Electric Literature of 104508-24-9 ,Some common heterocyclic compound, 104508-24-9, molecular formula is C7H5BrN2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
Racemic 2,2-difluoro-8-(1-hydroxyethyl)-2H-1 ,4-benzoxazin-3(4H)-one (50 mg; may be prepared as described in intermediate 4), 6-(bromomethyl)-2-pyridinecarbonitrile (64.5 mg, may be prepared as described in intermediate 39), potassium carbonate (60.3 mg, 0.436 mmol) and potassium iodide (0.362 mg, 2.182 mumol) were dissolved in DMF (2000 mul) in a 10 ml. round-bottomed flask open to the atmosphere and stirred at room temperature overnight. The reaction mixture was evaporated to dryness, redissolved in EtOAc (30ml) and treated with saturated aqueous sodium bicarbonate (30ml). The aqueous layer was extracted with EtOAc (2x30ml) and the organic layers were combined, washed with brine (30ml), dried over magnesium sulfate, fiitered and evaporated to dryness to give the crude product (94mg) as a pale yellow oil. The crude product was purified on a 25+S Biotage silica cartridge, eluting with a 0 to 70 % mixture of EtOAc in hexane to give a colourless oil (67 mg). 53 mg of this racemic mixture was resolved using a Chiralpak IA column eluting with heptane: ethanol (80:20) v/v pump- mixed. Using these conditions the faster-running enantiomer (18 mg, Compound 61 or 62) and the slower-running enantiomer (17 mg, Compound 61 or 62) were obtained in >98% enantiomeric excess as white solids. 1H NMR (CD3OD) delta: 1.45 (3H, d), 5.24 (1 H, q), 5.43 (2H, s), 7.10 (1 H, dd), 7.20 (1 H, t), 7.39, (1 H, d), 7.65 (1 H, d), 7.78 (1 H, d), 7.98 (1 H, t). m/z [M+H]+: 346.2. Retention time 0.91 min (LC/MS method 3).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,104508-24-9, its application will become more common.
Reference:
Patent; GLAXO GROUP LIMITED; BLUNT, Richard; EATHERTON, Andrew John; GARZYA, Vincenzo; HEALY, Mark Patrick; MYATT, James; PORTER, Roderick Alan; WO2011/12622; (2011); A1;,
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