Pyridine → HCID 53419570, compound

A solution of 2-bromo-5-nitroaniline (500 mg, 2.30 mmol) in THF (40 mL) was treated with pyridine (0.19 mL, 2.3 mmol) and methyl chloroformate (0.27 mL, 3.5 mmol) at room temperature. After 4 hours, additional methyl chloroformate (0.27 mL, 3.5 mmol) was added, and the reaction mixture was stirred at room temperature for an additional 3 hours. The reaction mixture was concentrated to dryness and then taken up in EtOAc (30 mL) and washed with 1 N HCl (3×25 mL), dried (Na2SO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM and purified by flash chromatography (SiO2, 0% ethyl acetate/hexanes to 30% ethyl acetate/hexanes, 40 g column, 30 min. gradient) to afford Intermediate 60A (390 mg, 61.5%). HPLC: Rt=3.215 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min gradient, monitored at 220 nm). MS (ES): m/z=274.9 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.39 (1H, s), 8.44 (1H, d, J=2.52 Hz), 7.92-7.96 (1H, m), 7.88-7.92 (1H, m), 3.71 (3H, s).

1. concentrationThe reaction mixture was concentrated to dryness
2. washwashed with 1 N HCl (3×25 mL)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe crude product was dissolved in a small amount of DCM
7. custompurified by flash chromatography (SiO2, 0% ethyl acetate/hexanes to 30% ethyl acetate/hexanes, 40 g column, 30 min. gradient)

ORD record

ord-da40ee00c7f2427baaa786e85bb7512f

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08252795B2