3-Amino-1,2-benzisoxazole

White to light brown solid

N-1, 2-Benzisoxazol-3-yl-4-(3-phenyl-1, 2, 4-thiadiazol-5-yl)piperazine-1-carboxamide; (1) 1, 2-Benzisoxazol-3-amine; To a solution of acetohydroxamic acid (10.0 g, 133 mmol) in N, N-dimethylformamide (150 ml) was added potassium tert-butoxide (14.9 g, 133 mmol), and the mixture was stirred at room temperature for 30 minutes. 2-Fluorobenzonitrile (18.0 g, 133 mmol) was added thereto, followed by stirring at room temperature for 5 hours. The reaction mixture was poured to water and extracted with ethyl acetate. The extract wase washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from hexane to give 4.80 g (27.0percent) of the desired product as a solid. 2- fluorobenzonitrile (6.1g, 50.0mmol), acetohydroxamic acid (5.6g, 75.0mmol) and potassium carbonate (10.4g, 75mmol) was dissolved in DMF (40mL), the mixture was stirred overnight and heated to 80 .With ethyl acetate (100mL × 2) and extracted.The combined organic phases were washed with water (100 mL × 2), saturated brine (100 mL), dried over anhydrous sodium sulfate.Filtered, and the solvent was evaporated under reduced pressure and the crude product purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 4/1), as a white solid (3.6g, 53.7percent).N-1, 2-Benzisoxazol-3-yl-4-(3-phenyl-1, 2, 4-thiadiazol-5-yl)piperazine-1-carboxamide; (1) Part C. Preparation of 1-(3-amino-1, 2-benzisoxazol-5-yl)-6-(2'-bromomethyl}-1, 1'-biphenyl-4-yl)-3-(trifluoromethyl)-1, 4, 5, 6-tetrahydro-7H-pryazolo[3, 4-c]pyridin-7-one To the aldehyde from Part B (2 g, 0.3.8 mmol) in 2:1 THF/MeOH (50 mL) at 0 C. was added NaBH4 (0.17 g, 0.46 mmol) and the reaction was stirred 30 min. The reaction was concentrated and partitioned between CH2Cl2/H2O. The organic layer was washed with brine and dried (MgSO4) to afford crude alcohol. To acetohydroxamic acid (0.89 g, 11.9 mmol) in DMF (5 mL) was added K2CO3 (2.139 g, 15.9 mmol) and several drops of water. After 30 min the above alcohol in DMF (15 mL) was added and the reaction was stirred 24 h. The reaction was concentrated, diluted with water and extracted with ethyl acetate, washed with water and brine and dried (MgSO4) to afford the crude aminobenzisoxazole.EXAMPLE 33 3-AMINOBENZISOXAZOLE 2-Hydroxy-O-carboethoxybenzamide oxime (1.5 grams) was heated to 135-140 C. under reduced pressure (5 mm.) and maintained at that temperature until the evolution of gas ceased (about 10 minutes). After cooling, ether was added and then the reaction mixture was filtered and chromatographed (ether-silica gel column chromatography). The material with the highest Rf value was a white solid which was identified by NMR and IR as the desired product, yield 500 mg.EXAMPLE 26 3-AMINOBENZISOXAZOLE 2-Hydroxy-O-carboethoxybenzamide oxime (1.5 grams) was heated to 135-140 C. under reduced pressure (5 mm.) and maintained at that temperature until the evolution of gas ceased (about 10 minutes). After cooling, ether was added and then the reaction mixture was filtered and chromatographed (ether-silica gel column chromatography). The material with the highest Rf value was a white solid which was identified by NMR and IR as the desired product, yield 500 mg.A mixture of

Molecular Weight:134.14
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:134.048012819
Monoisotopic Mass:134.048012819
Topological Polar Surface Area:52
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes