[Cesium Bicarbonate Label: Title] Background and Overview
2-Chloro-3-nitro-4-methoxypyridine can be used as a pharmaceutical synthesis intermediate. It can be prepared by reacting 2,4-dichloro-3-nitropyridine with NaOMe as the reaction raw material. It can be used To prepare another pharmaceutical intermediate 1-cyclohexyl-4-(4-methoxy-3-nitro-pyridin-2-yl)-piperazine.
Preparation and application of 2-chloro-3-nitro-4-methoxypyridine
Add NaOMe (0.91g, 16.81mmol) in batches to the 2,4-dichloro-3-nitropyridine (2.23g, 11.21mmol) solution at 0°C, stir at room temperature for 2 hours, and then add NaOMe ( 182 mg, 3.36 mmol), and the reaction mixture was stirred for 4 h. The mixture was concentrated in vacuo, diluted with DCM, washed with saturated aqueous NH4Cl then H2O, dried over MgSO4 and concentrated in vacuo to give the crude title 2-chloro-3-nitro-4-methoxypyridine as a beige solid, Yield (2.12g, 10.51mmol, 93%). HPLC: AtRet=4.53 minutes; m/z (M+H)+. LC-MS: m/z187.0[M-H]+.
Preparation and application of 2-chloro-3-nitro-4-methoxypyridine
2-Chloro-3-nitro-4-methoxypyridine can be used to prepare the pharmaceutical intermediate 1-cyclohexyl-4-(4-methoxy-3-nitro-pyridin-2-yl)- Piperazine: To a solution of 2-chloro-3-nitro-4-methoxypyridine (4.25 mmol) in acetonitrile (20 mL) at 0°C, K2CO3 (1.76g, 12.76mmol) and 1-cyclohexyl-piperazine (787mg, 4.68mmol), remove the ice bath, stir the orange suspension at room temperature overnight, filter out the inorganic salts and wash with THF for several times times, the filtrate was concentrated in vacuo, and the residue was subjected to silica gel column chromatography (using a gradient elution of DCM:EtOAc=100:0 to 0:100) to obtain 1-cyclohexyl-4-(4-methoxy- 3-Nitro-pyridin-2-yl)-piperazine (1.04 g, 3.21 mmol, 59.6%) as a yellow solid. HPLC: AtRet=4.02 min; m/z (MH+), LC-MS: m/z 321. Methylpyridine 2.
References
[1] WO2012176123 – 3 – IMIDAZOLYL- INDOLES FOR THE TREATMENT OF PROLIFERATIVE DISEASES
