1H-Indazole-1-carboxylic acid, 2,3-dihydro-5-nitro-3-oxo-, 1,1-diMethylethyl ester synthesis

Yield:876343-67-8 61%

Reaction Conditions:

Stage #1: 5-nitroindazolin-3-onewith sodium hydrogencarbonate in water; for 0.5 h;
Stage #2: di-tert-butyl dicarbonate in water at 45;

Steps:

19.C

19B (0.500 g, 2.319 mmol) was mixed with water (10 mL). To this solution/suspension sodium bicarbonate (0.214 g, 2.55 mmol) was added portionwise. The mixture was stirred for 30 min. BOC-Anhydride (0.700 mL, 3.01 mmol) was added, the mixture was heated to 45 ⁰C and stirred at this temperature for 30 min. Additional portions of sodium bicarbonate (totaling 1.5 g) and BoC₂O (totaling 1 g) were added and the mixture was stirred overnight at 45 ⁰C. The reaction mixture was diluted with water (100 mL), and extracted with EtOAc (3 x 25 mL). The combined organic phase was washed with water (2 x 50 mL), brine (1 x 50 mL) and dried (Na₂SO₄). After filtration, the solvent removed under reduced pressure and the resulting solid was washed with ether/hexanes (3x) and dried to give 19C (0.395 g, 1.415 mmol, 61.0 % yield) as a yellowish solid. LC-MS: (Phenom. Luna C18 30x4.6mm 5u; sol. A 10% MeCN - 90% H₂O - 0.1% TFA; sol. B 90% MeCN - 10% H₂O - 0.1% TFA; wavelength 220 nm; flow rate 5 mL/min; gradient time 2 min; start % B = 0%, final % B = 100%) 1.217 min, [M+lf = 280.02. Purity >95%. ¹H-NMR: (400 MHz, DMSO-d₆) δ ppm 1.61 (s, 9 H) 8.13 (d, J=9.34 Hz, 1 H) 8.40 (dd, J=9.34, 2.20 Hz, 1 H) 8.57 (d, J=2.20 Hz, 1 H) 12.60 (s, 1 H). ¹³C-NMR: (101 MHz, DMSO- d₆) δ ppm 27.69, 84.56, 114.97, 116.99, 117.24, 124.60, 143.02, 148.21, 158.48.

References:

WO2008/79759,2008,A1 Location in patent:Page/Page column 130