3-Amino-6-bromo-1,2-benzisoxazole

Step A: 6-Bromobenzo[d]isoxazol-3-amine: N-hydroxyacetamide (1.13 g, 15.0 mmol) was dissolved in DMF (20 mL). To this was added KOt-Bu (1.68 g, 15.0 mmol) and the reaction was stirred for 30 minutes before addition of 4-bromo-2-fluorobenzonitrile (2.0 g, 10.0 mmol). The reaction mixture was left at ambient temperature for 2 hours, then diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate The combined organics were washed with water, dried, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with ethyl acetate/hexanes (1:4), ethyl acetate/hexanes (1:3) to give the desired product (1.35 g, 63percent). MS (APCI) m/z 215.2, 217.1 (M+1).Step A: 6-Bromobenzo[d]isoxazol-3-amine: N-hydroxyacetamide (1.13 g, 15.0 mmol) was dissolved in DMF (20 mL). To this was added KOt-Bu (1.68 g, 15.0 mmol) and the reaction was stirred for 30 minutes before addition of 4-bromo-2-fluorobenzonitrile (2.0 g, 10.0 mmol). The reaction mixture was left at ambient temperature for 2 hours, then diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate The combined organics were washed with water, dried, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with ethyl acetate/hexanes (1:4), ethyl acetate/hexanes (1:3) to give the desired product (1.35 g, 63%). MS (APCI) m/z 215.2, 217.1 (M+1).To a solution of 6-bromobenzo[d]isoxazol-3 -amine (1.0 g, 4.7 mmol) and cyclopropylboronic acid (0.81 g, 9.4 mmol) in a mixture of toluene (10 mL) and water (1.0 mL) under nitrogen at room temperature were added potassium phosphate (1.0 g, 9.4 mmol), palladium acetate (53 mg, 0.2 mmol) and tricyclohexylphosphine (0.11 g, 0.4 mmol). The resulting mixture was stirred at 100 C for 6 hours, then diluted with water (10 mL) and extracted with ethyl acetate (3 x 10 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vaccuo. The residue was purified by silica gel chromatography [petroleum ether: ethyl acetate = 5: 1] to afford compound A-4 (0.59 g, 72% yield) as a off-white solid. LCMS (B): tR=0.684 min., (ES+) m/z (M+H)+ = 175.1. -NMR (CD3OD, , 400 MHz): delta 7.40-7.38 (d, J=8.0 Hz, 1H), 7.09 (s, 1H), 6.99-6.97 (d, J=8.4 Hz, 1H), 4.37 (s, 2H), 2.05-2.01 (m, 1H), 1.10-1.05 (m, 2H), 0.81-0.77 (m, 2H).{'43). To a solution of the starting material (75 mg, 0, 3500mmoi) and triethyam e (0.06 mL, 0.42 mmoij in DCM (3 raL, 0, 1 M) was added ptvaloyi chloride (0, 05 mL, 0.42 romot j , After 3 hours at it, the reaction was heated to 30 'C for 12 hrs, and monitored via LCMS. The reaction was concentrated, and purified using flash chromatography on silica gel (8-30% EtOAc in hexanes) to provide 43 (41.7 mg, 0.14 ramoi, 40% yield).

Molecular Weight:213.03
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:211.95853
Monoisotopic Mass:211.95853
Topological Polar Surface Area:52
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes