Ethyl 5-amino-2-chloropyridine-4-carboxylate synthesis

Yield:862314-10-1 41%

Reaction Conditions:

with N-chloro-succinimide in N,N-dimethyl-formamide at 20 - 50; for 18 h;Inert atmosphere;

Steps:

56.56.A 56A): Ethyl 5-amino-2-chloroisonicotinate

To a solution of ethyl 3-aminoisonicotinate (4.0 g, 24.07 mmol) in DMF (25 mL) was added NCS (3.54 g, 26.5 mmol) at room temperature. The reaction mixture was then heated at 50° C. under nitrogen for 18 h. The reaction mixture was cooled to room temperature and treated with saturated aqueous NaHCO₃ solution and ethyl acetate. The organic layer was separated and washed with brine, dried (MgSO₄) and filtered. The filtrate was concentrated in vacuo. The residue was dissolved in DCM and purified by silica gel flash chromatography, eluting with 30% ethyl acetate in hexane to give the desired product as a light yellow solid (2.0 g, 41%); HPLC: RT=0.84 min (H₂O/ACN with 0.05% TFA, Waters Acquity SDS BEH C18, 2.1×50 mm, 1.7-μm particles, gradient=1.8 min, wavelength=220 nm); MS (ES): m/z=200.9 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ ppm 7.98 (d, J=0.4 Hz, 1H), 7.66 (d, J=0.4 Hz, 1H), 4.38 (q, J=7.3 Hz, 2H), 1.42 (t, J=7.2 Hz, 3H).

References:

US2016/176871,2016,A1 Location in patent:Paragraph 0495-0496