Heterocyclic Building Blocks-Benzisoxazole

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

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.

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.

Reference£º
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/111038; (2005); A2;,
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

A mixture of benzo[d]isoxazol-3-ylamine (3.0 g) and CICO2Ph (0.94 ml_) in dry CH3CN (30 ml_) was stirred for 23 h at 70 0C. The reaction mixture was poured into de- ionized water, stirred for 30 min and filtered. The isolated solid was rinsed thoroughly with water and then dried under high vacuum to give 1.90 g (100%) of the title compound. MS: 255.1.

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

Reference£º
Patent; JANSSEN PHARMACEUTICA N.V.; WO2008/153752; (2008); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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. 239097-74-6

Synthesis of N-benzofdlisoxazol-5-yl-4-propyl-benzenesulfonamide, STX 919 (KRB01047) :; To a solution of 4n-propylbenzenesulphonyl chloride (171 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 (170 mg, 72%), single spot at Rf 0.68 (1: 1 hexane: ethyl acetate). mp 130.0- 130. 6C, HPLC purity 99+% (tR 2.44 min in 10% water-acetonitrile).’H NMR (CDCI3) : No. 8.62 (1H, d, J=1.0 Hz), 7.60 (2H, d, J=8.4 Hz), 7.48 (2H, m), 7.19 (3H, m), 6.86 (1H, s, N-H), 2.58 (2H, t, J=7.5 Hz), 1.58 (2H, sextet, J=7.4 Hz), 0.88 (3H, t, J=7.4 Hz). LCMS: 315.14 (M-). FAB-MS (MH+, deHOsS) : calcd 317.0960, found 317.0962, 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,239097-74-6,Benzo[d]isoxazol-5-amine,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, 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

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,36216-80-5,Benzo[d]isoxazol-3-amine,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, 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 77; (3R)-1-[2-(1,2-Benzisoxazol-3-ylamino)-2-oxoethyl]-3-{[2-piperidin-1-yl-2-(2-thienyl)propanoyl]oxy}-1-azoniabicyclo[2.2.2]octane chloride (Isomer 1); a) N-1,2-Benzisoxazol-3-yl-2-chloroacetamide; Benzo[d]isoxazol-3-amine (1 g) and cesium carbonate (2.429 g) in dry DMF (20 mL) was stirred at 23 C. whilst bromoacetyl chloride (0.624 mL) was added dropwise to the mixture. After stirring for 8 h, the reaction was poured into water (100 mL) and the mixture extracted with diethyl ether (2¡Á200 mL). The combined extracts were dried over magnesium sulfate and concentrated to dryness. The crude product was purified on silica gel using 40% ether isohexane. The subtitled compound was isolated as a colourless solid (0.5 g).m/e 210 [M+H]+ 1H NMR (400 MHz, DMSO) delta 11.45 (1H, s), 8.02 (1H, d), 7.72-7.63 (2H, m), 7.39 (1H, ddd), 4.47 (2H, s).

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; Ford, Rhonan; Mete, Antonio; Millichip, Ian; Teobald, Barry; US2010/113510; (2010); A1;,
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 3-chloro-2-methyl-N-(3-methyl-benzo[d]isoxazol-5-yl)- benzenesulfonamide, STX 874 (KRB01027):; To a solution of 3-chloro-2-methylbenzenesulphonyl chloride (128 mg, 0.567 mmol) in dichloromethane (3 mL) was added pyridine (110 muL, 1.35 mmol) and the mixture was stirred under N2 for 5 min, after which time 5-amino-3-methyl-1, 2-benzisoxazole [26] (80 mg, 0.54 mmol) was added. The resulting mixture was stirred for 4 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 white solid (88 mg, 48%), single spot at Rf 0.58 (1: 1 hexane: ethyl acetate). mp 162.8-163. 2C, HPLC purity 99+% (tR 2.26 min in 10% water- acetonitrile).’H NMR (CDC13) : 6 7.80 (1H, dd, J=7.9, 1.3 Hz), 7.55 (1H, dd, J=8. 1, 1.1 Hz), 7.38 (2H, m), 7.17 (1 H, t, J=8.1 Hz), 7.10 (1H, dd, J=8.8, 2.2 Hz), 6.72 (1H, s, N-lez 2.72 (3H, s), 2.50 (3H, s). LCMS: 320.00 (M-CH3). FAB-MS (MH+, C15H13ClN2O3S) : calcd 337.0413, found 337.0422.

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

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

Benzisoxazole-3-amine 2 (2.68 g, 20 mmol) was dissolved in water (25 ml) and concentrated HCl (12.5 ml) under vigorous stirring in an ice/water bath. A freshly prepared, ice-cold solution of NaNO2 (1.4 g, 20 mmol) in water (10 ml) was added drop wise to the reaction mixture by keeping the internal temperature between 0 to 5 C. After the completion of addition, the reaction mixture was stirred for an additional 10 min. A freshly prepared solution of sodium azide (1.3 g, 20 mmol) in water (10 ml) was added drop wise to the reaction mixture via an additional funnel while keeping the internal temperature of the reaction mixture below 5 C. Upon complete addition of the sodium azide solution, the reaction mixture was stirred for an additional 20-30 min at 0 C, followed by stirring at room temperature for another 3 h. The reaction mixture was extracted with ethyl acetate EtOAc (25 ml) three times. The combined organic layer was washed with water (25 ml) and brine (25 ml), dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude benzisoxazole-3-azide 3, which was purified by column chromatography over silica gel (60-120 mesh) using hexane/EtOAc (8:2) as eluent. The pure benzisoxazole-3-azide 3 was stored at 2-5 C in the refrigerator.

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

Reference£º
Article; Ashwini, Nanjundaswamy; Garg, Manoj; Mohan, Chakrabhavi Dhananjaya; Fuchs, Julian E.; Rangappa, Shobith; Anusha, Sebastian; Swaroop, Toreshettahally Ramesh; Rakesh, Kodagahalli S.; Kanojia, Deepika; Madan, Vikas; Bender, Andreas; Koeffler, H. Phillip; Basappa; Rangappa, Kanchugarakoppal S.; Bioorganic and Medicinal Chemistry; vol. 23; 18; (2015); p. 6157 – 6165;,
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.

651780-27-7, Toluene (40 mL) was added to a flask containing ethyl [6-BROM-1,] 2-benzisoxazole-3-carboxylate (3.15 g, 11.7 mmol), tetrakis (triphenylphosphine) palladium [(0)] (835 mg, 0.723 mmol, Strem), cesium carbonate (4.12 g, 12.6 mmol, Aldrich), and 2- (trifluoromethyl) phenylboronic acid (2. [38] g, 12.5 mmol, Aldrich) under argon. This mixture was heated in a 100 C oil bath for 35 hours. The mixture was diluted with EtOAc (250 mL) and washed with 4: 1 water: brine (250 [ML)] followed by brine (250 mL). The organics were filtered through a [1″PLUG] of silica gel and evaporated. Product was split in two, adsorbed onto silica gel, and purified on Biotage Flash 40 M+ silica cartridges using 20% EtOAc in heptane. Yield was 2.08 g of orange solid. [‘H] NMR (400 MHz, DMSO-d6) [5] ppm 1.42 (t, [J=7.] 15 Hz, 3 H) 4.51 (q, [J=7.] 05 Hz, 2 H) 7.52 (d, J=7. 46 Hz, [1] H) 7.51 (d, [J=8.] 09 Hz, 1 H) 7.71 (t, J=7. 57 Hz, [1] H) 7.79 (t, [J=7.] 36 Hz, 1 H) 7.91 (d, [J=7.] 67 Hz, [1] [H)] 7.93 (s, 1 H) 8.14 (d, J=8. 09 Hz, 1 H).

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; PHARMACIA & UPJOHN COMPANY; WO2004/18428; (2004); 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

36216-80-5, EXAMPLE 7 N-[2-(4-Morpholinyl)ethyl]-1,2-benzisoxazol-3-amine To a solution of 3-amino-1,2-benzisoxazole (3.5 g) in N,N-dimethylformamide (DMF) (100 ml) was added sodium hydride (0.8 g) under nitrogen. The reaction was stirred one hour at ambient temperature. A solution of 4-(2-chloroethyl)morpholine (4.0 g) in DMF (50 ml) was added followed by heating to 120 C. for one hour. TLC (5% MeOH/DCM) analysis revealed the absence of starting material. The reaction was quenched with water and extracted with EtOAc. The organic layer was washed with water, dried (MgSO4), and concentrated in vacuo. Flash column chromatography (silica gel) eluding with 1.5-2.5% MeOH/DCM afforded the product (2.5 g), m.p. 79-80 C. ANALYSIS: Calculated for C13 H17 N3 O2: 63.14%C 6.93%H 16.99%N Found: 63.47%C 6.87%H 16.95%N

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; Hoechst-Roussel Pharmaceutical Incorporated; US5494908; (1996); A;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

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.

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.

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