M.W:200-300 | Page 86 of 87 | Heterocyclic Building Blocks-Benzisoxazole

A new synthetic route of 719-64-2

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,719-64-2,5-Chloro-3-phenylbenzo[c]isoxazole,its application will become more common.

A common heterocyclic compound, 719-64-2,5-Chloro-3-phenylbenzo[c]isoxazole, 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. 719-64-2

(2) Take 10.0g of intermediate (II) into a three-necked bottle.50ml ethanol, 4.8g iron powder,After refluxing for 0.5 h, 1 ml of sulfuric acid (6 mol/L) was added dropwise.After the completion of the dropwise addition, the reaction was refluxed for 1 h.After the reaction is completed, a NaOH solution is added to adjust the pH to 8,Cool down to 50 C, add 0.2g activated carbon,Reflux for 0.5h,Thermal filtration into the crystallization bottle, cooling and crystallization,Ethanol washing, drying to obtain intermediate (III) 9.60g, The yield is 95.1%.The melting point is 96.3-98.2 C.

Reference£º
Patent; Qilu Tianhe Huishi Pharmaceutical Co., Ltd.; Yuwen Li; Guan Qinghua; Zhao Xudong; Li Baoyong; (6 pag.)CN108250091; (2018); A;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

The origin of a common compound about 651780-27-7

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,its application will become more common.

A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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. 651780-27-7

A mixture of ethyl 6-bromobenzoisoxazole-3-carboxylate (550 mg, 1.39 mmol), o- tolylboronic acid (377 mg, 1.5 [EQ),] Pd (PPh3) 4 (171 mg, 0.08 [EQ),] toluene (10 mL), ethanol (1.5 mL), and 1 M [NA2C03] (1.5 [ML)] is stirred at reflux for 3.5 h. The reaction mixture is diluted with [CHUCK] (0.1 L) and [H2O] (0.1 mL). The [CHZC12] solution is dried [(NA2S04),] filtered, and evaporated. The residue is purified by silica chromatography (heptane/EtOAc) to give Preparation [PA.’H] NMR (300 MHz, CDC) 8 8.14 (1H), 7.61 (2H), 7.42 (1H), 7.35-7. 2 (1H), 4.59 (2H), 2.28 (3H), 1.51 (3H).

Reference£º
Patent; PHARMACIA & UPJOHN COMPANY; WO2004/18428; (2004); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

Some scientific research about Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate

651780-27-7 A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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.

Step 3 6-(4-Hvdroxy-2-methyl-phenyl’)-benzordlisoxazole-3-carboxylic acid ethyl esterA solution of 3-methyl-4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenol (0.624 g, 2.67 mmol) and 6-bromo-benzo[d]isoxazole-3-carboxylic acid ethyl ester (0.360 g, 1.33 mmol) in 1,4-dioxane (20 mL) is added to a flask. The flask is evacuated and re-filled with N2 3 times. To this solution, Pd2(dba)3 (0.010 g), tricyclohexyl phosphine (10 mg), and aqueous K3PO4 (1.5 mL, 1.30 M) are added. The resulting mixture is heated to 50 C for 2 hours under N2. The reaction mixture is cooled to room temperature and filtered through a pad of diatomaceous earth. The filtrate is concentrated under reduced pressure. The residue is purified via silica gel chromatography eluting with 25% ethyl acetate in hexanes to give the title compound (0.366 g, 93%). ES/MS m/e 298.0 (M+l); 296.0 (M-I).

Reference£º
Patent; ELI LILLY AND COMPANY; WO2007/92751; (2007); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

Some scientific research about 3-(Bromomethyl)benzo[d]isoxazole

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,37924-85-9,3-(Bromomethyl)benzo[d]isoxazole,its application will become more common.

37924-85-9 A common heterocyclic compound, 37924-85-9,3-(Bromomethyl)benzo[d]isoxazole, 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.

BIOS-Na (Compound III) was prepared in accordance with the method described in Example 1 of U.S. Pat. No. 4,172,896. A solution of sodium sulfite (24.3 grams) in water (390 ml) was added to a solution of 3-bromomethyl-1,2-benzisoxazole (24 grams, Compound II) in methanol (390 ml), stirred with heating to 50 C. for 4 hours. After completion of the reaction, the solution was concentrated under reduced pressure. The resulting crystalline residue was heated to about 50-60 C. in methanol (750 ml) and the solution filtered. The clear filtrate was concentrated under reduced pressure and the resulting crystalline residue was washed with diethyl ether to give crystalline sodium 1,2-benzisoxazole-3-methanesulfonate (18 grams, BIOS-Na, Compound III). Thc thus-produced BIOS-Na was analyzed using X-Ray powder diffraction (results depicted in FIG. 1), differential scanning calorimetry (results depicted in FIG. 2) and thermal gravimetry (results depicted in FIG. 3). The water content of the thus-produced BIOS-Na was 7% as measured by Karl-Fischer titration, indicating that the crystals were of BIOS-Na monohydrate.

Reference£º
Patent; Naddaka, Vladimir; Adin, Itai; Klopfer, Eyal; Arad, Oded; Kaspi, Joseph; US2006/9644; (2006); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

Some scientific research about 651780-27-7

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,651780-27-7,its application will become more common.

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 the bicyclobase according to procedure A. Literature reference: Angell, R. M.; Baldwin, I. R.; Bamborough, P.; Deboeck, N. M.; Longstaff, T.; Swanson, S. W004010995A1 The following acid was prepared using this method: 1,2-Benzisoxazole-3-carboxylic acid., 651780-27-7

Reference£º
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/63767; (2005); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A new synthetic route of Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate

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.

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

A new synthetic route of 3-(Bromomethyl)benzo[d]isoxazole

A common heterocyclic compound, 37924-85-9,3-(Bromomethyl)benzo[d]isoxazole, 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. 37924-85-9

Step 1 : A mixture of tert-butyl methyl((25′)-l-oxo-l-(4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H- spiro[benzo[][l,4]oxazepine-2,4′-pyran]-3-ylamino)propan-2-yl)carbamate (156 mg, 360 muetaiotaomicron), 3-(bromomethyl)benzo[d]isoxazole (83.9 mg, 396 muetaiotaomicron), Cs2C03 (141 mg, 432 muetaiotaomicron) and Nal (64.7 mg, 432 muiotaetaomicron) in DMF (900 mu) was stirred at RT for 18 h, diluted with EtOAc, washed with H20, brine, dried over Na2S04, filtered, and the filtrate concentrated to give a residue that was purified by silica gel chromatography. The resulting material was purified by supercritical fluid chromatography (SFC) to provide tert-butyl (5)-l-((5)-5-(benzo[ ]isoxazol-3-ylmethyl)-4- oxo-2′,3^4,5,5^6′-hexahydro-3H-spiro|enzo[][l,4]oxazepine-2,4′-pyran]-3-ylamino)-l- oxopropan-2-yl(methyl)carbamate (54.5 mg, 27 %) as a white foam.

Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DONNELL, Andrew F.; HAN, Xiaochun; KESTER, Robert Francis; KONG, Norman; LE, Kang; LOU, Yan; MICHOUD, Christophe; MOLITERNI, John Anthony; REMISZEWSKI, Stacy; RUPERT, Kenneth Carey; YUN, Weiya; WO2014/23708; (2014); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

The origin of a common compound about 719-64-2

(3) 5-Chloro-3-phenyl-2,1 benzisoxazole,Iron powder,The concentration of 95% ethanol,Heat reflux at 35C for 30 minutes,Then, ethanol was added dropwise to the system.among them,The volume ratio of hydrochloric acid to ethanol is 1:5.After refluxing, reflux at 35C for 2 hours.Sodium hydroxide solution was added dropwise to adjust the pH of the system to 7,Add activated carbon to the systemContinue refluxing for 20 minutes,filter,The filter residue is vacuum dried at 50C for 4 hours.among them,5-chloro-3-phenyl-2,1benzoxazole,Iron powder,95% ethanol,Ethanol solution of hydrochloric acid,The mass ratio of activated carbon is 2:1.2:15:2:0.2,That is, 2-amino-5-chlorobenzophenone is obtained.

Reference£º
Patent; Shanxi Jujiehan Chemical Co., Ltd.; Li Changying; (5 pag.)CN107698454; (2018); A;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

The origin of a common compound about 3-(Bromomethyl)benzo[d]isoxazole

General procedure: To NaOMe (25% soln, 0.5 mL, 2.2 mmol) in MeOH (5 mL) was added thiosemicarbazide 9 (200 mg, 2.2 mmol). Diethyloxalate (0.3 mL, 2.2 mmol) was then added dropwise. The mixture was heated at 65 C for 2 h and then cooled to rt. 1-(Bromomethyl)-4-chlorobenzene (500 mg, 2.4 mmol) was added in one portion; stirring was continued at rt for 3 h and then heated overnight at 50 C. The reaction mixture was concentrated. The residue was dissolved in EtOAc (40 mL), washed with water (20 mL), and brine (20 mL). The organic phase was dried over Na2SO4, concentrated and purified by silica gel column chromatography (EtOAc w/ 0.2% HOAc). The product was triturated in Et2O to afford 59 mg of 6g as a light yellow solid (10% yield)

Reference£º
Article; Hin, Niyada; Duvall, Bridget; Berry, James F.; Ferraris, Dana V.; Rais, Rana; Alt, Jesse; Rojas, Camilo; Slusher, Barbara S.; Tsukamoto, Takashi; Bioorganic and Medicinal Chemistry Letters; vol. 26; 8; (2016); p. 2088 – 2091;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

Some scientific research about 5-Chloro-3-phenylbenzo[c]isoxazole

719-64-2 A common heterocyclic compound, 719-64-2,5-Chloro-3-phenylbenzo[c]isoxazole, 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.

That is, using the above conditions, Aldimine 1a (54.7mg, 0.2mmol, 100mol%),[RhCp * Cl2] 2 (3.1mg, 0.005mmol, 2.5mol%), AgSbF6 (6.9mg, 0.02mmol, 10mol%),Then in an oven dried and sealed tube filled with PivOH (10.2mg, 0.1mmol, 50mol%),Under room temperature and air, anthranyl 2a (68.9 mg, 0.3 mmol, 200 mol%) and DMF (1 mL) were added.The reaction mixture was stirred at 120 C. for 6 hours and cooled to room temperature.The reaction mixture was diluted with EtOAc (3 mL) and concentrated in vacuo.The residue was purified by flash column chromatography (n-hexane / EtOAc = 7: 1) to give 3a (48.2 mg) in 73% yield.

Reference£º
Patent; SUNGKYUNKWAN University Research & Business Foundation; Kim In-su; Kim Hyeong-sik; (41 pag.)KR2020/25255; (2020); A;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics