Category: Benzisoxazole

36216-80-5,A common heterocyclic compound, 36216-80-5,Benzo[d]isoxazol-3-amine, 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 prepare a-5, a-4 (2.1 g, 0.015 mol) was added to chlorosulfonic acid (4.1 ml, 0.060 mol) at room temperature (RT). Said reaction mixture was stirred overnight under an inert atmosphere such as nitrogen at 60C. The mixture was then poured in ice/water. The precipitate was filtered and dried with toluene in a Buchi-apparatus (2.1 g, yield 60%).

The chemical industry reduces the impact on the environment during synthesis, 36216-80-5,Benzo[d]isoxazol-3-amine,I believe this compound will play a more active role in future production and life.

Reference£º
Patent; TIBOTEC PHARMACEUTICALS LTD; WO2003/97616; (2003); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

16263-54-0, 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.16263-54-0,3,6-Dichlorobenzo[d]isoxazole, it is a common compound, a new synthetic route is introduced below.

(a) 3-(1-Piperazinyl)-6-chloro-1,2-benzisoxazole. A mixture of 3,6-dichloro-1,2-benzisoxazole and piperazine is reacted according to the procedure of Example 2. The 3-(1-piperazinyl)-6-chloro-1,2-benzisoxazole intermediate is isolated in 79% yield and 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. 16263-54-0, other downstream synthetic routes, hurry up and to see.

Reference£º
Patent; Mead Johnson & Company; US4411901; (1983); A;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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. 5-Methylbenzo[d]isoxazol-3-amine,89976-56-7, This compound has unique chemical properties. The synthetic route is as follows.,89976-56-7

The crude 5-methyl-benzo[d]isoxazol-3-ylamine was dissolved in 60 mL CH2Cl2. To this solution was added di-tert-butyl-dicarbonate (14.6 g, 66.8 mmol) and a catalytic amount of DMAP. The reaction mixture was stirred at RT overnight. The mixture was concentrated in vacuo to about 30 mL volume, treated with hexanes and filtered to yield 4.8 g of N,N-di-Boc-5-methyl-benzo[d]isoxazol-3-ylamine as a solid.

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 89976-56-7.

Reference£º
Patent; Bolin, David Robert; Hamilton, Matthew Michael; McDermott, Lee Apostle; Qian, Yimin; US2011/112158; (2011); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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 651780-27-7,651780-27-7

651780-27-7, 20a) Ethyl 6-(4-hydroxyphenyl)-l,2-benzisoxazole-3-carboxylateEthyl 6-bromo-l,2-benzisoxazole-3-carboxylate (0.34 g, 1.26 mmol), (4- hydroxyphenyl)boronic acid (0.21, 1.51 mmol), tetrakis(triphenylphosphine)palladium (0) (0.06 g, 0.05 mmol) and 2 M sodium carbonate (5 mL) in 1 ,2-dimethoxyethane (6 mL) were stirred at 80 0C for 1 hour. The reaction mixture was diluted with water, followed by ethyl acetate. The layers were separated and the ethyl acetate layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated to afford the crude material. The crude material was purified using hexanes: ethyl acetate (0 to 40% ethyl acetate) to afford a mixture of desired product, plus the free acid of the desired product, 6-(4-hydroxyphenyl)-l,2- benzisoxazole-3-carboxylic acid. All the fractions were combined and concentrated.

According to the analysis of related databases, 651780-27-7, the application of this compound in the production field has become more and more popular.

Reference£º
Patent; SMITHKLINE BEECHAM CORPORATION; WO2008/157270; (2008); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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. 36216-80-5,Benzo[d]isoxazol-3-amine, 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.36216-80-5

Example 148: N-(benzo[d]isoxazol-3-yl)-2,4-dimethoxybenzenesulfonamide 148 A solution of 2,4-dimethoxybenzenesulfonyl chloride (0.18 g, 0.75 mmol) and benzo[d]isoxazol-3-amine (0.10 g, 0.75 mmol) in pyridine (1 ml.) was irradiated in the microwave at 1 10 C for 2 hours. The resultant mixture was loaded onto silica gel and the product purified twice by column chromatography (4 g Si02 cartridge, 0-45% EtOAc in petroleum benzine 40-60 C then 4g Si02 cartridge, 0-35% EtOAc in petroleum benzine 40-60 C) to yield two batches (78 mg and 5 mg) of [183] the title compound (total mass 83 mg, 33 % yield) as white solids. 1H NMR (400 MHz, CDCI3) d 8.1 1 (d, J = 8.05 Hz, 1H), 7.79 (s, 1H), 7.70 (d, J = 8.81Hz, 1H), 7.57 – 7.50 (m, 1H), 7.47 – 7.40 (m, 1H), 7.37 – 7.29 (m, 1H), 6.50 (d, J = 2.27 Hz, 1H), 6.42 (dd, J = 2.25, 8.81Hz, 1H), 3.98 (s, 3H), 3.81 (s, 3H). LCMS-B: rt 3.20 min, m/z = 356.8 [M+Na]+, 334.8 [M+H]+., 36216-80-5

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. Benzo[d]isoxazol-3-amine, We look forward to the emergence of more reaction modes in the future.

Reference£º
Patent; CTXT PTY LIMITED; STUPPLE, Paul, Anthony; LAGIAKOS, Helen, Rachel; MORROW, Benjamin, Joseph; FOITZIK, Richard, Charles; HEMLEY, Catherine, Fae; CAMERINO, Michelle, Ang; BOZIKIS, Ylva, Elisabet, Bergman; WALKER, Scott, Raymond; (321 pag.)WO2019/243491; (2019); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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. 719-64-2,5-Chloro-3-phenylbenzo[c]isoxazole, 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.719-64-2

719-64-2, The preparation method is as follows: 5-chloro-3-phenyl 2,1-benzisoxazole (commercially available) (0.3 mmol, 68.7 mg), phenylacetaldehyde (0.6 mmol, 72.0 mg), copper powder (0.06) Methanol, 3.8 mg) and silver triflate (0.03 mmol, 8.0 mg) were added to a 25 ml Schlenk tube, and the reaction tube was replaced with oxygen three times under reduced pressure.Hexafluoroisopropanol (2 ml) was added and stirred at 110 C for 30 hours.After completion of the reaction, a column chromatography of silica gel of 100-200 mesh was added, and the solvent was evaporated under reduced pressure. The crude product was subjected to silica gel column chromatography, eluting with petroleum ether and ethyl acetate ( petroleum ether: ethyl acetate = 20:1) The liquid was eluted, and the elution was carried out by TLC elution. The eluate containing the desired product was collected, and the desired product eluent was combined and evaporated to give the quinoline compound of the formula i above, yield 69%. This material is a red solid.

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, 5-Chloro-3-phenylbenzo[c]isoxazole.

Reference£º
Patent; Jiangnan University; Zou Lianghua; Zhu Hao; Zhu Shuai; Li Pinggui; Yan Cheng; (12 pag.)CN110204486; (2019); A;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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 239097-74-6,Benzo[d]isoxazol-5-amine, as follows.239097-74-6

To a suspension of intermediate ester (105 mg, 0.340 mmol) in DMF (0.5 mL) was added a solution of 1,2-benoxazol-5-amine (46 mg, 0.340 mmol) in DMF (0.5 mL). The reaction mixture was stirred at room temperature for 2 hours until the reaction was complete, and quenched with the addition of TFA (5 drops). The precipitated solid was collected by filtration, suspended in DCM, basified with saturated NaHCO3 to pH ~8. The aqueous layer was extracted with DCM, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by trituration in DCM/Et2O, collected by filtration, and dried in vacuo to give the title compound (50 mg, 48%) as a yellow solid.1H NMR (400 MHz, CDCl3): delta 10.05 (s, 1H), 8.72 (s, 1H), 8.55 (s, 1H), 8.07 (s, 1H), 7.68 (dd, J = 6.8 Hz, 1.6 Hz, 1H), 7.59 (d, J = 6.8 Hz, 1H), 6.59 (s, 1H), 2.71 (s, 3H), 2.70 (s, 3H). LC-MS m/z: 308.1 [M+H+]. HPLC Purity (214 nm): 98%; tR = 8.38 min.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Benzo[d]isoxazol-5-amine, and friends who are interested can also refer to it.

Reference£º
Patent; LYSOSOMAL THERAPEUTICS INC.; SKERLJ, Renato, T.; LANSBURY, Peter, T.; GOOD, Andrew, C.; BOURQUE, Elyse Marie, Josee; (134 pag.)WO2016/73889; (2016); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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 851768-35-9,5-Amino-3-methylbenzo[d]isoxazole, as follows.851768-35-9

851768-35-9, Synthesis of 2, 5-dichloro-N- (3-methvl-benzofdlisozazol-5-vl)- benzenesulfonamide, STX 876 (KRB01030) :; To a solution of 2, 5-dichlorobenzenesulphonyl chloride (105 mg, 0.428 mmol) in dichloromethane (3 mL) was added pyridine (100 pL, 1.02 mmol) and the mixture was stirred under N2 for 5 min, after which time 5-amino-3-methyl-1, 2-benzisoxazole (60 mg, 0.41 mmol) was added. The resulting mixture was stirred for 2 h at room temperature, then saturated NaHCO3 solution (8 mL) was added and the mixture was extracted into ethyl acetate (15 mL). The organic phase was washed with brine, dried (Na2SO4), filtered and evaporated to give a residue that was purified using flash chromatography to afford a yellow solid (100 mg, 68%), single spot at Rf 0.62 (1: 1 hexane: ethyl acetate). mp 229.4-230. 0C, HPLC purity 94% (tR 2.18 min in 10% water-acetonitrile).’H NMR (CDC13) : 6 7.89 (1H, d, J=2.2 Hz), 7.43 (4H, m), 7.22 (1H, m), 7.09 (1H, s, N-H), 2.54 (3H, s). LCMS: 340.06 (M-CH3). FAB-MS (MH+, C14H10CI2N203S) : calcd 356.9867, found 356.9860

According to the analysis of related databases, 5-Amino-3-methylbenzo[d]isoxazole, the application of this compound in the production field has become more and more popular.

Reference£º
Patent; STERIX LIMITED; WO2005/42513; (2005); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, as follows.651780-27-7

Diethyl malonate (12.6 g, 79 mmol) was added to a suspension of sodium hydride (3.16 g, 132 mmol) in dimethylsulfoxide (60 ml) over 30 min. The temperature of the reaction rose to 60 C and the mixture clarified. 1,4-Dibromo-2-nitrobenzene (10 g, 36.0 mmol) was added and the solution was maintained for 2 h at 100 C. The reaction mixture was allowed to cool to rt and was poured into ice (300g-400g). The precipitated solids were isolated by filtration and dried to provide 11.0 g of the product (89%). The ester (11.0 g, 32.0 mmol) was diluted with a 2 N solution of sodium hydroxide (32 mL, 63 mmol) and the reaction mixture was maintained at room temperature for 16 h. The aqueous layer was extracted with dichloromethane (20 mL) and was acidified. The precipitated solids were isolated by filtration and dried to provide 7.00 g of the acid (89%). Sulfuric acid (1 mL) was added to a solution of the acid (7.00 g, 27.0 mmol) in ethanol (60 ml). The reaction mixture was warmed to reflux, maintained for 2 h, and was concentrated under reduce pressure. The residue was partitioned between ethyl acetate (250 mL) and saturated sodium carbonate (50 mL) and the organic layer was washed with saturated sodium carbonate (50 mL) and brine (50 mL). The organic layer was dried (sodium sulfate) and concentrated to provide 8.00 g (98%) of the ester as a liquid. Under N2 atmosphere, sodium ethylate was formed with sodium (33.5 g, 1.46 mol) in ethanol (1.0 L). Isoamylnitrite (225 mL) was added to a solution of the ester (420 g, 1.46 mol) in ethanol (3 L) in a 10 L three-necked round bottom flask and the mixture was warmed to 60 C. A solution of sodium ethoxide, prepared from sodium metal (33.5 g, 1.46 mmol) in ethanol (1 L) was added dropwise and the reaction mixture was maintained for 2 h. The reaction mixture was allowed to cool to rt and was neutralized with 2 N hydrochloric acid. The reaction mixture was extracted with ethyl acetate (4 x 2L) and the combined organic layers were washed with water (2 x 1 L) and brine (2 x 1 L) and dried (sodium sulfate). The residue was purified by chromatography (1/1 to 0/1 hexane/ethyl acetate) to provide 110 g of the product ( 28%). 10% Palladium on carbon (1.5g) and triethylamine (7.5 g, 82.4 mmol) were added to a solution of ethyl 6-bromobenzisoxazole-3-carboxylate (20g, 0.081mol) in ethanol (300ml) at 0 C under an atmosphere of nitrogen. The nitrogen atmosphere was removed by evacuation and replaced with hydrogen gas, and the reaction mixture was maintained for 1 hour. The hydrogen atmosphere was removed by evacuation and replaced with nitrogen gas, and the palladium removed’by filtration through Celite. The filter cake was washed with ethanol (3 x 50 mL) and the filtrates were concentrated. The residue was- dissolved in dichloromethane (200 mL) and the solution was washed with water (4 x 50 mL), dried (sodium sulfate) and evaporated to provide 13.0 g of the product as a yellow solid (96%). The ester was saponified using sodium hydroxide to provide the acid. The acid was coupled with 1,4-diazabicyclo[3.2.2]nonane according to procedure A.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, and friends who are interested can also refer to it.

Reference£º
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/111038; (2005); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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. Benzo[d]isoxazol-3-amine,36216-80-5, This compound has unique chemical properties. The synthetic route is as follows.,36216-80-5

To a solution of benzo[d]isoxazol-3-amine (1 eq.) and quinuclidin-3-one (1.1 eq.) in toluene (7 mL/mmol benzo[d]isoxazol-3-amine) at 25 C was added portion-wise titanium(IV) isopropoxide (9 eq.). The resulting solution was stirred at 100 C for 12 hours. On completion, the mixture was cooled to 0 C, and ethanol (1 mL/mmol benzo[d]isoxazol-3-amine) was added via syringe, followed by sodium borohydride (3.7 eq.) in portions. The reaction was stirred at 25 C for 3 hours, then quenched with saturated aqueous potassium carbonate solution, resulting in the formation of a solid. The mixture was filtered, and the filtrate was extracted with dichloromethane (5 chi 50 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The filter cake from the original filtration was slurried with methanol, and the mixture was filtered. The filtrate was directly evaporated to dryness. The combined residue from both batches was dissolved in 4N hydrochloric acid (20 mL) and stirred at room temperature for 4 hours. The mixture was made basic by addition of saturated potassium carbonate solution and extracted with dichloromethane (5 x 50 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by prep-HPLC to give the racemic aminobenzoisoxazole product. [00408] Chiral Separation: A solution of racemic aminobenzoisoxazole product in 3-5 mL of methanol was separated by cSFC (Waters SFC Prep 80, Column temperature: 25 C, back pressure: 100 bar, and wavelength: 220 nm). Each set of collected fractions was concentrated at room temperature. The residue was dissolved in 0.2 M hydrochloric acid and lyophilized to give each enantiomer of the aminobenzoisoxazole product; Following general procedure Bl, rac-1 was prepared from benzo[d]isoxazol-3 -amine (0.40 g, 3.0 mmol). The product was purified by prep-HPLC [Instrument: GX-A; Column: Phenomenex Gemini C18 150×25 mm, particle size: 10 mupiiota; Mobile phase: 44-74% acetonitrile in H20 (add 0.5% NH3 H20, v/v)] to give rac-1 (70 mg, 9% yield) as a yellow solid. LCMS (B): tPv=1.179 min., (ES+) m/z (M+H)+ = 244.2.

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 36216-80-5.

Reference£º
Patent; FORUM PHARMACEUTICALS, INC.; ACHARYA, Raksha; BURNETT, Duane, A.; BURSAVICH, Matthew, Gregory; COOK, Andrew, Simon; HARRISON, Bryce, Alden; MCRINER, Andrew, J.; (127 pag.)WO2016/201096; (2016); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics