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The reaction with <strong>[1227002-03-0]methyl 2-amino-5-chloroisonicotinate</strong> takes place analogously to the reaction procedure in Example (Ik-127) using: 601 mg (3.21 mmol) of <strong>[1227002-03-0]methyl 2-amino-5-chloroisonicotinate</strong> in 28.0 ml of dichloromethane, 1064 mg (3.21 mmol) of 1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride, 431 mg of silver(I) cyanide in 28.0 ml of acetonitrile. The remaining residue is purified by means of column chromatography on silica gel using the eluent mixture cyclohexane:acetone (gradient). This gives 563 mg of methyl 5-chloro-2-([1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)-isonicotinate (36%).
In N-methyl-acetamide; N-chloro-succinimide; ethyl acetate;
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): delta=8.00 (s, 1H), 6.78 (s, 1H), 6.25 (br. s, 2H), 3.85 (s, 3H) ppm. HPLC-MSa): log P=1.30; mass (m/z)=187 [M+H]+.
With dmap; triethylamine; In N,N-dimethyl-formamide; at 20.0℃; for 72.0h;
To a solution of <strong>[1227002-03-0]methyl 2-amino-5-chloroisonicotinate</strong> (4.75 g, 25.5 mmol) in DMF (40 mL) was added 4-(dimethylamino)pyridine (0.466 g, 3.82 mmol), triethylamine (10.62 mL, 76 mmol), and di-tert-butyl dicarbonate (16.67 g, 76 mmol). The reaction was stirred at room temperature for 3 d. The reaction was quenched with water (40 mL). The aqueous layer was extracted with EtOAc (100 mL, three times), and the combined organic layers were washed with water, brine, dried (MgS04) and concentrated. The residue was purified by flash chromatography (80 g silica gel column, gradient elution from hexanes to 15% EtOAc/hexanes) to provide bis-Boc aminopyridine (6.36 g, 16.44 mmol) as a white powder.
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