Day: September 14, 2020

239097-74-6 A common heterocyclic compound, 239097-74-6,Benzo[d]isoxazol-5-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.

Synthesis of N-benzofdlisoxazol-5-vl-2, 5-dichloro-benzenesulfonamide, STX 920 (KRB01048):; To a solution of 2, 5-dichlorobenzenesulphonyl chloride (192 mg, 0.783 mmol) in dichloromethane (4 mL) was added pyridine (150 uL, 1.86 mmol) and the mixture was stirred under N2 for 5 min, after which time 5-amino-1, 2-benzisoxazole (100 mg, 0.746 mmol) was added. The resulting mixture was stirred for 2 h at room temperature, then saturated NaHCO3 solution (10 mL) was added and the mixture was extracted into ethyl acetate (20 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 white solid (174 mg, 68%), single spot at Rf 0.68 (1: 1 hexane: ethyl acetate). mp 172.9- 173. 6C, HPLC purity 99+% (tR 2.41 min in 10% water-acetonitrile).’H NMR (CDCI3) : 5 8.64 (1H, s), 7.89 (1H, d, J=2.2 Hz), 7.56-7. 28 (5H, m). LCMS: 341.07 (M-). FAB-MS (MH+, C13H8Cl2N2O3S) : calcd 342.9711, found 342.9710., 239097-74-6

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Benzo[d]isoxazol-5-amine,239097-74-6,its application will become more common.

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

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: To a -78 C solution of ((S)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[bl[1,4ldiazepin- 3-yl)-carbamic acid tert-butyl ester (807 mg, 2.91 mmol) in THF (19.4 mL) was added lithium bis(trimethylsilyl)amide (3.2 mL, 1.0 M solution in THF, 3.2 mmol), dropwise. The mixture was stirred at -78 C for 15 mm, then a mixture of Nal (523 mg, 3.49 mmol) and 3- (bromomethyl)benzo[dlisoxazole (740 mg, 3.49 mmol) in THF (9.7 mL) was added dropwise over 10 mm. The mixture was stirred at -78 C for 50 mm., warmed to RT and stirred for 4.5 h. The mixture was diluted with 1 N citric acid and extracted with EtOAc. The combined extractswere washed with sat. aq. NaHCO3, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography. The resulting material was repurified by flash chromatography to provide a -4:1 mixture of (S)-tert-butyl 1-(benzo[dlisoxazol-3-ylmethyl)-2- oxo-2,3 ,4,5-tetrahydro- 1 H-benzo [bI [1 ,4jdiazepin-3-ylcarbamate and (S)-tert-butyl 1- (benzo [djisoxazol-3 -ylmethyl)-4-oxo-2,3 ,4,5 -tetrahydro- 1 H-benzo [bI [1,41 diazepin-3-ylcarbamate (742 mg, 63 %) as a yellow foam. LC-MS mlz 431 [M+Naj.Step 1: To a 0C solution of -4:1 mixture of tert-butyl (S)-1-((S)-1-(benzo[djisoxazol-3- ylmethyl)-2-oxo-2,3 ,4,5-tetrahydro- 1 H-benzo [bI [1,41 diazepin-3 -ylamino)- 1 -oxopropan-2- yl(methyl)carbamate and tert-butyl (S)-i -((S)-i -(benzo[dlisoxazol-3-ylmethyl)-4-oxo-2,3 ,4,5- tetrahydro- 1 H-benzo [bI [1 ,4ldiazepin-3-ylamino)- 1 -oxopropan-2-yl(methyl)carbamate (209.4 mg, 424 tmol) in CH2C12 (4.24 mL) was added pyridine (343 tL, 4.24 mmol), followed by methyl 4-(chlorocarbonyl)benzoate (92.7 mg, 467 tmol). After 1 h at 0 C the mixture was diluted with H20 and extracted with CH2C12. The combined extracts were washed with 1 N aq. citric acid, sat. aq. NaHCO3, and brine, dried over Na2504, filtered, and concentrated. The residue was purified by flash chromatography. The resulting material was repurified by flash chromatography to provide methyl 4-((S)-5-(benzo[djisoxazol-3 -ylmethyl)-3 -((S)-2-(tert-butoxycarbonyl(methyl)amino) propanamido)-4-oxo-2,3 ,4,5 -tetrahydro- 1 Hbenzo[b l[1,4ldiazepine-1-carbonyl)benzoate (194 mg, 70 %) as a white solid. LC-MS mlz 678 [M+Naj .

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.

Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; CHEN, Shaoqing; DONNELL, Andrew F.; KESTER, Robert Francis; LE, Kang; LOU, Yan; MICHOUD, Christophe; REMISZEWSKI, Stacy; RUPERT, Kenneth C.; WEISEL, Martin; WO2015/71393; (2015); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A common heterocyclic compound, 16263-54-0,3,6-Dichlorobenzo[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. 16263-54-0

3,6-dichlorobenzisoxazole (5.2 g, 27.8 mmol) and piperazine anhydride (24 g, 278 mmol) were placed in an eggplant type flask and reacted at 120 C. for 24 hours. After completion of the reaction, 52 ml of ice water was added to quench , Add 15 ml of 50% NaOH solution to the solution, stir for 5 minutes, extract with 30 ml * 3 dichloromethane, combine dichloromethane layer, wash with saturated brine 20 ml, dehydrate with anhydrous MgSO 4, evaporate to dryness, Isolated by alumina (200-300 mesh) column chromatography eluting with dichloromethane: methanol = 100: 1 to obtain 4.7 g of 6-chloro-3-piperazinyl-benzisoxazole, Yield is 71%.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,16263-54-0,3,6-Dichlorobenzo[d]isoxazole,its application will become more common.

Reference£º
Patent; JIANGSU HENGYI PHARMACEUTICAL COMPANY LIMITED; SHANGHAI INSTITUTE OF PHARMACEUTICAL INDUSTRY; Li, JIANQI; PENG, SHAOPING; CAI, WANGPING; GAO, KAI; (39 pag.)JP5714152; (2015); B2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A common heterocyclic compound, 851768-35-9,5-Amino-3-methylbenzo[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. 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

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,851768-35-9,5-Amino-3-methylbenzo[d]isoxazole,its application will become more common.

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

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., 37924-85-9

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.

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

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.

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.

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.

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

89976-56-7 A common heterocyclic compound, 89976-56-7,5-Methylbenzo[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.

A mixture of 5-methylbenzo[d]isoxazol-3-amine (1.48 g, 10 mmol, 1.0 eq.), B0C2O (6.54 g, 30 mmol, 3.0 eq.), DMAP (122 mg, 1.0 mmol, 0.1 eq.), TEA (4.2 mL, 30 mmol, 3.0eq.) in DCM (30 mL) was refluxed for 18 h. The mixture was washed with water (30 mL X 2), dried over anhydrous Na2SC>4 and concentrated. The residue was purified via flash chromatography (PE/EA/DCM = 1/20/1-1/7/1, v/v/v) to afford tert-butyl [(tert- butoxy)-N-(5-methylbenz (3.2 g, 92%).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,5-Methylbenzo[d]isoxazol-3-amine,89976-56-7,its application will become more common.

Reference£º
Patent; LIFESCI PHARMACEUTICALS, INC.; MCDONALD, Andrew; WO2015/103317; (2015); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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. 36216-80-5

Example 149: N-(benzo[d]isoxazol-3-yl)-2,6-dimethoxybenzenesulfonamide 149 A solution of 2,6-dimethoxybenzene-1-sulfonyl chloride I111 (0.088 g, 0.37 mmol) and benzo[d]isoxazol-3-amine (0.050 g, 0.37 mmol) in pyridine (1 ml.) was irradiated in the microwave at 1 10 C for 2 hours, then at 120 C for 2 hours. The reaction mixture was loaded onto silica and purified by column chromatography (12g Si02 cartridge, 0-35 % EtOAc in petroleum benzine 40-60 C) to give the title compound (3.9 mg, 3.1 % yield) as a white solid. NMR (400 MHz, CDCIs) d 8.30 (s, 1H), 8.17 (dt, J = 1.04, 8.15 Hz, 1H), 7.55 – 7.47 (m, 1H), 7.47 – 7.34 (m, 2H), 7.34 – 7.28 (m,1H), 6.60 (d, J = 8.52 Hz, 2H), 3.91 (s, 6H). LCMS-B: rt 3.13 min, m/z = 334.8[M+H]+.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Benzo[d]isoxazol-3-amine,36216-80-5,its application will become more common.

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

A common heterocyclic compound, 828300-70-5,Benzo[d]isoxazol-6-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. 828300-70-5

A quantity of 0.13 g (1 mmole) OF BENZO [d] isoxazol-6-ylamine is treated with 0.27 g (1 mmole) of 6, 8-Dibromo-imidazo [1, 2-a] pyrazine in acetonitrile with 3 eq. OF K2C03 AT REFLUX for 16 hrs. The reaction mixture is cooled partitioned between ethyl acetate and water, the organic extracts are dried over anhydrous MGSO4 and evaporated in vacuo to afford Benzo [d] ISOXAZOL-6-YL- (6-BROMO- imidazo [1, 2-A] PYRAZIN-8-YL)-AMINE

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Benzo[d]isoxazol-6-amine,828300-70-5,its application will become more common.

Reference£º
Patent; CELLULAR GENOMICS, INC.; WO2005/5429; (2005); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

16263-54-0 A common heterocyclic compound, 16263-54-0,3,6-Dichlorobenzo[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.

5) Preparation 6-chloro-3-piperazinyl-benzisoxazole 3,6-dichlorobenzisoxazole (5.2g, 27.8 mmol), and anhydrous piperazine (24g, 278 mmol) are placed in an egg type flask and react at 120C for 24 hours. After completion of the reaction, 52 ml of an ice-water mixture is added for quenching the reaction. Further 15 ml of 50% NaOH solution is added to the reaction solution. The reaction solution is stirred for 5 minutes and extracted with dichloromethane (30ml*3). The dichloromethane layer is combined, washed with 20 ml of saturated saline, dried over anhydrous MgSO4, evaporated to dryness, and subjected to a separation on a column of alumina (200-300mesh), eluting with dichloromethane_methanol=100:1, to obtain 4.7g of 6-chloro-3-piperazinyl-benzisoxazole, with a yield of 71%.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,16263-54-0,3,6-Dichlorobenzo[d]isoxazole,its application will become more common.

Reference£º
Patent; Jiangsu Guohua Investment Co., Ltd; Shanghai Institute of Pharmaceutical Industry; EP2322520; (2011); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics