2-Amino-4,6-dichloro-nicotinicacidmethylester

Step 116-2 The compound (30 g) obtained in step 116-1, phosphorus oxychloride (150 ml) and N, N-diisopropylethylamine (30 ml) were mixed, and the mixture was stirred at room temperature for 3 days. The reaction mixture was concentrated, and azeotropically distilled 3 times with toluene. Under ice-cooling, methanol (30 ml) and water (150 ml) were added and the mixture was stirred at room temperature for 1 hr. The resulting solid was collected by filtration, and combined with the solid resulting from the filtrate. Methanol (50 ml) was added and the mixture was stirred at room temperature for 1 hr. The solid was collected by filtration to give primary crystals. The filtrate was concentrated, and methanol (10 ml) was added to the residue, and the resulting solid was collected by filtration to give a secondary crystal. The primary crystal and the secondary crystal were combined to give the compound described in the above-mentioned scheme (21 g, 59percent).A mixture of dimethyl acetone-1, 3-dicarboxylate (200 g, 1.15 mol), cyanamide (48.3 g, 1.15 mol), and Ni(acac)Phosphorous oxychloride (225 mL) was added to methyl 2-amino-4, 6-dihydroxy- pyridine-3-carboxylate (44 g, 0.239 mol) at 0 °C under nitrogen atmosphere. To this reaction mixture was added Ν, Ν-diisopropylethyl amine (44 mL) at the same temperature and the reaction mixture was stirred at RT for 3 d. The progress of reaction monitored by TLC and LCMS. After completion of reaction, the reaction mixture was concentrated under reduced pressure to obtain a sticky compound which was cooled to 0 °C and MeOH (40 mL) and water (200 mL) were added. The reaction mixture was stirred at RT for 1 h. The resulting solid was filtered off and purified by column chromatography on silica (100:200 mesh) using 10percent EtOAc-hexane system as eluent to afford methyl 2-amino-4, 6-dichloro-pyridine-3-carboxylate (20 g).Example 63 To a solution of methyl 2-amino-4, 6-dichloro-pyridine-3-carboxylate (300 mg, 1.357 mmol) in dry THF (7 mL) was added a 3M solution of methylmagnesium bromide in diethyl ether (1.58 mL, 4.75 mmol) dropwise under nitrogen at -60 C. The reaction mixture was stirred at -60 C to 0 C for 1 h. The progress of reaction was monitored by TLC & 1H NMR. After completion of reaction, the mixture was quenched using aqueous saturated solution of ammonium chloride and extracted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography on silica (100:200 mesh) using 10% EtOAc-hexane system as eluent to afford 2-(2-amino-4, 6-dichloro-3-pyridyl)propan- 2-ol (263 mg).

Molecular Weight:221.04
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:219.9806328
Monoisotopic Mass:219.9806328
Topological Polar Surface Area:65.2
Heavy Atom Count:13
Complexity:203
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes