Oxazolidinone compound containing pyridine and preparation method thereof
A technology of compound and alkyl, applied in the field of medicinal chemistry, can solve the problems such as the reduction of curative effect
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Embodiment 1
[0056] Example 1 N-[[(5S)-3-fluoro-4-(2-aminopyrimidin-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide preparation of
[0057] 1.1 Preparation of N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (IV)
[0058] 1.1.1 Preparation of (S)-1-amino-3-chloro-2-propanol hydrochloride
[0059] Dissolve 59.0g (0.56mol) of benzaldehyde in 150ml of ethanol, add dropwise 58.0ml (0.55mol) of ammonia water to the reaction solution, stir, and dropwise add 58ml (0.88mol) of (S)-epichlorohydrin to the reaction solution , Control the rate of addition to keep the reaction temperature below 40°C. After dropping, react at 35-40°C for 6h, then lower the reaction solution to room temperature and continue to react for 12h. Most of the solvent was distilled off under reduced pressure, and 100 ml of toluene was added. After stirring, the solution was raised to 35-40°C, and an aqueous hydrochloric acid solution (68ml hydrochloric acid, 77ml water) was added dropwise, and the solution was stirred at 35-40°C...
Embodiment 2
[0073] Example 2 N-[[(5S)-3-fluoro-4-(2-aminopyrimidin-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Preparation of hydrochloride
[0074] N-[[(5S)-3-fluoro-4-(2-aminopyrimidin-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide 5.2g (0.015mol) was added to 80% ethanol, under stirring, hydrochloric acid ethanol solution was added dropwise to pH = 2, heated to reflux, activated carbon was decolorized, filtered while hot, and dried to obtain N-[[(5S)-3-fluoro-4 -(2-aminopyrimidin-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide hydrochloride 5.4 g, yield 95.1%. mp: 227.3°C; [α] 20 D =-25.3 (c=1.00, DMSO).
Embodiment 3
[0075] Example 3 N-[[(5S)-3-fluoro-4-(2-aminopyrimidin-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Preparation of mesylate
[0076] N-[[(5S)-3-fluoro-4-(2-aminopyrimidin-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide 5.2g (0.015mol) was added to 80% ethanol, methanesulfonic acid was added dropwise under stirring until pH = 2, heated to reflux, activated carbon was decolorized, filtered while hot, and dried to obtain N-[[(5S)-3-fluoro-4 -(2-aminopyrimidin-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide methanesulfonate 6.2 g, yield 93.9%.
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