Methyl 2-aMino-5-chloropyridine-4-carboxylate synthesis

Yield: 16%

Reaction Conditions:

in N-methyl-acetamide;N-chloro-succinimide;ethyl acetate

Steps:

I.k.129 5-Chloro-2-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)isonicotinic acid
Example (Ik-129) 5-Chloro-2-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)isonicotinic acid 1.50 g (9.85 mmol) of methyl 2-aminoisonicotinate (commercially available) are stirred in 15 ml of dimethylformamide and admixed at a temperature of -18° C. in portions with 1.83 g (13.8 mol) of N-chlorosuccinimide. The mixture is then stirred for a further hour at -18° C. For work-up, the total reaction mixture is taken up in ethyl acetate and shaken against an aqueous sodium thiosulphate solution. The organic phase is then washed with water, dried over sodium sulphate and concentrated by evaporation in vacuo. The remaining residue is purified by means of column chromatography on silica gel using the eluent mixture cyclohexane:acetone (gradient). This gives 383 mg of methyl 2-amino-5-chloroisonicotinate (16%). ¹H-NMR (400 MHz, d₆-DMSO): δ=8.00 (s, 1H), 6.78 (s, 1H), 6.25 (br. s, 2H), 3.85 (s, 3H) ppm. HPLC-MS^a): log P=1.30; mass (m/z)=187 [M+H]⁺.

References:

Bayer CropScience AG US2011/301181, 2011, A1