Oxazolidinone derivative and preparation method and application thereof
A technology for drugs and compounds, applied in the field of blood coagulation, can solve the problems such as difficulty in purifying rivaroxaban, and achieve the effects of low price, easy purification and easy preparation
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Embodiment 1
[0046] (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3-oxazolidine-5- Base) methyl) thiophene-2-carboxamide (I-1)
[0047]
[0048] Synthesis of A, 1-(4-aminophenyl)-1H-pyridin-2-one (compound VII)
[0049] Add 104g pyridin-2(1H)-one (compound IX), 200g p-iodoaniline (compound VIII), 26gCuI, 151g potassium carbonate, 18g8-hydroxyquinoline, 500mlDMF, nitrogen protection, heating and reflux, insulated and stirring reaction in the reaction flask 10h. Filtrate while hot, take the filtrate, evaporate the solvent under reduced pressure, add 1L of ethyl acetate to the residue, keep stirring at 0°C for 1 hour, filter, dry the solid, and refine it with 2L of acetonitrile to obtain 98g of a dark red solid. The refined mother liquor was concentrated to 500ml, stirred in an ice bath for 1h, and filtered to obtain 19g of a dark red solid. A total of 117g of the product was obtained, with a yield of 68.9%.
[0050] 1 H-NMR (DMSO-d 6 ), δ (ppm): 5.306 (s, 2H), 6.236 (...
Embodiment 2
[0074] (S)-5-bromo-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3-oxazolidine-5- Base) methyl) thiophene-2-carboxamide (I-2)
[0075]
[0076] Melting point: 200.8~201.8℃;
[0077] 1 H-NMR (DMSO-d 6 ), δ(ppm): 3.580(t, 2H), 3.902(m, 1H), 4.221(t, 1H), 4.849(m, 1H), 6.308(t, 1H), 6.468(d, 1H), 7.193 (d, 1H), 7.426(m, 2H), 7.500(m, 1H), 7.637(m, 4H), 8.967(t, 1H);
[0078] MS(ESI): m / z=474(M+H);
[0079] HPLC: rt(%)=13.44(99.55);
[0080] [α] 20 D = -32.9° (c 0.3010, DMSO);
Embodiment 3
[0082] (S)-5-methyl-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3-oxazolidine-5 -yl)methyl)thiophene-2-carboxamide (I-3)
[0083]
[0084] 1 H-NMR (DMSO-d 6 ), δ(ppm): 3.457(s, 3H), 3.600(t, 2H), 3.897(m, 1H), 4.224(t, 1H), 4.860(m, 1H), 6.314(t, 1H), 6.468 (d, 1H), 6.842 (d, 1H), 7.419 (d, 2H), 7.499 (m, 1H), 7.622 (m, 4H), 8.724 (t, 1H).
[0085] MS(ESI): m / z=410(M+H);
[0086] In the HPLC data that provides in the above-mentioned embodiment, the unit of retention time rt is minute, and HPLC parameter is:
[0087]Instrument: Waters 996-717-600 liquid chromatograph; Column: GL Science C18 column; Column temperature: 45°C; Eluent: phase A is potassium dihydrogen phosphate solution, phase B is potassium dihydrogen phosphate solution-acetonitrile ( 20:80); detection wavelength: 233nm; flow rate: 1.2ml / ml; gradient: 0.0min 55%A→5min 55%A→10min 40%A→20min 0%A→35min 0%A→36min 55%A.
[0088] In order to more fully illustrate the practice of the present invention, the fo...
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