5-BROMO-7-INDAZOLECARBOXYLIC ACID METHYL ESTER

To a mixture of 19-S3 (10.9 g, 44.7 mmol) and AcOK (1.32 g, 13.41 mmol) in CHC13 (50 mL) was added Ac20 (10.6 g, 103 mmol) at 0 °C slowly under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 1 hour. The mixture was then heated to 60 °C and t-BuONO (10.2 g, 98.3mmol) was added to the above mixture. The resulting mixture was stirred at 60 °C for 4 hours. After cooling, the mixture was quenched with saturated aqueous NaHCO3 solution and extracted with EtOAc. The organic layer was separated, dried, and concentrated to afford the crude product, which was purified by column chromatography on silica gel (eluted with PE/EtOAc = 100:0 to 10:1) to afford 19-S4 (8.0 g, 70.5percent yield) as a yellow solid. LC/IVIS (ESI) m/z: 255 (M+H).[0394j Acetic anhydride (4.5 g, 4.1 mL, 44 mmol) was added dropwise to the homogenous solution ofmethyl 2-amino-5-bromo-3-methylbenzoate (4.72 g, 19 mmol) in chloroform (55 mL) over a period of 20 mm at room temperature and allowed to stir for lh. Potassium acetate (5.7 g, 58 mmol) and isoamyl nitrate (6.6 g, 7.6 mL, 57 mmol) were added at once to the reaction mixture under nitrogen. The clear reaction mixture turned to dark upon heating at 90 °C. The reaction mixture was cooled to room temperature after overnight reflux , concentrated, diluted with water and stirred. The beige solid formed was collected by filtration and dried to obtain methyl 5-bromo-1H-indazole-7-carboxylate(2.1 g , 42percent).’H NMR (DMSO-d6): ö 13.44 (s, 1H), 8.33 (s, 1H), 8.21 (s, 1H), 7.99 (s, 1H), 3.95 (s, 3H). LCMS: rt 6.86 mill (A), purity 99 percent, MS (mle) 255 (MHjCompound 6a (0.30g, 1.00mmol) was dissolved in MeOH (5mL) and treated with 6N HCl (2ml). The reaction mixture was stirred at rt for 2h and then concentrated under reduced pressure. The residue was taken with EtOAc and washed with water. The organic layer was concentrated to give the desired methyl 5-bromo-1H-indazole-7-carboxylate (6b) as a bright brown solid (0.25g, 98percent yield): To a stirred solution of methyl 2-amino-5-bromo-3-methylbenzoate (5) (0.50 g, 2.20 mmol) in CHCl

Molecular Weight:255.07
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:253.96909
Monoisotopic Mass:253.96909
Topological Polar Surface Area:55
Heavy Atom Count:14
Complexity:237
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes