 9H).

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

Reference:
Patent; WOCKHARDT LIMITED; TADIPARTHI, Ravikumar; PATIL, Vijaykumar Jagdishwar; DEKHANE, Deepak; SHAIKH, Mohammad Usman; BIRAJDAR, Satish; DOND, Bharat; PATEL, Mahesh Vithalbhai; (100 pag.)WO2017/81615; (2017); 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 7699-18-5 as follows. Recommanded Product: 7699-18-5

General procedure: To a Schlenk tube were added oxindole 1 (0.3 mmol), t-BuONO (0.6 mmol), andTHF (2 mL). Then the tube was stirred at 50 C under 1 atm of O2 for the indicatedtime until complete consumption of starting material monitored by TLC analysis.After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with ethyl acetate. The combined organic extractswere dried over Na2SO4, removal of the solvent under vacuum afforded the crudeproduct, which was purified further by column chromatography using hexane-ethylacetate.

According to the analysis of related databases, 7699-18-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Wei, Wen-Ting; Ying, Wei-Wei; Zhu, Wen-Ming; Wu, Yi; Huang, Yi-Ling; Cao, Yi-Qi; Wang, Yi-Ning; Liang, Hongze; Synlett; vol. 28; 17; (2017); p. 2307 – 2310;,
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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. 1035235-27-8, name is tert-Butyl 4-bromoisoindoline-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C13H16BrNO2

A mixture of tert-butyl 4-bromoisoindoline-2-carboxylate (1.70 g, 5.70 mmol),4,4,4?,4?,5 ,5 ,5 ?,S ?-octamethyl-2,2?-bi(1 ,3 ,2-dioxaborolane) (1.74 g, 6.84 mmol), potassiumacetate (1.68 g, 17.1 mmol), and PdC12(dppf) DCM adduct (0.466 g, 0.570 mmol) in 1,4-dioxane (25 mL) was bubbled with nitrogen and stirred at 80 C overnight. The mixture was cooled to room temperature, diluted with EtOAc, washed with water, dried and concentrated. The residue was subjected to colunm chromatography on silica gel, eluting with EtOAc-hexanes (gradient from 0-30%), to provide tert-butyl 4-(4,4,5 ,5 -tetramethyl5 1 ,3,2-dioxaborolan-2-yl)isoindoline-2-carboxylate as a white solid (1.50 g, 76% yield).

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 1035235-27-8.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; AHMAD, Saleem; BATT, Douglas G.; LIU, Qingjie; MACOR, John E.; TINO, Joseph A.; WATTERSON, Scott Hunter; NAIR, Satheesh Kesavan; MAISHAL, Tarun Kumar; (247 pag.)WO2016/65236; (2016); A1;,
Indoline – Wikipedia,
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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. 435273-55-5, name is 4-Bromo-2-methylisoindolin-1-one, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 435273-55-5

To a mixed solution of compound 3b (5 g, 22 mmol), bisboronic acid pinacol (8.5 g, 33 mmol) and KOAc (3.2g, 33 mmol) in 1,4-dioxane (50 ml) was added Pd(dppf)2Cl2 (1g), and flushed with nitrogen. The reaction flask wassealed and the reaction was stirred overnight at 85C. After cooled to room temperature, an aqueous Na2CO3 solution (2.5M, 10ml), Pd(dppf)2Cl2 (1g) and 2,5-dibromo-3-nitropyridine (9 g, 33 mmol) were added. After flushed with nitrogenfor 10 minutes, the reaction flask was sealed and the mixture was stirred overnight at 85C. The reaction was pouredinto water and extracted with ethyl acetate. The organic phase mixture was dried over Na2SO4, dried by suction andpurified by silica gel column chromatography (PE:EA=10:2 to 1:1) to provide compound 3c as a yellow solid.MS(ESI)m/z:347.9(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 435273-55-5.

Reference:
Patent; NINGBO WENDA PHARMA TECHNOLOGY LTD.; WANG, Nenghui; (65 pag.)EP3406612; (2018); A1;,
Indoline – Wikipedia,
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Related Products of 16800-68-3, A common heterocyclic compound, 16800-68-3, name is 1-Acetylindolin-3-one, molecular formula is C10H9NO2, 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.

The pent -2 -acetylenic acid 4 – nitrophenyl-unit 65.7 mg (0.3 mmol), was used. N- Acetylindole -3 -unitz 26.3 mg (0.15 mmol), the carbene-unitz (0.015 mmol), 3.96 mg, 1 diazabicycloundecene 8 – (-7 -) and methylene-methylene chloride shown in Formula 45 mul IV 0.3 mmol were placed in 3 ml a 25 ml unitunito-two-port 3h bottle, and reacted 30 C, under unituniteous conditions, and concentrated, under inert atmosphere protection, unitant-like conditions. The eluate fractions of all the products 10:1 detected were collected by chromatography with petroleum ether: ethyl acetate in the timetime as eluent column chromatography, and the solvent was evaporated to obtain the residue unit, 27 mg and gave rise 72% to unit_.

The synthetic route of 16800-68-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; China Pharmaceutical University; Du Ding; Sun Kewen; (10 pag.)CN110156800; (2019); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem