Synthesis and Reactivity of an 1,3-Oxazin-6-one Derived from α-Aminophosphonate

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• “ Synthetic procedure for the preparation of diethyl 2-(dimethylamino)-6-oxo-6H-1,3-oxazin-4-ylphosphonate 1: To a stirred solution of enamine 5 9 (1 g, 4 mmol) in toluene (50 mL), N-(dichloromethylene)-N-methylmethanaminium chloride 8 (1.95 g, 12.0 mmol) was added. The mixture was refluxed for 48 h, and the solvent removed by evaporation under reduced pressure. The crude product was washed with water and extracted twice with dichloromethane (20 mL). Combined organic layers were washed with Na2CO3 (sat. solution), H2O, and NaCl (sat. solution), and then dried over MgSO4. After filtration, the crude product was purified by flash-column chromatography (silica gel, AcOEt:hexane, 50:50) to afford 3 (0.55 g, 50%) as a yellow oil. Selected data of 1: 1H NMR (300 MHz, CDCl3): δ = 6.01 (d, 3 J PH = 10.2 Hz, 1H, HC˭C), 4.19 (m, 4H, 2 x CH2), 3.15 (s, 3H, NCH3), 3.09 (s, 3H, NCH3), 1.32 (t, 3 J HH = 6.95 Hz, 3H, CH 3‒CH2), 1.31 (t, 3 J HH = 6.95 Hz, 3H, CH 3‒CH2). 13C NMR (75 MHz, CDCl3): δ = 160.80 (d, 1 J PC = 217.1 Hz, C‒P), 159.12 (d, 3 J PC = 34.2 Hz, N‒C(O)˭N), 157.21 (d, 3 J PC = 20.1 Hz, C˭O), 99.45 (d, 2 J PC = 22.2 Hz, C˭C‒P), 62.96 (s, CH2‒O), 62.88 (s, CH2‒O), 36.81 (s, CH3‒N), 35.43 (s, CH3‒N), 15.66 (s, CH3‒CH2‒O), 15.58 (s, CH3‒CH2‒O). 31P NMR (120 MHz, CDCl3): δ = 8.56. MS(EI): m/z (%) = 276 (M+, 8), 176 (100) ” .
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• “ Synthetic procedure for the preparation of diethyl 1-(3,3-dimethylureido)-3-oxo-3-(pyrrolidin-1-yl)prop-1-enylphosphonate 12: To a stirred solution of oxazinone 1 (0.02 g, 0.07 mmol) in chloroform (5 mL), pyrrolidine (0.02 g, 0.3 mmol) was added. The mixture was stirred for 3 h at room temperature, and the organic layer washed with Na2CO3 (sat. solution), H2O, and NaCl (sat. solution), and then dried over MgSO4. After filtration, the crude product was purified by flash-column chromatography (silica gel, AcOEt and then AcOEt:methanol 90:10) to afford 12 (0.02 g, 74%) as a yellow oil. Selected data of 12: 1H NMR (300 MHz, CDCl3): δ = 11.87 (d, 3 J PH = 25.8 Hz, 1H, NH), 6.02 (d, 3 J PH = 15.4 Hz, 1H, HC˭C), 4.25 (m, 4H, 2 x CH2‒O), 3.51 (m, 4H, 2 x CH2‒N), 3.02 (s, 6H, N(CH3)2), 1.98 (m, 4H, 2 x CH 2‒CH2‒N), 1.32 (m, 6H, 2 x CH 3‒CH2‒O). 13C NMR (75 MHz, CDCl3): δ = 166.59 (d, 3 J PC = 20.1 Hz, ˭C‒C˭O), 153.82 (s, N‒C(O)‒N), 143.06 (d, 1 J PC = 198.9 Hz, C‒P), 105.57 (d, 2 J PC = 13.6 Hz, C˭C‒P), 63.28 (s, CH2‒O), 63.20 (s, CH2‒O), 46.75 (s, CH2‒N), 45.63 (s, CH2‒N), 36.51 (s, CH3‒N), 25.92 (s, CH2‒CH2‒N), 24.31 (s, CH2‒CH2‒N), 16.39 (s, CH3‒CH2‒O), 16.31 (s, CH3‒CH2‒O). 31P NMR (120 MHz, CDCl3): δ= 10.52. MS(EI): m/z (%) = 276 (M+-71, 18), 206 (22), 178 (25), 150 (55), 70 (100). Synthetic procedure for the preparation of ethyl 3-(diethoxyphosphoryl)-3-(3,3-dimethylureido)acrylate 13: To a stirred solution of oxazinone 1 (0.04 g, 0.14 mmol) in chloroform (5 mL), ethanol (0.05 g, 1 mmol) was added. The mixture was refluxed for 2 d, and the solvent removed by evaporation under reduced pressure. The crude product was purified by flash-column chromatography (silica gel, starting with AcOEt:Hex 10:50 and then AcOEt) to afford 13 (0.03 g, 67%) as a yellow oil. Selected data of 13: 1H NMR (300 MHz, CDCl3): δ = 11.20 (d, 3 J PH = 24.7 Hz, 1H, NH), 6.30 (d, 3 J PH = 16.2 Hz, 1H, HC˭C), 4.23 (m, 4H, 2 x CH2‒O‒P), 4.17 (q, 3 J HH = 7.2 Hz, 2H, CH2‒O‒CO), 3.11 (s, 3H, N‒CH3), 3.01 (s, 3H, N‒CH3), 1.36 (t, 3 J HH = 7.02 Hz, 6H, 2 x CH 3‒CH2‒O‒P), 1.26 (t, 3 J HH = 7.2 Hz, 3H, CH 3‒CH2‒O‒CO). 13C NMR (75 MHz, CDCl3): δ = 167.25 (d, 3 J PC = 20.1 Hz, ˭C‒C˭O), 152.31 (s, N‒C(O)‒N), 140.68 (d, 1 J PC = 197.9 Hz, C‒P), 107.00 (d, 2 J PC = 14.1 Hz, C˭C‒P), 63.37 (s, CH2‒O‒P), 63.29 (s, CH2‒O‒P), 61.68 (s, CH2‒O‒CO), 37.51 (s, CH3‒N), 35.40 (s, CH3‒N), 16.35 (s, CH3‒CH2‒O‒P), 16.27 (s, CH3‒CH2‒O‒P), 14.34 (s, CH3‒CH2‒O‒CO). 31P NMR (120 MHz, CDCl3): δ = 9.92. MS(EI): m/z (%) = 250 (M+-72, 11), 206 (56), 178 (32), 150 (100) ” .
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